Transition Metals and Virulence in Bacteria.

PubMed

Palmer, Lauren D; Skaar, Eric P

2016-11-23

Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies. Host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment of bacteria with toxic levels of metals. In response, bacteria have evolved systems to subvert metal sequestration and toxicity. The coevolution of hosts and their bacterial pathogens in the battle for metals has uncovered emerging paradigms in social microbiology, rapid evolution, host specificity, and metal homeostasis across domains. This review focuses on recent advances and open questions in our understanding of the complex role of transition metals at the host-pathogen interface.

Plague.

PubMed

Prentice, Michael B; Rahalison, Lila

2007-04-07

Bubonic plague is an often fulminant systemic zoonosis, caused by Yersinia pestis. Conventional microbiology, bacterial population genetics, and genome sequence data, all suggest that Y pestis is a recently evolved clone of the enteric pathogen Yersinia pseudotuberculosis. The genetic basis of this organism's rapid adaptation to its insect vector (the flea) with transmission between mammalian hosts by novel subcutaneous and pneumonic routes of infection is becoming clearer. This transition provides a paradigm for the way in which new pathogens could emerge. Plague in humans is controlled by suppression of rodent reservoir hosts and their fleas and by early detection and treatment of cases of disease. Detection systems for plague in non-endemic regions might now be needed because of a bioterrorism threat. Rapid diagnostic tests are available and a subunit vaccine is in clinical trials.

Natural selection promotes antigenic evolvability.

PubMed

Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

2013-01-01

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

Natural Selection Promotes Antigenic Evolvability

PubMed Central

Graves, Christopher J.; Ros, Vera I. D.; Stevenson, Brian; Sniegowski, Paul D.; Brisson, Dustin

2013-01-01

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed ‘cassettes’ that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections. PMID:24244173

Neutral Theory and Rapidly Evolving Viral Pathogens.

PubMed

Frost, Simon D W; Magalis, Brittany Rife; Kosakovsky Pond, Sergei L

2018-06-01

The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.

Deep sequencing of evolving pathogen populations: applications, errors, and bioinformatic solutions

PubMed Central

2014-01-01

Deep sequencing harnesses the high throughput nature of next generation sequencing technologies to generate population samples, treating information contained in individual reads as meaningful. Here, we review applications of deep sequencing to pathogen evolution. Pioneering deep sequencing studies from the virology literature are discussed, such as whole genome Roche-454 sequencing analyses of the dynamics of the rapidly mutating pathogens hepatitis C virus and HIV. Extension of the deep sequencing approach to bacterial populations is then discussed, including the impacts of emerging sequencing technologies. While it is clear that deep sequencing has unprecedented potential for assessing the genetic structure and evolutionary history of pathogen populations, bioinformatic challenges remain. We summarise current approaches to overcoming these challenges, in particular methods for detecting low frequency variants in the context of sequencing error and reconstructing individual haplotypes from short reads. PMID:24428920

The cell surface environment for pathogen recognition and entry.

PubMed

Stow, Jennifer L; Condon, Nicholas D

2016-04-01

The surface of mammalian cells offers an interface between the cell interior and its surrounding milieu. As part of the innate immune system, macrophages have cell surface features optimised for probing and sampling as they patrol our tissues for pathogens, debris or dead cells. Their highly dynamic and constantly moving cell surface has extensions such as lamellipodia, filopodia and dorsal ruffles that help detect pathogens. Dorsal ruffles give rise to macropinosomes for rapid, high volume non-selective fluid sampling, receptor internalisation and plasma membrane turnover. Ruffles can also generate phagocytic cups for the receptor-mediated uptake of pathogens or particles. The membrane lipids, actin cytoskeleton, receptors and signalling proteins that constitute these cell surface domains are discussed. Although the cell surface is designed to counteract pathogens, many bacteria, viruses and other pathogens have evolved to circumvent or hijack these cell structures and their underlying machinery for entry and survival. Nevertheless, these features offer important potential for developing vaccines, drugs and preventative measures to help fight infection.

Redefining disease emergence to improve prioritization and macro-ecological analyses.

PubMed

Rosenthal, Samantha R; Ostfeld, Richard S; McGarvey, Stephen T; Lurie, Mark N; Smith, Katherine F

2015-12-01

Microbial infections are as old as the hosts they sicken, but interest in the emergence of pathogens and the diseases they cause has been accelerating rapidly. The term 'emerging infectious disease' was coined in the mid-1900s to describe changes in disease dynamics in the modern era. Both the term and the phenomena it is meant to characterize have evolved and diversified over time, leading to inconsistencies and confusion. Here, we review the evolution of the term 'emerging infectious disease' (EID) in the literature as applied to human hosts. We examine the pathways (e.g., speciation or strain differentiation in the causative agent vs. rapid geographic expansion of an existing pathogen) by which diseases emerge. We propose a new framework for disease and pathogen emergence to improve prioritization. And we illustrate how the operational definition of an EID affects conclusions concerning the pathways by which diseases emerge and the ecological and socioeconomic drivers that elicit emergence. As EIDs appear to be increasing globally, and resources for science level off or decline, the research community is pushed to prioritize its focus on the most threatening diseases, riskiest potential pathogens, and the places they occur. The working definition of emerging infectious diseases and pathogens plays a crucial role in prioritization, but we argue that the current definitions may be impeding these efforts. We propose a new framework for classifying pathogens and diseases as "emerging" that distinguishes EIDs from emerging pathogens and novel potential pathogens. We suggest prioritization of: 1) EIDs for adaptation and mitigation, 2) emerging pathogens for preventive measures, and 3) novel potential pathogens for intensive surveillance.

Genes under positive selection in a model plant pathogenic fungus, Botrytis.

PubMed

Aguileta, Gabriela; Lengelle, Juliette; Chiapello, Hélène; Giraud, Tatiana; Viaud, Muriel; Fournier, Elisabeth; Rodolphe, François; Marthey, Sylvain; Ducasse, Aurélie; Gendrault, Annie; Poulain, Julie; Wincker, Patrick; Gout, Lilian

2012-07-01

The rapid evolution of particular genes is essential for the adaptation of pathogens to new hosts and new environments. Powerful methods have been developed for detecting targets of selection in the genome. Here we used divergence data to compare genes among four closely related fungal pathogens adapted to different hosts to elucidate the functions putatively involved in adaptive processes. For this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant species. A maximum likelihood-based analysis of 642 predicted orthologs detected 21 genes showing footprints of positive selection. These results were validated by resequencing nine of these genes in additional Botrytis species, showing they have also been rapidly evolving in other related species. Twenty of the 21 genes had not previously been identified as pathogenicity factors in B. cinerea, but some had functions related to plant-fungus interactions. The putative functions were involved in respiratory and energy metabolism, protein and RNA metabolism, signal transduction or virulence, similarly to what was detected in previous studies using the same approach in other pathogens. Mutants of B. cinerea were generated for four of these genes as a first attempt to elucidate their functions. Copyright © 2012 Elsevier B.V. All rights reserved.

The Staphylococcus aureus RNome and Its Commitment to Virulence

PubMed Central

Felden, Brice; Vandenesch, François; Bouloc, Philippe; Romby, Pascale

2011-01-01

Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity. PMID:21423670

Effector-triggered immunity: from pathogen perception to robust defense.

PubMed

Cui, Haitao; Tsuda, Kenichi; Parker, Jane E

2015-01-01

In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.

Post-translational regulation of plant immunity.

PubMed

Withers, John; Dong, Xinnian

2017-08-01

Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell. Recent studies focusing on deciphering post-translational mechanisms underlying plant immunity have offered an in-depth view of how PTMs facilitate efficient immune responses and have provided a more dynamic and holistic view of plant immunity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rapid evolution of avirulence genes in rice blast fungus Magnaporthe oryzae

PubMed Central

2014-01-01

Background Rice blast fungus Magnaporthe oryzae is one of the most devastating pathogens in rice. Avirulence genes in this fungus share a gene-for-gene relationship with the resistance genes in its host rice. Although numerous studies have shown that rice blast R-genes are extremely diverse and evolve rapidly in their host populations, little is known about the evolutionary patterns of the Avr-genes in the pathogens. Results Here, six well-characterized Avr-genes and seven randomly selected non-Avr control genes were used to investigate the genetic variations in 62 rice blast strains from different parts of China. Frequent presence/absence polymorphisms, high levels of nucleotide variation (~10-fold higher than non-Avr genes), high non-synonymous to synonymous substitution ratios, and frequent shared non-synonymous substitution were observed in the Avr-genes of these diversified blast strains. In addition, most Avr-genes are closely associated with diverse repeated sequences, which may partially explain the frequent presence/absence polymorphisms in Avr-genes. Conclusion The frequent deletion and gain of Avr-genes and rapid non-synonymous variations might be the primary mechanisms underlying rapid adaptive evolution of pathogens toward virulence to their host plants, and these features can be used as the indicators for identifying additional Avr-genes. The high number of nucleotide polymorphisms among Avr-gene alleles could also be used to distinguish genetic groups among different strains. PMID:24725999

Sexual Reproduction of Human Fungal Pathogens

PubMed Central

Heitman, Joseph; Carter, Dee A.; Dyer, Paul S.; Soll, David R.

2014-01-01

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms. PMID:25085958

Parallel evolution of a type IV secretion system in radiating lineages of the host-restricted bacterial pathogen Bartonella.

PubMed

Engel, Philipp; Salzburger, Walter; Liesch, Marius; Chang, Chao-Chin; Maruyama, Soichi; Lanz, Christa; Calteau, Alexandra; Lajus, Aurélie; Médigue, Claudine; Schuster, Stephan C; Dehio, Christoph

2011-02-10

Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment.

Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella

PubMed Central

Engel, Philipp; Salzburger, Walter; Liesch, Marius; Chang, Chao-Chin; Maruyama, Soichi; Lanz, Christa; Calteau, Alexandra; Lajus, Aurélie; Médigue, Claudine; Schuster, Stephan C.; Dehio, Christoph

2011-01-01

Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biological diversity by exploiting an exceptional range of environments, yet diversification of bacteria via adaptive radiation has been documented in a few cases only and the underlying molecular mechanisms are largely unknown. Here we show a compelling example of adaptive radiation in pathogenic bacteria and reveal their genetic basis. Our evolutionary genomic analyses of the α-proteobacterial genus Bartonella uncover two parallel adaptive radiations within these host-restricted mammalian pathogens. We identify a horizontally-acquired protein secretion system, which has evolved to target specific bacterial effector proteins into host cells as the evolutionary key innovation triggering these parallel adaptive radiations. We show that the functional versatility and adaptive potential of the VirB type IV secretion system (T4SS), and thereby translocated Bartonella effector proteins (Beps), evolved in parallel in the two lineages prior to their radiations. Independent chromosomal fixation of the virB operon and consecutive rounds of lineage-specific bep gene duplications followed by their functional diversification characterize these parallel evolutionary trajectories. Whereas most Beps maintained their ancestral domain constitution, strikingly, a novel type of effector protein emerged convergently in both lineages. This resulted in similar arrays of host cell-targeted effector proteins in the two lineages of Bartonella as the basis of their independent radiation. The parallel molecular evolution of the VirB/Bep system displays a striking example of a key innovation involved in independent adaptive processes and the emergence of bacterial pathogens. Furthermore, our study highlights the remarkable evolvability of T4SSs and their effector proteins, explaining their broad application in bacterial interactions with the environment. PMID:21347280

Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

PubMed Central

Lee, Dong-Hun; Bertran, Kateri; Kwon, Jung-Hoon

2017-01-01

Novel subtypes of Asian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4, such as H5N2, H5N5, H5N6, and H5N8, have been identified in China since 2008 and have since evolved into four genetically distinct clade 2.3.4.4 groups (A–D). Since 2014, HPAI clade 2.3.4.4 viruses have spread rapidly via migratory wild aquatic birds and have evolved through reassortment with prevailing local low pathogenicity avian influenza viruses. Group A H5N8 viruses and its reassortant viruses caused outbreaks in wide geographic regions (Asia, Europe, and North America) during 2014–2015. Novel reassortant Group B H5N8 viruses caused outbreaks in Asia, Europe, and Africa during 2016–2017. Novel reassortant Group C H5N6 viruses caused outbreaks in Korea and Japan during the 2016–2017 winter season. Group D H5N6 viruses caused outbreaks in China and Vietnam. A wide range of avian species, including wild and domestic waterfowl, domestic poultry, and even zoo birds, seem to be permissive for infection by and/or transmission of clade 2.3.4.4 HPAI viruses. Further, compared to previous H5N1 HPAI viruses, these reassortant viruses show altered pathogenicity in birds. In this review, we discuss the evolution, global spread, and pathogenicity of H5 clade 2.3.4.4 HPAI viruses. PMID:28859267

Conservation and Evolutionary Dynamics of the agr Cell-to-Cell Communication System across Firmicutes▿ †

PubMed Central

Wuster, Arthur; Babu, M. Madan

2008-01-01

We present evidence that the agr cell-to-cell communication system is present across firmicutes, including the human pathogen Clostridium perfringens. Although we find that the agr system is evolutionarily conserved and that the general functions which it regulates are similar in different species, the individual regulated genes are not the same. This suggests that the regulatory network controlled by agr is dynamic and evolves rapidly. PMID:17933897

NOD-like receptor cooperativity in effector-triggered immunity.

PubMed

Griebel, Thomas; Maekawa, Takaki; Parker, Jane E

2014-11-01

Intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are basic elements of innate immunity in plants and animals. Whereas animal NLRs react to conserved microbe- or damage-associated molecular patterns, plant NLRs intercept the actions of diverse pathogen virulence factors (effectors). In this review, we discuss recent genetic and molecular evidence for functional NLR pairs, and discuss the significance of NLR self-association and heteromeric NLR assemblies in the triggering of downstream signaling pathways. We highlight the versatility and impact of cooperating NLR pairs that combine pathogen sensing with the initiation of defense signaling in both plant and animal immunity. We propose that different NLR receptor molecular configurations provide opportunities for fine-tuning resistance pathways and enhancing the host's pathogen recognition spectrum to keep pace with rapidly evolving microbial populations. Copyright © 2014. Published by Elsevier Ltd.

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

PubMed Central

Hamede, Rodrigo K.; Pearse, Anne-Maree; Swift, Kate; Barmuta, Leon A.; Murchison, Elizabeth P.; Jones, Menna E.

2015-01-01

Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness. PMID:26336167

Two distinct classes of QTL determine rust resistance in sorghum.

PubMed

Wang, Xuemin; Mace, Emma; Hunt, Colleen; Cruickshank, Alan; Henzell, Robert; Parkes, Heidi; Jordan, David

2014-12-31

Agriculture is facing enormous challenges to feed a growing population in the face of rapidly evolving pests and pathogens. The rusts, in particular, are a major pathogen of cereal crops with the potential to cause large reductions in yield. Improving stable disease resistance is an on-going major and challenging focus for many plant breeding programs, due to the rapidly evolving nature of the pathogen. Sorghum is a major summer cereal crop that is also a host for a rust pathogen Puccinia purpurea, which occurs in almost all sorghum growing areas of the world, causing direct and indirect yield losses in sorghum worldwide, however knowledge about its genetic control is still limited. In order to further investigate this issue, QTL and association mapping methods were implemented to study rust resistance in three bi-parental populations and an association mapping set of elite breeding lines in different environments. In total, 64 significant or highly significant QTL and 21 suggestive rust resistance QTL were identified representing 55 unique genomic regions. Comparisons across populations within the current study and with rust QTL identified previously in both sorghum and maize revealed a high degree of correspondence in QTL location. Negative phenotypic correlations were observed between rust, maturity and height, indicating a trend for both early maturing and shorter genotypes to be more susceptible to rust. The significant amount of QTL co-location across traits, in addition to the consistency in the direction of QTL allele effects, has provided evidence to support pleiotropic QTL action across rust, height, maturity and stay-green, supporting the role of carbon stress in susceptibility to rust. Classical rust resistance QTL regions that did not co-locate with height, maturity or stay-green QTL were found to be significantly enriched for the defence-related NBS-encoding gene family, in contrast to the lack of defence-related gene enrichment in multi-trait effect rust resistance QTL. The distinction of disease resistance QTL hot-spots, enriched with defence-related gene families from QTL which impact on development and partitioning, provides plant breeders with knowledge which will allow for fast-tracking varieties with both durable pathogen resistance and appropriate adaptive traits.

Evolutionary relationships among pathogenic Candida species and relatives.

PubMed Central

Barns, S M; Lane, D J; Sogin, M L; Bibeau, C; Weisburg, W G

1991-01-01

Small subunit rRNA sequences have been determined for 10 of the most clinically important pathogenic species of the yeast genus Candida (including Torulopsis [Candida] glabrata and Yarrowia [Candida] lipolytica) and for Hansenula polymorpha. Phylogenetic analyses of these sequences and those of Saccharomyces cerevisiae, Kluyveromyces marxianus var. lactis, and Aspergillus fumigatus indicate that Candida albicans, C. tropicalis, C. parapsilosis, and C. viswanathii form a subgroup within the genus. The remaining significant pathogen, T. glabrata, falls into a second, distinct subgroup and is specifically related to S. cerevisiae and more distantly related to C. kefyr (psuedotropicalis) and K. marxianus var. lactis. The 18S rRNA sequence of Y. lipolytica has evolved rapidly in relation to the other Candida sequences examined and appears to be only distantly related to them. As anticipated, species of several other genera appear to bear specific relationships to members of the genus Candida. PMID:2007550

Sequence diversity and evolution of antimicrobial peptides in invertebrates.

PubMed

Tassanakajon, Anchalee; Somboonwiwat, Kunlaya; Amparyup, Piti

2015-02-01

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that act as the key components in the invertebrate innate immunity against invading pathogens. Several AMPs have been identified and characterized in invertebrates, and found to display considerable diversity in their amino acid sequence, structure and biological activity. AMP genes appear to have rapidly evolved, which might have arisen from the co-evolutionary arms race between host and pathogens, and enabled organisms to survive in different microbial environments. Here, the sequence diversity of invertebrate AMPs (defensins, cecropins, crustins and anti-lipopolysaccharide factors) are presented to provide a better understanding of the evolution pattern of these peptides that play a major role in host defense mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Pathogen-Host Interactions database (PHI-base): additions and future developments

PubMed Central

Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G.; Pedro, Helder; Hammond-Kosack, Kim E.

2015-01-01

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). PMID:25414340

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database--the quality controlled standard tool for routine identification of human and animal pathogenic fungi.

PubMed

Irinyi, Laszlo; Serena, Carolina; Garcia-Hermoso, Dea; Arabatzis, Michael; Desnos-Ollivier, Marie; Vu, Duong; Cardinali, Gianluigi; Arthur, Ian; Normand, Anne-Cécile; Giraldo, Alejandra; da Cunha, Keith Cassia; Sandoval-Denis, Marcelo; Hendrickx, Marijke; Nishikaku, Angela Satie; de Azevedo Melo, Analy Salles; Merseguel, Karina Bellinghausen; Khan, Aziza; Parente Rocha, Juliana Alves; Sampaio, Paula; da Silva Briones, Marcelo Ribeiro; e Ferreira, Renata Carmona; de Medeiros Muniz, Mauro; Castañón-Olivares, Laura Rosio; Estrada-Barcenas, Daniel; Cassagne, Carole; Mary, Charles; Duan, Shu Yao; Kong, Fanrong; Sun, Annie Ying; Zeng, Xianyu; Zhao, Zuotao; Gantois, Nausicaa; Botterel, Françoise; Robbertse, Barbara; Schoch, Conrad; Gams, Walter; Ellis, David; Halliday, Catriona; Chen, Sharon; Sorrell, Tania C; Piarroux, Renaud; Colombo, Arnaldo L; Pais, Célia; de Hoog, Sybren; Zancopé-Oliveira, Rosely Maria; Taylor, Maria Lucia; Toriello, Conchita; de Almeida Soares, Célia Maria; Delhaes, Laurence; Stubbe, Dirk; Dromer, Françoise; Ranque, Stéphane; Guarro, Josep; Cano-Lira, Jose F; Robert, Vincent; Velegraki, Aristea; Meyer, Wieland

2015-05-01

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rapid emergence of pathogens in agro-ecosystems: global threats to agricultural sustainability and food security.

PubMed

McDonald, Bruce A; Stukenbrock, Eva H

2016-12-05

Agricultural ecosystems are composed of genetically depauperate populations of crop plants grown at a high density and over large spatial scales, with the regional composition of crop species changing little from year to year. These environments are highly conducive for the emergence and dissemination of pathogens. The uniform host populations facilitate the specialization of pathogens to particular crop cultivars and allow the build-up of large population sizes. Population genetic and genomic studies have shed light on the evolutionary mechanisms underlying speciation processes, adaptive evolution and long-distance dispersal of highly damaging pathogens in agro-ecosystems. These studies document the speed with which pathogens evolve to overcome crop resistance genes and pesticides. They also show that crop pathogens can be disseminated very quickly across and among continents through human activities. In this review, we discuss how the peculiar architecture of agro-ecosystems facilitates pathogen emergence, evolution and dispersal. We present four example pathosystems that illustrate both pathogen specialization and pathogen speciation, including different time frames for emergence and different mechanisms underlying the emergence process. Lastly, we argue for a re-design of agro-ecosystems that embraces the concept of dynamic diversity to improve their resilience to pathogens. This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

Uncovering plant-pathogen crosstalk through apoplastic proteomic studies.

PubMed

Delaunois, Bertrand; Jeandet, Philippe; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan; Cordelier, Sylvain

2014-01-01

Plant pathogens have evolved by developing different strategies to infect their host, which in turn have elaborated immune responses to counter the pathogen invasion. The apoplast, including the cell wall and extracellular space outside the plasma membrane, is one of the first compartments where pathogen-host interaction occurs. The plant cell wall is composed of a complex network of polysaccharides polymers and glycoproteins and serves as a natural physical barrier against pathogen invasion. The apoplastic fluid, circulating through the cell wall and intercellular spaces, provides a means for delivering molecules and facilitating intercellular communications. Some plant-pathogen interactions lead to plant cell wall degradation allowing pathogens to penetrate into the cells. In turn, the plant immune system recognizes microbial- or damage-associated molecular patterns (MAMPs or DAMPs) and initiates a set of basal immune responses, including the strengthening of the plant cell wall. The establishment of defense requires the regulation of a wide variety of proteins that are involved at different levels, from receptor perception of the pathogen via signaling mechanisms to the strengthening of the cell wall or degradation of the pathogen itself. A fine regulation of apoplastic proteins is therefore essential for rapid and effective pathogen perception and for maintaining cell wall integrity. This review aims to provide insight into analyses using proteomic approaches of the apoplast to highlight the modulation of the apoplastic protein patterns during pathogen infection and to unravel the key players involved in plant-pathogen interaction.

Virus Satellites Drive Viral Evolution and Ecology

PubMed Central

Frígols, Belén; Quiles-Puchalt, Nuria; Mir-Sanchis, Ignacio; Donderis, Jorge; Elena, Santiago F.; Buckling, Angus; Novick, Richard P.; Marina, Alberto; Penadés, José R.

2015-01-01

Virus satellites are widespread subcellular entities, present both in eukaryotic and in prokaryotic cells. Their modus vivendi involves parasitism of the life cycle of their inducing helper viruses, which assures their transmission to a new host. However, the evolutionary and ecological implications of satellites on helper viruses remain unclear. Here, using staphylococcal pathogenicity islands (SaPIs) as a model of virus satellites, we experimentally show that helper viruses rapidly evolve resistance to their virus satellites, preventing SaPI proliferation, and SaPIs in turn can readily evolve to overcome phage resistance. Genomic analyses of both these experimentally evolved strains as well as naturally occurring bacteriophages suggest that the SaPIs drive the coexistence of multiple alleles of the phage-coded SaPI inducing genes, as well as sometimes selecting for the absence of the SaPI depressing genes. We report similar (accidental) evolution of resistance to SaPIs in laboratory phages used for Staphylococcus aureus typing and also obtain the same qualitative results in both experimental evolution and phylogenetic studies of Enterococcus faecalis phages and their satellites viruses. In summary, our results suggest that helper and satellite viruses undergo rapid coevolution, which is likely to play a key role in the evolution and ecology of the viruses as well as their prokaryotic hosts. PMID:26495848

Quorum quenching quandary: resistance to antivirulence compounds

PubMed Central

Maeda, Toshinari; García-Contreras, Rodolfo; Pu, Mingming; Sheng, Lili; Garcia, Luis Rene; Tomás, Maria; Wood, Thomas K

2012-01-01

Quorum sensing (QS) is the regulation of gene expression in response to the concentration of small signal molecules, and its inactivation has been suggested to have great potential to attenuate microbial virulence. It is assumed that unlike antimicrobials, inhibition of QS should cause less Darwinian selection pressure for bacterial resistance. Using the opportunistic pathogen Pseudomonas aeruginosa, we demonstrate here that bacterial resistance arises rapidly to the best-characterized compound that inhibits QS (brominated furanone C-30) due to mutations that increase the efflux of C-30. Critically, the C-30-resistant mutant mexR was more pathogenic to Caenorhabditis elegans in the presence of C-30, and the same mutation arises in bacteria responsible for chronic cystic fibrosis infections. Therefore, bacteria may evolve resistance to many new pharmaceuticals thought impervious to resistance. PMID:21918575

Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates

PubMed Central

Padler-Karavani, Vered; Hurtado-Ziola, Nancy; Chang, Yung-Chi; Sonnenburg, Justin L.; Ronaghy, Arash; Yu, Hai; Verhagen, Andrea; Nizet, Victor; Chen, Xi; Varki, Nissi; Varki, Ajit; Angata, Takashi

2014-01-01

Siglecs are sialic acid-binding Ig-like lectins that recognize sialoglycans via amino-terminal V-set domains. CD33-related Siglecs (CD33rSiglecs) on innate immune cells recognize endogenous sialoglycans as “self-associated molecular patterns” (SAMPs), dampening immune responses via cytosolic immunoreceptor tyrosine-based inhibition motifs that recruit tyrosine phosphatases. However, sialic acid-expressing pathogens subvert this mechanism through molecular mimicry. Meanwhile, endogenous host SAMPs must continually evolve to evade other pathogens that exploit sialic acids as invasion targets. We hypothesized that these opposing selection forces have accelerated CD33rSiglec evolution. We address this by comparative analysis of major CD33rSiglec (Siglec-3, Siglec-5, and Siglec-9) orthologs in humans, chimpanzees, and baboons. Recombinant soluble molecules displaying ligand-binding domains show marked quantitative and qualitative interspecies differences in interactions with strains of the sialylated pathogen, group B Streptococcus, and with sialoglycans presented as gangliosides or in the form of sialoglycan microarrays, including variations such as N-glycolyl and O-acetyl groups. Primate Siglecs also show quantitative and qualitative intra- and interspecies variations in expression patterns on leukocytes, both in circulation and in tissues. Taken together our data explain why the CD33rSiglec-encoding gene cluster is undergoing rapid evolution via multiple mechanisms, driven by the need to maintain self-recognition by innate immune cells, while escaping 2 distinct mechanisms of pathogen subversion.—Padler-Karavani, V., Hurtado-Ziola, N., Chang, Y.-C., Sonnenburg, J. L., Ronaghy, A., Yu, H., Verhagen, A., Nizet, V., Chen, X., Varki, N., Varki, A., Angata, T. Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. PMID:24308974

From perception to activation: the molecular-genetic and biochemical landscape of disease resistance signaling in plants.

PubMed

Knepper, Caleb; Day, Brad

2010-01-01

More than 60 years ago, H.H. Flor proposed the "Gene-for-Gene" hypothesis, which described the genetic relationship between host plants and pathogens. In the decades that followed Flor's seminal work, our understanding of the plant-pathogen interaction has evolved into a sophisticated model, detailing the molecular genetic and biochemical processes that control host-range, disease resistance signaling and susceptibility. The interaction between plants and microbes is an intimate exchange of signals that has evolved for millennia, resulting in the modification and adaptation of pathogen virulence strategies and host recognition elements. In total, plants have evolved mechanisms to combat the ever-changing landscape of biotic interactions bombarding their environment, while in parallel, plant pathogens have co-evolved mechanisms to sense and adapt to these changes. On average, the typical plant is susceptible to attack by dozens of microbial pathogens, yet in most cases, remains resistant to many of these challenges. The sum of research in our field has revealed that these interactions are regulated by multiple layers of intimately linked signaling networks. As an evolved model of Flor's initial observations, the current paradigm in host-pathogen interactions is that pathogen effector molecules, in large part, drive the recognition, activation and subsequent physiological responses in plants that give rise to resistance and susceptibility. In this Chapter, we will discuss our current understanding of the association between plants and microbial pathogens, detailing the pressures placed on both host and microbe to either maintain disease resistance, or induce susceptibility and disease. From recognition to transcriptional reprogramming, we will review current data and literature that has advanced the classical model of the Gene-for-Gene hypothesis to our current understanding of basal and effector triggered immunity.

The Pathogen-Host Interactions database (PHI-base): additions and future developments.

PubMed

Urban, Martin; Pant, Rashmi; Raghunath, Arathi; Irvine, Alistair G; Pedro, Helder; Hammond-Kosack, Kim E

2015-01-01

Rapidly evolving pathogens cause a diverse array of diseases and epidemics that threaten crop yield, food security as well as human, animal and ecosystem health. To combat infection greater comparative knowledge is required on the pathogenic process in multiple species. The Pathogen-Host Interactions database (PHI-base) catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and protist pathogens. Mutant phenotypes are associated with gene information. The included pathogens infect a wide range of hosts including humans, animals, plants, insects, fish and other fungi. The current version, PHI-base 3.6, available at http://www.phi-base.org, stores information on 2875 genes, 4102 interactions, 110 host species, 160 pathogenic species (103 plant, 3 fungal and 54 animal infecting species) and 181 diseases drawn from 1243 references. Phenotypic and gene function information has been obtained by manual curation of the peer-reviewed literature. A controlled vocabulary consisting of nine high-level phenotype terms permits comparisons and data analysis across the taxonomic space. PHI-base phenotypes were mapped via their associated gene information to reference genomes available in Ensembl Genomes. Virulence genes and hotspots can be visualized directly in genome browsers. Future plans for PHI-base include development of tools facilitating community-led curation and inclusion of the corresponding host target(s). © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity.

PubMed

Brüssow, Harald

2007-08-01

Bacteriophages and protists are major causes of bacterial mortality. Genomics suggests that phages evolved well before eukaryotic protists. Bacteria were thus initially only confronted with phage predators. When protists evolved, bacteria were caught between two types of predators. One successful antigrazing strategy of bacteria was the elaboration of toxins that would kill the grazer. The released cell content would feed bystander bacteria. I suggest here that, to fight grazing protists, bacteria teamed up with those phage predators that concluded at least a temporary truce with them in the form of lysogeny. Lysogeny was perhaps initially a resource management strategy of phages that could not maintain infection chains. Subsequently, lysogeny might have evolved into a bacterium-prophage coalition attacking protists, which became a food source for them. When protists evolved into multicellular animals, the lysogenic bacteria tracked their evolving food source. This hypothesis could explain why a frequent scheme of bacterial pathogenicity is the survival in phagocytes, why a significant fraction of bacterial pathogens have prophage-encoded virulence genes, and why some virulence factors of animal pathogens are active against unicellular eukaryotes. Bacterial pathogenicity might thus be one playing option of the stone-scissor-paper game played between phages-bacteria-protists, with humans getting into the crossfire.

Comparative genome analysis of rice-pathogenic Burkholderia provides insight into capacity to adapt to different environments and hosts.

PubMed

Seo, Young-Su; Lim, Jae Yun; Park, Jungwook; Kim, Sunyoung; Lee, Hyun-Hee; Cheong, Hoon; Kim, Sang-Mok; Moon, Jae Sun; Hwang, Ingyu

2015-05-06

In addition to human and animal diseases, bacteria of the genus Burkholderia can cause plant diseases. The representative species of rice-pathogenic Burkholderia are Burkholderia glumae, B. gladioli, and B. plantarii, which primarily cause grain rot, sheath rot, and seedling blight, respectively, resulting in severe reductions in rice production. Though Burkholderia rice pathogens cause problems in rice-growing countries, comprehensive studies of these rice-pathogenic species aiming to control Burkholderia-mediated diseases are only in the early stages. We first sequenced the complete genome of B. plantarii ATCC 43733T. Second, we conducted comparative analysis of the newly sequenced B. plantarii ATCC 43733T genome with eleven complete or draft genomes of B. glumae and B. gladioli strains. Furthermore, we compared the genome of three rice Burkholderia pathogens with those of other Burkholderia species such as those found in environmental habitats and those known as animal/human pathogens. These B. glumae, B. gladioli, and B. plantarii strains have unique genes involved in toxoflavin or tropolone toxin production and the clustered regularly interspaced short palindromic repeats (CRISPR)-mediated bacterial immune system. Although the genome of B. plantarii ATCC 43733T has many common features with those of B. glumae and B. gladioli, this B. plantarii strain has several unique features, including quorum sensing and CRISPR/CRISPR-associated protein (Cas) systems. The complete genome sequence of B. plantarii ATCC 43733T and publicly available genomes of B. glumae BGR1 and B. gladioli BSR3 enabled comprehensive comparative genome analyses among three rice-pathogenic Burkholderia species responsible for tissue rotting and seedling blight. Our results suggest that B. glumae has evolved rapidly, or has undergone rapid genome rearrangements or deletions, in response to the hosts. It also, clarifies the unique features of rice pathogenic Burkholderia species relative to other animal and human Burkholderia species.

Human infection with highly pathogenic H5N1 influenza virus.

PubMed

Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro

2008-04-26

Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

Bacterial Cytological Profiling (BCP) as a Rapid and Accurate Antimicrobial Susceptibility Testing Method for Staphylococcus aureus.

PubMed

Quach, D T; Sakoulas, G; Nizet, V; Pogliano, J; Pogliano, K

2016-02-01

Successful treatment of bacterial infections requires the timely administration of appropriate antimicrobial therapy. The failure to initiate the correct therapy in a timely fashion results in poor clinical outcomes, longer hospital stays, and higher medical costs. Current approaches to antibiotic susceptibility testing of cultured pathogens have key limitations ranging from long run times to dependence on prior knowledge of genetic mechanisms of resistance. We have developed a rapid antimicrobial susceptibility assay for Staphylococcus aureus based on bacterial cytological profiling (BCP), which uses quantitative fluorescence microscopy to measure antibiotic induced changes in cellular architecture. BCP discriminated between methicillin-susceptible (MSSA) and -resistant (MRSA) clinical isolates of S. aureus (n = 71) within 1-2 h with 100% accuracy. Similarly, BCP correctly distinguished daptomycin susceptible (DS) from daptomycin non-susceptible (DNS) S. aureus strains (n = 20) within 30 min. Among MRSA isolates, BCP further identified two classes of strains that differ in their susceptibility to specific combinations of beta-lactam antibiotics. BCP provides a rapid and flexible alternative to gene-based susceptibility testing methods for S. aureus, and should be readily adaptable to different antibiotics and bacterial species as new mechanisms of resistance or multidrug-resistant pathogens evolve and appear in mainstream clinical practice.

Tailored immune responses: novel effector helper T cell subsets in protective immunity.

PubMed

Kara, Ervin E; Comerford, Iain; Fenix, Kevin A; Bastow, Cameron R; Gregor, Carly E; McKenzie, Duncan R; McColl, Shaun R

2014-02-01

Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

Drug resistance in eukaryotic microorganisms

PubMed Central

Fairlamb, Alan H.; Gow, Neil A. R.; Matthews, Keith R.; Waters, Andrew P.

2016-01-01

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies. PMID:27572976

Population Genetic Analysis Infers Migration Pathways of Phytophthora ramorum in US Nurseries

PubMed Central

Goss, Erica M.; Larsen, Meg; Chastagner, Gary A.; Givens, Donald R.; Grünwald, Niklaus J.

2009-01-01

Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in the late 1990s, that is responsible for sudden oak death in California forests and ramorum blight of common ornamentals. The nursery trade has moved this pathogen from source populations on the West Coast to locations across the United States, thus risking introduction to other native forests. We examined the genetic diversity of P. ramorum in United States nurseries by microsatellite genotyping 279 isolates collected from 19 states between 2004 and 2007. Of the three known P. ramorum clonal lineages, the most common and genetically diverse lineage in the sample was NA1. Two eastward migration pathways were revealed in the clustering of NA1 isolates into two groups, one containing isolates from Connecticut, Oregon, and Washington and the other isolates from California and the remaining states. This finding is consistent with trace forward analyses conducted by the US Department of Agriculture's Animal and Plant Health Inspection Service. At the same time, genetic diversities in several states equaled those observed in California, Oregon, and Washington and two-thirds of multilocus genotypes exhibited limited geographic distributions, indicating that mutation was common during or subsequent to migration. Together, these data suggest that migration, rapid mutation, and genetic drift all play a role in structuring the genetic diversity of P. ramorum in US nurseries. This work demonstrates that fast-evolving genetic markers can be used to examine the evolutionary processes acting on recently introduced pathogens and to infer their putative migration patterns, thus showing promise for the application of forensics to plant pathogens. PMID:19774068

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

PubMed Central

Lo, Chien-Chi; Bonner, Carol A.

2012-01-01

Summary: One form of immune evasion is a developmental state called “persistence” whereby chlamydial pathogens respond to the host-mediated withdrawal of l-tryptophan (Trp). A sophisticated survival mode of reversible quiescence is implemented. A mechanism has evolved which suppresses gene products necessary for rapid pathogen proliferation but allows expression of gene products that underlie the morphological and developmental characteristics of persistence. This switch from one translational profile to an alternative translational profile of newly synthesized proteins is proposed to be accomplished by maximizing the Trp content of some proteins needed for rapid proliferation (e.g., ADP/ATP translocase, hexose-phosphate transporter, phosphoenolpyruvate [PEP] carboxykinase, the Trp transporter, the Pmp protein superfamily for cell adhesion and antigenic variation, and components of the cell division pathway) while minimizing the Trp content of other proteins supporting the state of persistence. The Trp starvation mechanism is best understood in the human-Chlamydia trachomatis relationship, but the similarity of up-Trp and down-Trp proteomic profiles in all of the pathogenic Chlamydiaceae suggests that Trp availability is an underlying cue relied upon by this family of pathogens to trigger developmental transitions. The biochemically expensive pathogen strategy of selectively increased Trp usage to guide the translational profile can be leveraged significantly with minimal overall Trp usage by (i) regional concentration of Trp residue placements, (ii) amplified Trp content of a single protein that is required for expression or maturation of multiple proteins with low Trp content, and (iii) Achilles'-heel vulnerabilities of complex pathways to high Trp content of one or a few enzymes. PMID:22688818

Synthetic Biology in Cell and Organ Transplantation.

PubMed

Stevens, Sean

2017-02-01

The transplantation of cells and organs has an extensive history, with blood transfusion and skin grafts described as some of the earliest medical interventions. The speed and efficiency of the human immune system evolved to rapidly recognize and remove pathogens; the human immune system also serves as a barrier against the transplant of cells and organs from even highly related donors. Although this shows the remarkable effectiveness of the immune system, the engineering of cells and organs that will survive in a host patient over the long term remains a steep challenge. Progress in the understanding of host immune responses to donor cells and organs, combined with the rapid advancement in synthetic biology applications, allows the rational engineering of more effective solutions for transplantation. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Protection of turmeric plants from rhizome rot disease under field conditions by β-D-glucan nanoparticle.

PubMed

Anusuya, Sathiyanarayanan; Sathiyabama, Muthukrishnan

2015-01-01

The rhizome rot caused by Pythium aphanidermatum is one of the most devastating diseases of the turmeric crop. Fungicides are unable to control the rapidly evolving P. aphanidermatum and new control strategies are urgently needed. This study examined the effect of β-d-glucan nanoparticles (GNP) in turmeric plants under field condition by the foliar spray method. Enhanced plant growth, rhizome yield, and curcumin content demonstrate the positive effect of the GNP on turmeric plants. Rapid activation of various defense enzymes was also observed in leaves and rhizomes of treated plants. GNP-treated plants showed a decreased rot incidence. It may be possible that increased defense enzymes might have played a role in reducing the colonization of pathogen. Copyright © 2015 Elsevier B.V. All rights reserved.

Overcoming antibiotic resistance: Is siderophore Trojan horse conjugation an answer to evolving resistance in microbial pathogens?

PubMed

Dhusia, Kalyani; Bajpai, Archana; Ramteke, P W

2018-01-10

Comparative study of siderophore biosynthesis pathway in pathogens provides potential targets for antibiotics and host drug delivery as a part of computationally feasible microbial therapy. Iron acquisition using siderophore models is an essential and well established model in all microorganisms and microbial infections a known to cause great havoc to both plant and animal. Rapid development of antibiotic resistance in bacterial as well as fungal pathogens has drawn us at a verge where one has to get rid of the traditional way of obstructing pathogen using single or multiple antibiotic/chemical inhibitors or drugs. 'Trojan horse' strategy is an answer to this imperative call where antibiotic are by far sneaked into the pathogenic cell via the siderophore receptors at cell and outer membrane. This antibiotic once gets inside, generates a 'black hole' scenario within the opportunistic pathogens via iron scarcity. For pathogens whose siderophore are not compatible to smuggle drug due to their complex conformation and stiff valence bonds, there is another approach. By means of the siderophore biosynthesis pathways, potential targets for inhibition of these siderophores in pathogenic bacteria could be achieved and thus control pathogenic virulence. Method to design artificial exogenous siderophores for pathogens that would compete and succeed the battle of intake is also covered with this review. These manipulated siderophore would enter pathogenic cell like any other siderophore but will not disperse iron due to which iron inadequacy and hence pathogens control be accomplished. The aim of this review is to offer strategies to overcome the microbial infections/pathogens using siderophore. Copyright © 2017 Elsevier B.V. All rights reserved.

Pivoting the Plant Immune System from Dissection to Deployment

PubMed Central

Dangl, Jeffery L.; Horvath, Diana M.; Staskawicz, Brian J.

2013-01-01

Diverse and rapidly evolving pathogens cause plant diseases and epidemics that threaten crop yield and food security around the world. Research over the last 25 years has led to an increasingly clear conceptual understanding of the molecular components of the plant immune system. Combined with ever-cheaper DNA-sequencing technology and the rich diversity of germ plasm manipulated for over a century by plant breeders, we now have the means to begin development of durable (long-lasting) disease resistance beyond the limits imposed by conventional breeding and in a manner that will replace costly and unsustainable chemical controls. PMID:23950531

The maintenance of sex: Ronald Fisher meets the Red Queen.

PubMed

Green, David; Mason, Chris

2013-08-21

Sex in higher diploids carries a two-fold cost of males that should reduce its fitness relative to cloning, and result in its extinction. Instead, sex is widespread and clonal species face early obsolescence. One possible reason is that sex is an adaptation that allows organisms to respond more effectively to endless changes in their environment. The purpose of this study was to model mutation and selection in a diploid organism in an evolving environment and ascertain their support for sex. We used a computational approach to model finite populations where a haploid environment subjects a diploid host to endlessly evolving change. Evolution in both populations is primarily through adoption of novel advantageous mutations within a large allele space. Sex outcompetes cloning by two complementary mechanisms. First, sexual diploids adopt advantageous homozygous mutations more rapidly than clonal ones under conditions of lag load (the gap between the actual adaptation of the diploid population and its theoretical optimum). This rate advantage can offset the higher fecundity of cloning. Second, a relative advantage to sex emerges where populations are significantly polymorphic, because clonal polymorphism runs the risk of clonal interference caused by selection on numerous lines of similar adaptation. This interference extends allele lifetime and reduces the rate of adaptation. Sex abolishes the interference, making selection faster and elevating population fitness. Differences in adaptation between sexual and clonal populations increase markedly with the number of loci under selection, the rate of mutation in the host, and a rapidly evolving environment. Clonal interference in these circumstances leads to conditions where the greater fecundity of clones is unable to offset their poor adaptation. Sexual and clonal populations then either co-exist, or sex emerges as the more stable evolutionary strategy. Sex can out-compete clones in a rapidly evolving environment, such as that characterized by pathogens, where clonal interference reduces the adaptation of clonal populations and clones adopt advantageous mutations more slowly. Since all organisms carry parasitic loads, the model is of potentially general applicability.

Development of novel vaccines using DNA shuffling and screening strategies.

PubMed

Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

2004-02-01

DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

Evolution of eukaryotic microbial pathogens via covert sexual reproduction

PubMed Central

Heitman, Joseph

2010-01-01

Sexual reproduction enables eukaryotic organisms to re-assort genetic diversity and purge deleterious mutations, producing better-fit progeny. Sex arose early and pervades eukaryotes. Fungal and parasite pathogens once thought asexual have maintained cryptic sexual cycles, including unisexual or parasexual reproduction. As pathogens become niche and host-adapted, sex appears to specialize to promote inbreeding and clonality yet maintain out-crossing potential. During self-fertile sexual modes, sex itself may generate genetic diversity de novo. Mating-type loci govern fungal sexual identity; how parasites establish sexual identity is unknown. Comparing and contrasting fungal and parasite sex promises to reveal how microbial pathogens evolved and are evolving. PMID:20638645

Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection.

PubMed

Schlaberg, Robert; Chiu, Charles Y; Miller, Steve; Procop, Gary W; Weinstock, George

2017-06-01

- Metagenomic sequencing can be used for detection of any pathogens using unbiased, shotgun next-generation sequencing (NGS), without the need for sequence-specific amplification. Proof-of-concept has been demonstrated in infectious disease outbreaks of unknown causes and in patients with suspected infections but negative results for conventional tests. Metagenomic NGS tests hold great promise to improve infectious disease diagnostics, especially in immunocompromised and critically ill patients. - To discuss challenges and provide example solutions for validating metagenomic pathogen detection tests in clinical laboratories. A summary of current regulatory requirements, largely based on prior guidance for NGS testing in constitutional genetics and oncology, is provided. - Examples from 2 separate validation studies are provided for steps from assay design, and validation of wet bench and bioinformatics protocols, to quality control and assurance. - Although laboratory and data analysis workflows are still complex, metagenomic NGS tests for infectious diseases are increasingly being validated in clinical laboratories. Many parallels exist to NGS tests in other fields. Nevertheless, specimen preparation, rapidly evolving data analysis algorithms, and incomplete reference sequence databases are idiosyncratic to the field of microbiology and often overlooked.

Mediated Plastid RNA Editing in Plant Immunity

PubMed Central

García-Andrade, Javier; Ramírez, Vicente; López, Ana; Vera, Pablo

2013-01-01

Plant regulatory circuits coordinating nuclear and plastid gene expression have evolved in response to external stimuli. RNA editing is one of such control mechanisms. We determined the Arabidopsis nuclear-encoded homeodomain-containing protein OCP3 is incorporated into the chloroplast, and contributes to control over the extent of ndhB transcript editing. ndhB encodes the B subunit of the chloroplast NADH dehydrogenase-like complex (NDH) involved in cyclic electron flow (CEF) around photosystem I. In ocp3 mutant strains, ndhB editing efficiency decays, CEF is impaired and disease resistance to fungal pathogens substantially enhanced, a process recapitulated in plants defective in editing plastid RNAs encoding NDH complex subunits due to mutations in previously described nuclear-encoded pentatricopeptide-related proteins (i.e. CRR21, CRR2). Furthermore, we observed that following a pathogenic challenge, wild type plants respond with editing inhibition of ndhB transcript. In parallel, rapid destabilization of the plastidial NDH complex is also observed in the plant following perception of a pathogenic cue. Therefore, NDH complex activity and plant immunity appear as interlinked processes. PMID:24204264

Editorial: Biological Engagement Programs: Reducing Threats and Strengthening Global Health Security Through Scientific Collaboration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fair, Jeanne M.

It is often said about infectious diseases that a “threat anywhere is a threat everywhere,” and the recent outbreaks of Ebola in West Africa and Zika virus in South America have proven that pathogens know no borders. Not only are they transboundary, pathogens do not discriminate who they infect. In addition to the natural increase in emerging zoonotic infectious diseases worldwide due to changing environmental conditions and globalization, the use of infectious diseases as warfare agents is a threat in today’s world. Early detection remains one of the best ways to prevent small outbreaks becoming epidemics and pandemics. We findmore » that an accurate diagnosis, detection, and reporting of diseases are important components of mitigating outbreaks, and biosurveillance remains the top tool in our toolbox. And while vaccines have been important for controlling more common infectious virus diseases, they are less feasible for less common diseases, emerging pathogens, and rapidly evolving microbes. Furthermore, due to globalization and increased travel, emigration, and migration, biosurveillance is critical throughout the world, not just in pockets of more developed regions.« less

Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

PubMed Central

Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard

2017-01-01

Abstract Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host–pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID:26857943

Editorial: Biological Engagement Programs: Reducing Threats and Strengthening Global Health Security Through Scientific Collaboration

DOE PAGES

Fair, Jeanne M.

2017-07-12

It is often said about infectious diseases that a “threat anywhere is a threat everywhere,” and the recent outbreaks of Ebola in West Africa and Zika virus in South America have proven that pathogens know no borders. Not only are they transboundary, pathogens do not discriminate who they infect. In addition to the natural increase in emerging zoonotic infectious diseases worldwide due to changing environmental conditions and globalization, the use of infectious diseases as warfare agents is a threat in today’s world. Early detection remains one of the best ways to prevent small outbreaks becoming epidemics and pandemics. We findmore » that an accurate diagnosis, detection, and reporting of diseases are important components of mitigating outbreaks, and biosurveillance remains the top tool in our toolbox. And while vaccines have been important for controlling more common infectious virus diseases, they are less feasible for less common diseases, emerging pathogens, and rapidly evolving microbes. Furthermore, due to globalization and increased travel, emigration, and migration, biosurveillance is critical throughout the world, not just in pockets of more developed regions.« less

The conservation relevance of epidemiological research into carnivore viral diseases in the serengeti.

PubMed

Cleaveland, Sarah; Mlengeya, Titus; Kaare, Magai; Haydon, Dan; Lembo, Tiziana; Laurenson, M Karen; Packer, Craig

2007-06-01

Recent outbreaks of rabies and canine distemper in wildlife populations of the Serengeti show that infectious disease constitutes a significant cause of mortality that can result in regional extirpation of endangered species even within large, well-protected areas. Nevertheless, effective management of an infectious disease depends critically on understanding the epidemiological dynamics of the causative pathogen. Pathogens with short infection cycles cannot persist in small populations in the absence of a more permanent reservoir of infection. Development of appropriate interventions requires detailed data on transmission pathways between reservoirs and wildlife populations of conservation concern. Relevant data can be derived from long-term population monitoring, epidemic and case-surveillance patterns, genetic analyses of rapidly evolving pathogens, serological surveys, and intervention studies. We examined studies of carnivore diseases in the Serengeti. Epidemiological research contributes to wildlife conservation policy in terms of management of endangered populations and the integration of wildlife conservation with public health interventions. Long-term, integrative, cross-species research is essential for formulation of effective policy for disease control and optimization of ecosystem health.

Use of high-throughput mass spectrometry to elucidate host pathogen interactions in Salmonella

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodland, Karin D.; Adkins, Joshua N.; Ansong, Charles

Capabilities in mass spectrometry are evolving rapidly, with recent improvements in sensitivity, data analysis, and most important, from the standpoint of this review, much higher throughput allowing analysis of many samples in a single day. This short review describes how these improvements in mass spectrometry can be used to dissect host-pathogen interactions using Salmonella as a model system. This approach enabled direct identification of the majority of annotated Salmonella proteins, quantitation of expression changes under various in vitro growth conditions, and new insights into virulence and expression of Salmonella proteins within host cell cells. One of the most significant findingsmore » is that a very high percentage of the all annotated genes (>20%) in Salmonella are regulated post-transcriptionally. In addition, new and unexpected interactions have been identified for several Salmonella virulence regulators that involve protein-protein interactions, suggesting additional functions of these regulators in coordinating virulence expression. Overall high throughput mass spectrometry provides a new view of pathogen-host interactions emphasizing the protein products and defining how protein interactions determine the outcome of infection.« less

Successive increases in the resistance of Drosophila to viral infection through a transposon insertion followed by a Duplication.

PubMed

Magwire, Michael M; Bayer, Florian; Webster, Claire L; Cao, Chuan; Jiggins, Francis M

2011-10-01

To understand the molecular basis of how hosts evolve resistance to their parasites, we have investigated the genes that cause variation in the susceptibility of Drosophila melanogaster to viral infection. Using a host-specific pathogen of D. melanogaster called the sigma virus (Rhabdoviridae), we mapped a major-effect polymorphism to a region containing two paralogous genes called CHKov1 and CHKov2. In a panel of inbred fly lines, we found that a transposable element insertion in the protein coding sequence of CHKov1 is associated with increased resistance to infection. Previous research has shown that this insertion results in a truncated messenger RNA that encodes a far shorter protein than the susceptible allele. This resistant allele has rapidly increased in frequency under directional selection and is now the commonest form of the gene in natural populations. Using genetic mapping and site-specific recombination, we identified a third genotype with considerably greater resistance that is currently rare in the wild. In these flies there have been two duplications, resulting in three copies of both the truncated allele of CHKov1 and CHKov2 (one of which is also truncated). Remarkably, the truncated allele of CHKov1 has previously been found to confer resistance to organophosphate insecticides. As estimates of the age of this allele predate the use of insecticides, it is likely that this allele initially functioned as a defence against viruses and fortuitously "pre-adapted" flies to insecticides. These results demonstrate that strong selection by parasites for increased host resistance can result in major genetic changes and rapid shifts in allele frequencies; and, contrary to the prevailing view that resistance to pathogens can be a costly trait to evolve, the pleiotropic effects of these changes can have unexpected benefits.

The Battle for Iron between Humans and Microbes.

PubMed

Carver, Peggy L

2018-01-01

Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Notable Aspects of Glycan-Protein Interactions

PubMed Central

Cohen, Miriam

2015-01-01

This mini review highlights several interesting aspects of glycan-mediated interactions that are common between cells, bacteria, and viruses. Glycans are ubiquitously found on all living cells, and in the extracellular milieu of multicellular organisms. They are known to mediate initial binding and recognition events of both immune cells and pathogens with their target cells or tissues. The host target tissues are hidden under a layer of secreted glycosylated decoy targets. In addition, pathogens can utilize and display host glycans to prevent identification as foreign by the host’s immune system (molecular mimicry). Both the host and pathogens continually evolve. The host evolves to prevent infection and the pathogens evolve to evade host defenses. Many pathogens express both glycan-binding proteins and glycosidases. Interestingly, these proteins are often located at the tip of elongated protrusions in bacteria, or in the leading edge of the cell. Glycan-protein interactions have low affinity and, as a result, multivalent interactions are often required to achieve biologically relevant binding. These enable dynamic forms of adhesion mechanisms, reviewed here, and include rolling (cells), stick and roll (bacteria) or surfacing (viruses). PMID:26340640

Independently evolved virulence effectors converge onto hubs in a plant immune system network.

PubMed

Mukhtar, M Shahid; Carvunis, Anne-Ruxandra; Dreze, Matija; Epple, Petra; Steinbrenner, Jens; Moore, Jonathan; Tasan, Murat; Galli, Mary; Hao, Tong; Nishimura, Marc T; Pevzner, Samuel J; Donovan, Susan E; Ghamsari, Lila; Santhanam, Balaji; Romero, Viviana; Poulin, Matthew M; Gebreab, Fana; Gutierrez, Bryan J; Tam, Stanley; Monachello, Dario; Boxem, Mike; Harbort, Christopher J; McDonald, Nathan; Gai, Lantian; Chen, Huaming; He, Yijian; Vandenhaute, Jean; Roth, Frederick P; Hill, David E; Ecker, Joseph R; Vidal, Marc; Beynon, Jim; Braun, Pascal; Dangl, Jeffery L

2011-07-29

Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.

Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

PubMed Central

2012-01-01

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection. PMID:22647543

Epigenetics and Therapeutic Targets Mediating Neuroprotection

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. PMID:26236020

Arabidopsis histone methyltransferase SET DOMAIN GROUP8 mediates induction of the jasmonate/ethylene pathway genes in plant defense response to necrotrophic fungi.

PubMed

Berr, Alexandre; McCallum, Emily J; Alioua, Abdelmalek; Heintz, Dimitri; Heitz, Thierry; Shen, Wen-Hui

2010-11-01

As sessile organisms, plants have to endure a wide variety of biotic and abiotic stresses, and accordingly they have evolved intricate and rapidly inducible defense strategies associated with the activation of a battery of genes. Among other mechanisms, changes in chromatin structure are thought to provide a flexible, global, and stable means for the regulation of gene transcription. In support of this idea, we demonstrate here that the Arabidopsis (Arabidopsis thaliana) histone methyltransferase SET DOMAIN GROUP8 (SDG8) plays a crucial role in plant defense against fungal pathogens by regulating a subset of genes within the jasmonic acid (JA) and/or ethylene signaling pathway. We show that the loss-of-function mutant sdg8-1 displays reduced resistance to the necrotrophic fungal pathogens Alternaria brassicicola and Botrytis cinerea. While levels of JA, a primary phytohormone involved in plant defense, and camalexin, a major phytoalexin against fungal pathogens, remain unchanged or even above normal in sdg8-1, induction of several defense genes within the JA/ethylene signaling pathway is severely compromised in response to fungal infection or JA treatment in mutant plants. Both downstream genes and, remarkably, also upstream mitogen-activated protein kinase kinase genes MKK3 and MKK5 are misregulated in sdg8-1. Accordingly, chromatin immunoprecipitation analysis shows that sdg8-1 impairs dynamic changes of histone H3 lysine 36 methylation at defense marker genes as well as at MKK3 and MKK5, which normally occurs upon infection with fungal pathogens or methyl JA treatment in wild-type plants. Our data indicate that SDG8-mediated histone H3 lysine 36 methylation may serve as a memory of permissive transcription for a subset of defense genes, allowing rapid establishment of transcriptional induction.

Evolution of Drosophila resistance against different pathogens and infection routes entails no detectable maintenance costs.

PubMed

Faria, Vítor G; Martins, Nelson E; Paulo, Tânia; Teixeira, Luís; Sucena, Élio; Magalhães, Sara

2015-11-01

Pathogens exert a strong selective pressure on hosts, entailing host adaptation to infection. This adaptation often affects negatively other fitness-related traits. Such trade-offs may underlie the maintenance of genetic diversity for pathogen resistance. Trade-offs can be tested with experimental evolution of host populations adapting to parasites, using two approaches: (1) measuring changes in immunocompetence in relaxed-selection lines and (2) comparing life-history traits of evolved and control lines in pathogen-free environments. Here, we used both approaches to examine trade-offs in Drosophila melanogaster populations evolving for over 30 generations under infection with Drosophila C Virus or the bacterium Pseudomonas entomophila, the latter through different routes. We find that resistance is maintained after up to 30 generations of relaxed selection. Moreover, no differences in several classical life-history traits between control and evolved populations were found in pathogen-free environments, even under stresses such as desiccation, nutrient limitation, and high densities. Hence, we did not detect any maintenance costs associated with resistance to pathogens. We hypothesize that extremely high selection pressures commonly used lead to the disproportionate expression of costs relative to their actual occurrence in natural systems. Still, the maintenance of genetic variation for pathogen resistance calls for an explanation. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Evolution of the rodent eosinophil-associated RNase gene family by rapid gene sorting and positive selection

PubMed Central

Zhang, Jianzhi; Dyer, Kimberly D.; Rosenberg, Helene F.

2000-01-01

The mammalian RNase A superfamily comprises a diverse array of ribonucleolytic proteins that have a variety of biochemical activities and physiological functions. Two rapidly evolving RNases of higher primates are of particular interest as they are major secretory proteins of eosinophilic leukocytes and have been found to possess anti-pathogen activities in vitro. To understand how these RNases acquired this function during evolution and to develop animal models for the study of their functions in vivo, it is necessary to investigate these genes in many species. Here, we report the sequences of 38 functional genes and 23 pseudogenes of the eosinophil-associated RNase (EAR) family from 5 rodent species. Our phylogenetic analysis of these genes showed a clear pattern of evolution by a rapid birth-and-death process and gene sorting, a process characterized by rapid gene duplication and deactivation occurring differentially among lineages. This process ultimately generates distinct or only partially overlapping inventories of the genes, even in closely related species. Positive Darwinian selection also contributed to the diversification of these EAR genes. The striking similarity between the evolutionary patterns of the EAR genes and those of the major histocompatibility complex, immunoglobulin, and T cell receptor genes stands in strong support of the hypothesis that host-defense and generation of diversity are among the primary physiological function of the rodent EARs. The discovery of a large number of divergent EARs suggests the intriguing possibility that these proteins have been specifically tailored to fight against distinct rodent pathogens. PMID:10758160

Spatial variation in disease resistance: from molecules to metapopulations

PubMed Central

Laine, Anna-Liisa; Burdon, Jeremy J.; Dodds, Peter N.; Thrall, Peter H.

2010-01-01

Summary Variation in disease resistance is a widespread phenomenon in wild plant-pathogen associations. Here, we review current literature on natural plant-pathogen associations to determine how diversity in disease resistance is distributed at different hierarchical levels – within host individuals, within host populations, among host populations at the metapopulation scale and at larger regional scales. We find diversity in resistance across all spatial scales examined. Furthermore, variability seems to be the best counter-defence of plants against their rapidly evolving pathogens. We find that higher diversity of resistance phenotypes also results in higher levels of resistance at the population level. Overall, we find that wild plant populations are more likely to be susceptible than resistant to their pathogens. However, the degree of resistance differs strikingly depending on the origin of the pathogen strains used in experimental inoculation studies. Plant populations are on average 16% more resistant to allopatric pathogen strains than they are to strains that occur within the same population (48 % vs. 32 % respectively). Pathogen dispersal mode affects levels of resistance in natural plant populations with lowest levels detected for hosts of airborne pathogens and highest for waterborne pathogens. Detailed analysis of two model systems, Linum marginale infected by Melampsora lini, and Plantago lanceolata infected by Podosphaera plantaginis, show that the amount of variation in disease resistance declines towards higher spatial scales as we move from individual hosts to metapopulations, but evaluation of multiple spatial scales is needed to fully capture the structure of disease resistance. Synthesis: Variation in disease resistance is ubiquitous in wild plant-pathogen associations. While the debate over whether the resistance structure of plant populations is determined by pathogen-imposed selection versus non-adaptive processes remains unresolved, we do report examples of pathogen-imposed selection on host resistance. Here we highlight the importance of measuring resistance across multiple spatial scales, and of using sympatric strains when looking for signs of coevolution in wild plant-pathogen interactions. PMID:21243068

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae

PubMed Central

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition. PMID:28400786

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae.

PubMed

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition.

Museum samples reveal rapid evolution by wild honey bees exposed to a novel parasite

PubMed Central

Mikheyev, Alexander S.; Tin, Mandy M. Y.; Arora, Jatin; Seeley, Thomas D.

2015-01-01

Understanding genetic changes caused by novel pathogens and parasites can reveal mechanisms of adaptation and genetic robustness. Using whole-genome sequencing of museum and modern specimens, we describe the genomic changes in a wild population of honey bees in North America following the introduction of the ectoparasitic mite, Varroa destructor. Even though colony density in the study population is the same today as in the past, a major loss of haplotypic diversity occurred, indicative of a drastic mitochondrial bottleneck, caused by massive colony mortality. In contrast, nuclear genetic diversity did not change, though hundreds of genes show signs of selection. The genetic diversity within each bee colony, particularly as a consequence of polyandry by queens, may enable preservation of genetic diversity even during population bottlenecks. These findings suggest that genetically diverse honey bee populations can recover from introduced diseases by evolving rapid tolerance, while maintaining much of the standing genetic variation. PMID:26246313

Museum samples reveal rapid evolution by wild honey bees exposed to a novel parasite.

PubMed

Mikheyev, Alexander S; Tin, Mandy M Y; Arora, Jatin; Seeley, Thomas D

2015-08-06

Understanding genetic changes caused by novel pathogens and parasites can reveal mechanisms of adaptation and genetic robustness. Using whole-genome sequencing of museum and modern specimens, we describe the genomic changes in a wild population of honey bees in North America following the introduction of the ectoparasitic mite, Varroa destructor. Even though colony density in the study population is the same today as in the past, a major loss of haplotypic diversity occurred, indicative of a drastic mitochondrial bottleneck, caused by massive colony mortality. In contrast, nuclear genetic diversity did not change, though hundreds of genes show signs of selection. The genetic diversity within each bee colony, particularly as a consequence of polyandry by queens, may enable preservation of genetic diversity even during population bottlenecks. These findings suggest that genetically diverse honey bee populations can recover from introduced diseases by evolving rapid tolerance, while maintaining much of the standing genetic variation.

A brief history of vaccines: smallpox to the present.

PubMed

Hsu, Jennifer L

2013-01-01

Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

Site-Specific Editing of the Plasmodium falciparum Genome Using Engineered Zinc-Finger Nucleases

PubMed Central

Straimer, Judith; Lee, Marcus CS; Lee, Andrew H; Zeitler, Bryan; Williams, April E; Pearl, Jocelynn R; Zhang, Lei; Rebar, Edward J; Gregory, Philip D; Llinás, Manuel; Urnov, Fyodor D; Fidock, David A

2013-01-01

Malaria afflicts over 200 million people worldwide and its most lethal etiologic agent, Plasmodium falciparum, is evolving to resist even the latest-generation therapeutics. Efficient tools for genome-directed investigations of P. falciparum pathogenesis, including drug resistance mechanisms, are clearly required. Here we report rapid and targeted genetic engineering of this parasite, using zinc-finger nucleases (ZFNs) that produce a double-strand break in a user-defined locus and trigger homology-directed repair. Targeting an integrated egfp locus, we obtained gene deletion parasites with unprecedented speed (two weeks), both with and without direct selection. ZFNs engineered against the endogenous parasite gene pfcrt, responsible for chloroquine treatment escape, rapidly produced parasites that carried either an allelic replacement or a panel of specified point mutations. The efficiency, versatility and precision of this method will enable a diverse array of genome editing approaches to interrogate this human pathogen. PMID:22922501

Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later

PubMed Central

Pittock, Sean J.; Lucchinetti, Claudia F.

2015-01-01

The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4) as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease, has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging (MRI) brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO-IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin-4 channelopathy. PMID:26096370

Vibrio parahaemolyticus Strains of Pandemic Serotypes Identified from Clinical and Environmental Samples from Jiangsu, China

PubMed Central

Li, Jingjiao; Xue, Feng; Yang, Zhenquan; Zhang, Xiaoping; Zeng, Dexin; Chao, Guoxiang; Jiang, Yuan; Li, Baoguang

2016-01-01

Vibrio parahaemolyticus has emerged as a major foodborne pathogen in China, Japan, Thailand, and other Asian countries. In this study, 72 strains of V. parahaemolyticus were isolated from clinical and environmental samples between 2006 and 2014 in Jiangsu, China. The serotypes and six virulence genes including thermostable direct hemolysin (TDR) and TDR-related hemolysin (TRH) genes were assessed among the isolates. Twenty five serotypes were identified and O3:K6 was one of the dominant serotypes. The genetic diversity was assessed by multilocus sequence typing (MLST) analysis, and 48 sequence types (STs) were found, suggesting this V. parahaemolyticus group is widely dispersed and undergoing rapid evolution. A total of 25 strains of pandemic serotypes such as O3:K6, O5:K17, and O1:KUT were identified. It is worth noting that the pandemic serotypes were not exclusively identified from clinical samples, rather, nine strains were also isolated from environmental samples; and some of these strains harbored several virulence genes, which may render those strains pathogenicity potential. Therefore, the emergence of these “environmental” pandemic V. parahaemolyticus strains may poses a new threat to the public health in China. Furthermore, six novel serotypes and 34 novel STs were identified among the 72 isolates, indicating that V. parahaemolyticus were widely distributed and fast evolving in the environment in Jiangsu, China. The findings of this study provide new insight into the phylogenic relationship between V. parahaemolyticus strains of pandemic serotypes from clinical and environmental sources and enhance the MLST database; and our proposed possible O- and K- antigen evolving paths of V. parahaemolyticus may help understand how the serotypes of this dispersed bacterial population evolve. PMID:27303379

Rapid Evolution and the Importance of Recombination to the Gastroenteric Pathogen Campylobacter jejuni

PubMed Central

Gabriel, Edith; Leatherbarrow, Andrew J.H.; Cheesbrough, John; Gee, Steven; Bolton, Eric; Fox, Andrew; Hart, C. Anthony; Diggle, Peter J.; Fearnhead, Paul

2009-01-01

Responsible for the majority of bacterial gastroenteritis in the developed world, Campylobacter jejuni is a pervasive pathogen of humans and animals, but its evolution is obscure. In this paper, we exploit contemporary genetic diversity and empirical evidence to piece together the evolutionary history of C. jejuni and quantify its evolutionary potential. Our combined population genetics–phylogenetics approach reveals a surprising picture. Campylobacter jejuni is a rapidly evolving species, subject to intense purifying selection that purges 60% of novel variation, but possessing a massive evolutionary potential. The low mutation rate is offset by a large effective population size so that a mutation at any site can occur somewhere in the population within the space of a week. Recombination has a fundamental role, generating diversity at twice the rate of de novo mutation, and facilitating gene flow between C. jejuni and its sister species Campylobacter coli. We attempt to calibrate the rate of molecular evolution in C. jejuni based solely on within-species variation. The rates we obtain are up to 1,000 times faster than conventional estimates, placing the C. jejuni–C. coli split at the time of the Neolithic revolution. We weigh the plausibility of such recent bacterial evolution against alternative explanations and discuss the evidence required to settle the issue. PMID:19008526

Comparative genomics using microarrays reveals divergence and loss of virulence-associated genes in host-specific strains of the insect pathogen Metarhizium anisopliae.

PubMed

Wang, Sibao; Leclerque, Andreas; Pava-Ripoll, Monica; Fang, Weiguo; St Leger, Raymond J

2009-06-01

Many strains of Metarhizium anisopliae have broad host ranges, but others are specialists and adapted to particular hosts. Patterns of gene duplication, divergence, and deletion in three generalist and three specialist strains were investigated by heterologous hybridization of genomic DNA to genes from the generalist strain Ma2575. As expected, major life processes are highly conserved, presumably due to purifying selection. However, up to 7% of Ma2575 genes were highly divergent or absent in specialist strains. Many of these sequences are conserved in other fungal species, suggesting that there has been rapid evolution and loss in specialist Metarhizium genomes. Some poorly hybridizing genes in specialists were functionally coordinated, indicative of reductive evolution. These included several involved in toxin biosynthesis and sugar metabolism in root exudates, suggesting that specialists are losing genes required to live in alternative hosts or as saprophytes. Several components of mobile genetic elements were also highly divergent or lost in specialists. Exceptionally, the genome of the specialist cricket pathogen Ma443 contained extra insertion elements that might play a role in generating evolutionary novelty. This study throws light on the abundance of orphans in genomes, as 15% of orphan sequences were found to be rapidly evolving in the Ma2575 lineage.

Antagonistic Activity of Nocardia brasiliensis PTCC 1422 Against Isolated Enterobacteriaceae from Urinary Tract Infections.

PubMed

Jalali, Hossnieh Kafshdar; Salamatzadeh, Abdolreza; Jalali, Arezou Kafshdar; Kashani, Hamed Haddad; Asbchin, Salman Ahmadi; Issazadeh, Khosro

2016-03-01

The main drawback of current antibiotic therapies is the emergence and rapid increase in antibiotic resistance. Nocardiae are aerobic, Gram-positive, catalase-positive, non-motile actinomycetes. Nocardia brasiliensis was reported as antibiotic producer. The purpose of the study was to determine antibacterial activity of N. brasiliensis PTCC 1422 against isolated Enterobacteriaceae from urinary tract infections (UTIs). The common bacteria from UTIs were isolated from hospital samples. Antimicrobial susceptibility test was performed for the isolated pathogens using Kirby-Bauer disk diffusion method according to clinical and Laboratory Standards Institute guideline. Antagonistic activity of N. brasiliensis PTCC 1422 was examined with well diffusion methods. Supernatant of N. brasiliensis PTCC 1422 by submerged culture was analyzed with gas chromatography-mass spectrometry. Isolated strains included Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Proteus mirabilis. The most common pathogen isolated was E. coli (72.5%). Bacterial isolates revealed the presence of high levels of antimicrobial resistances to ceftriaxone and low levels of resistance to cephalexin. Supernatant of N. brasiliensis PTCC 1422 showed antibacterial activity against all of the isolated microorganisms in well diffusion method. The antibiotic resistance among the uropathogens is an evolving process, so a routine surveillance to monitor the etiologic agents of UTI and the resistance pattern should be carried out timely to choose the most effective empirical treatment by the physicians. Our present investigation indicates that the substances present in the N. brasiliensis PTCC 1422 could be used to inhibit the growth of human pathogen. Antibacterial resistance among bacterial uropathogen is an evolving process. Therefore, in the field on the need of re-evaluation of empirical treatment of UTIs, our present. The study has demonstrated that N. brasiliensis PTCC 1422 has a high potential for the treatment of UTIs.

Dominant integration locus drives continuous diversification of plant immune receptors with exogenous domain fusions.

PubMed

Bailey, Paul C; Schudoma, Christian; Jackson, William; Baggs, Erin; Dagdas, Gulay; Haerty, Wilfried; Moscou, Matthew; Krasileva, Ksenia V

2018-02-19

The plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes. We show that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events reveals that homologous receptors can be fused to diverse domains. Furthermore, we discover a 43 amino acid long motif associated with this dominant integration clade which is located immediately upstream of the fusion site. Sequence analysis reveals that DNA transposition and/or ectopic recombination are the most likely mechanisms of formation for nucleotide binding leucine rich repeat proteins with integrated domains. The identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen "baits."

Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy

PubMed Central

Ganesan, Raja; Hos, Nina Judith; Gutierrez, Saray; Fischer, Julia; Stepek, Joanna Magdalena; Daglidu, Evmorphia; Krönke, Martin

2017-01-01

During intracellular infections, autophagy significantly contributes to the elimination of pathogens, regulation of pro-inflammatory signaling, secretion of immune mediators and in coordinating the adaptive immune system. Intracellular pathogens such as S. Typhimurium have evolved mechanisms to circumvent autophagy. However, the regulatory mechanisms targeted by S. Typhimurium to modulate autophagy have not been fully resolved. Here we report that cytosolic energy loss during S. Typhimurium infection triggers transient activation of AMPK, an important checkpoint of mTOR activity and autophagy. The activation of AMPK is regulated by LKB1 in a cytosolic complex containing Sirt1 and LKB1, where Sirt1 is required for deacetylation and subsequent activation of LKB1. S. Typhimurium infection targets Sirt1, LKB1 and AMPK to lysosomes for rapid degradation resulting in the disruption of the AMPK-mediated regulation of mTOR and autophagy. The degradation of cytosolic Sirt1/LKB1/AMPK complex was not observed with two mutant strains of S. Typhimurium, ΔssrB and ΔssaV, both compromising the pathogenicity island 2 (SPI2). The results highlight virulence factor-dependent degradation of host cell proteins as a previously unrecognized strategy of S. Typhimurium to evade autophagy. PMID:28192515

Virulence and pathogen multiplication: a serial passage experiment in the hypervirulent bacterial insect-pathogen Xenorhabdus nematophila.

PubMed

Chapuis, Élodie; Pagès, Sylvie; Emelianoff, Vanya; Givaudan, Alain; Ferdy, Jean-Baptiste

2011-01-31

The trade-off hypothesis proposes that the evolution of pathogens' virulence is shaped by a link between virulence and contagiousness. This link is often assumed to come from the fact that pathogens are contagious only if they can reach high parasitic load in the infected host. In this paper we present an experimental test of the hypothesis that selection on fast replication can affect virulence. In a serial passage experiment, we selected 80 lines of the bacterial insect-pathogen Xenorhabdus nematophila to multiply fast in an artificial culture medium. This selection resulted in shortened lag phase in our selected bacteria. We then injected these bacteria into insects and observed an increase in virulence. This could be taken as a sign that virulence in Xenorhabdus is linked to fast multiplication. But we found, among the selected lineages, either no link or a positive correlation between lag duration and virulence: the most virulent bacteria were the last to start multiplying. We then surveyed phenotypes that are under the control of the flhDC super regulon, which has been shown to be involved in Xenorhabdus virulence. We found that, in one treatment, the flhDC regulon has evolved rapidly, but that the changes we observed were not connected to virulence. All together, these results indicate that virulence is, in Xenorhabdus as in many other pathogens, a multifactorial trait. Being able to grow fast is one way to be virulent. But other ways exist which renders the evolution of virulence hard to predict.

Role of India's wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications.

PubMed

Singh, B B; Gajadhar, A A

2014-10-01

Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India. Copyright © 2014 Elsevier B.V. All rights reserved.

Plant immunity: unravelling the complexity of plant responses to biotic stresses.

PubMed

Miller, Robert Neil Gerard; Costa Alves, Gabriel Sergio; Van Sluys, Marie-Anne

2017-03-01

Plants are constantly exposed to evolving pathogens and pests, with crop losses representing a considerable threat to global food security. As pathogen evolution can overcome disease resistance that is conferred by individual plant resistance genes, an enhanced understanding of the plant immune system is necessary for the long-term development of effective disease management strategies. Current research is rapidly advancing our understanding of the plant innate immune system, with this multidisciplinary subject area reflected in the content of the 18 papers in this Special Issue. Advances in specific areas of plant innate immunity are highlighted in this issue, with focus on molecular interactions occurring between plant hosts and viruses, bacteria, phytoplasmas, oomycetes, fungi, nematodes and insect pests. We provide a focus on research across multiple areas related to pathogen sensing and plant immune response. Topics covered are categorized as follows: binding proteins in plant immunity; cytokinin phytohormones in plant growth and immunity; plant-virus interactions; plant-phytoplasma interactions; plant-fungus interactions; plant-nematode interactions; plant immunity in Citrus; plant peptides and volatiles; and assimilate dynamics in source/sink metabolism. Although knowledge of the plant immune system remains incomplete, the considerable ongoing scientific progress into pathogen sensing and plant immune response mechanisms suggests far reaching implications for the development of durable disease resistance against pathogens and pests. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Rapid evolution of PARP genes suggests a broad role for ADP-ribosylation in host-virus conflicts.

PubMed

Daugherty, Matthew D; Young, Janet M; Kerns, Julie A; Malik, Harmit S

2014-01-01

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic 'arms races' with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in 'housekeeping' functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.

Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts

PubMed Central

Daugherty, Matthew D.; Young, Janet M.; Kerns, Julie A.; Malik, Harmit S.

2014-01-01

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts. PMID:24875882

When are pathogen genome sequences informative of transmission events?

PubMed Central

Ferguson, Neil; Jombart, Thibaut

2018-01-01

Recent years have seen the development of numerous methodologies for reconstructing transmission trees in infectious disease outbreaks from densely sampled whole genome sequence data. However, a fundamental and as of yet poorly addressed limitation of such approaches is the requirement for genetic diversity to arise on epidemiological timescales. Specifically, the position of infected individuals in a transmission tree can only be resolved by genetic data if mutations have accumulated between the sampled pathogen genomes. To quantify and compare the useful genetic diversity expected from genetic data in different pathogen outbreaks, we introduce here the concept of ‘transmission divergence’, defined as the number of mutations separating whole genome sequences sampled from transmission pairs. Using parameter values obtained by literature review, we simulate outbreak scenarios alongside sequence evolution using two models described in the literature to describe transmission divergence of ten major outbreak-causing pathogens. We find that while mean values vary significantly between the pathogens considered, their transmission divergence is generally very low, with many outbreaks characterised by large numbers of genetically identical transmission pairs. We describe the impact of transmission divergence on our ability to reconstruct outbreaks using two outbreak reconstruction tools, the R packages outbreaker and phybreak, and demonstrate that, in agreement with previous observations, genetic sequence data of rapidly evolving pathogens such as RNA viruses can provide valuable information on individual transmission events. Conversely, sequence data of pathogens with lower mean transmission divergence, including Streptococcus pneumoniae, Shigella sonnei and Clostridium difficile, provide little to no information about individual transmission events. Our results highlight the informational limitations of genetic sequence data in certain outbreak scenarios, and demonstrate the need to expand the toolkit of outbreak reconstruction tools to integrate other types of epidemiological data. PMID:29420641

The multigenic nature of the differences in pathogenicity of H5N1 highly pathogenic avian influenza viruses in domestic ducks

USDA-ARS?s Scientific Manuscript database

The Eurasian H5N1 highly pathogenic avian influenza (HPAI) viruses have evolved into many genetic lineages. The divergent strains that have arisen express distinct pathobiological features and increased virulence for many bird species including domestic waterfowl. The pathogenicity of H5N1 HPAI vi...

Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction.

PubMed

Brocca-Cofano, Egidio; Kuhrt, David; Siewe, Basile; Xu, Cuiling; Haret-Richter, George S; Craigo, Jodi; Labranche, Celia; Montefiori, David C; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

2017-12-01

We compared and contrasted pathogenic (in pig-tailed macaques [PTMs]) and nonpathogenic (in African green monkeys [AGMs]) SIVsab infections to assess the significance of the B cell dysfunction observed in simian (SIV) and human immunodeficiency virus (HIV) infections. We report that the loss of B cells is specifically associated with the pathogenic SIV infection, while in the natural hosts, in which SIV is nonpathogenic, B cells rapidly increase in both lymph nodes (LNs) and intestine. SIV-associated B cell dysfunction associated with the pathogenic SIV infection is characterized by loss of naive B cells, loss of resting memory B cells due to their redistribution to the gut, increases of the activated B cells and circulating tissue-like memory B cells, and expansion of the B regulatory cells (Bregs). While circulating B cells are virtually restored to preinfection levels during the chronic pathogenic SIV infection, restoration is mainly due to an expansion of the "exhausted," virus-specific B cells, i.e., activated memory cells and tissue-like memory B cells. Despite of the B cell dysfunction, SIV-specific antibody (Ab) production was higher in the PTMs than in AGMs, with the caveat that rapid disease progression in PTMs was strongly associated with lack of anti-SIV Ab. Neutralization titers and the avidity and maturation of immune responses did not differ between pathogenic and nonpathogenic infections, with the exception of the conformational epitope recognition, which evolved from low to high conformations in the natural host. The patterns of humoral immune responses in the natural host are therefore more similar to those observed in HIV-infected subjects, suggesting that natural hosts may be more appropriate for modeling the immunization strategies aimed at preventing HIV disease progression. The numerous differences between the pathogenic and nonpathogenic infections with regard to dynamics of the memory B cell subsets point to their role in the pathogenesis of HIV/SIV infections and suggest that monitoring B cells may be a reliable approach for assessing disease progression. IMPORTANCE We report here that the HIV/SIV-associated B cell dysfunction (defined by loss of total and memory B cells, increased B regulatory cell [Breg] counts, and B cell activation and apoptosis) is specifically associated with pathogenic SIV infection and absent during the course of nonpathogenic SIV infection in natural nonhuman primate hosts. Alterations of the B cell population are not correlated with production of neutralizing antibodies, the levels of which are similar in the two species. Rapid progressive infections are associated with a severe impairment in SIV-specific antibody production. While we did not find major differences in avidity and maturation between the pathogenic and nonpathogenic SIV infections, we identified a major difference in conformational epitope recognition, with the nonpathogenic infection being characterized by an evolution from low to high conformations. B cell dysfunction should be considered in designing immunization strategies aimed at preventing HIV disease progression. Copyright © 2017 American Society for Microbiology.

Evolution of N-species Kimura/voter models towards criticality, a surrogate for general models of accidental pathogens

NASA Astrophysics Data System (ADS)

Ghaffari, Peyman; Stollenwerk, Nico

2012-09-01

In models for accidental pathogens, with the paradigmatic epidemiological system of bacterial meningitis, there was evolution towards states exhibiting critical fluctuations with power law behaviour observed [1]. This is a model with many possibly pathogenic strains essentially evolving independently to low pathogenicity. A first and previous study had shown that in the limit of vanishing pathogenicity there are critical fluctuations with power law distributions observed, already when only two strains interact [2]. This earlier version of a two strain model was very recently reinvestigated [3] and named as Stollenwerk-Jansen model (SJ). Muñoz et al. demonstrated that this two-strain model for accidental pathogens is in the universality class of the so-called voter model. Though this model clearly shows criticality, its control parameter, the pathogenicity, is not self-tuning towards criticality. However, the multi-strain version mentioned above [1] is well evolving towards criticality, as well as a spatially explicit version of this, shown in [4] p. 155. These models of multi-strain type including explicitly mutations of the pathogenicity can be called SJ-models of type II [5]. Since the original epidemiological model is of SIRYX-type, the evolution to zero pathogenicity is slow and perturbed by large population noise. In the present article we now show on the basis of the notion of the voter-model universality classes the evolution of n-voter models with mutaion towards criticality, now much less perturbed by population noise, hence demonstrating a clear mechanism of self-organized criticality in the sense of [6, 7]. The present results have wide implications for many diseases in which a large proportion of infections is asymptomatic, meaning that the system has already evolved towards an average low pathogenicity. This holds not only for the original paradigmatic case of bacterial meningitis, but was reecently also suggested for example for dengue fever (DENFREE project).

Host shifts result in parallel genetic changes when viruses evolve in closely related species

PubMed Central

Day, Jonathan P.; Smith, Sophia C. L.; Houslay, Thomas M.; Tagliaferri, Lucia

2018-01-01

Host shifts, where a pathogen invades and establishes in a new host species, are a major source of emerging infectious diseases. They frequently occur between related host species and often rely on the pathogen evolving adaptations that increase their fitness in the novel host species. To investigate genetic changes in novel hosts, we experimentally evolved replicate lineages of an RNA virus (Drosophila C Virus) in 19 different species of Drosophilidae and deep sequenced the viral genomes. We found a strong pattern of parallel evolution, where viral lineages from the same host were genetically more similar to each other than to lineages from other host species. When we compared viruses that had evolved in different host species, we found that parallel genetic changes were more likely to occur if the two host species were closely related. This suggests that when a virus adapts to one host it might also become better adapted to closely related host species. This may explain in part why host shifts tend to occur between related species, and may mean that when a new pathogen appears in a given species, closely related species may become vulnerable to the new disease. PMID:29649296

Guiding the evolution to catch the virus: An in silico study of affinity maturation against rapidly mutating antigen

NASA Astrophysics Data System (ADS)

Wang, Shenshen; Burton, Dennis; Kardar, Mehran; Chakraborty, Arup

2014-03-01

The immune system comprises an intricate and evolving collection of cells and molecules that enables a defense against pathogenic agents. Its workings present a rich source of physical problems that impact human health. One intriguing example is the process of affinity maturation (AM) through which an antibody (Ab)--a component of the host immune system--evolves to more efficiently bind an antigen (Ag)--a unique part of a foreign pathogen such as a virus. Sufficiently strong binding to the Ag enables recognition and neutralization. A major challenge is to contain a diversifying mixture of Ag variants, that arise in natural infection, from evading Ab neutralization. This entails a thorough understanding of AM against multiple Ag species and mutating Ag. During AM, Ab-encoding cells undergo cycles of mutation and selection, a process reminiscent of Darwinian evolution yet occurring in real time. We first cast affinity-dependent selection into an extreme value problem and show how the binding characteristics scale with Ag diversity. We then develop an agent-based residue-resolved computational model of AM which allows us to track the evolutionary trajectories of individual cells. This dynamic model not only reveals significant stochastic effects associated with the relatively small and highly dynamic population size, it also uncovers the markedly distinct maturation outcomes if designed Ag variants are presented in different temporal procedures. Insights thus obtained would guide rational design of vaccination protocols.

Immune genes and divergent antimicrobial peptides in flies of the subgenus Drosophila.

PubMed

Hanson, Mark A; Hamilton, Phineas T; Perlman, Steve J

2016-10-24

Drosophila is an important model for studying the evolution of animal immunity, due to the powerful genetic tools developed for D. melanogaster. However, Drosophila is an incredibly speciose lineage with a wide range of ecologies, natural histories, and diverse natural enemies. Surprisingly little functional work has been done on immune systems of species other than D. melanogaster. In this study, we examine the evolution of immune genes in the speciose subgenus Drosophila, which diverged from the subgenus Sophophora (that includes D. melanogaster) approximately 25-40 Mya. We focus on D. neotestacea, a woodland species used to study interactions between insects and parasitic nematodes, and combine recent transcriptomic data with infection experiments to elucidate aspects of host immunity. We found that the vast majority of genes involved in the D. melanogaster immune response are conserved in D. neotestacea, with a few interesting exceptions, particularly in antimicrobial peptides (AMPs); until recently, AMPs were not thought to evolve rapidly in Drosophila. Unexpectedly, we found a distinct diptericin in subgenus Drosophila flies that appears to have evolved under diversifying (positive) selection. We also describe the presence of the AMP drosocin, which was previously thought to be restricted to the subgenus Sophophora, in the subgenus Drosophila. We challenged two subgenus Drosophila species, D. neotestacea and D. virilis with bacterial and fungal pathogens and quantified AMP expression. While diptericin in D. virilis was induced by exposure to gram-negative bacteria, it was not induced in D. neotestacea, showing that conservation of immune genes does not necessarily imply conservation of the realized immune response. Our study lends support to the idea that invertebrate AMPs evolve rapidly, and that Drosophila harbor a diverse repertoire of AMPs with potentially important functional consequences.

Prediction of molecular mimicry candidates in human pathogenic bacteria.

PubMed

Doxey, Andrew C; McConkey, Brendan J

2013-08-15

Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria.

Prediction of molecular mimicry candidates in human pathogenic bacteria

PubMed Central

Doxey, Andrew C; McConkey, Brendan J

2013-01-01

Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria. PMID:23715053

Sexually transmitted infection and the evolution of serial monogamy

PubMed Central

McLeod, David V.; Day, Troy

2014-01-01

The selective forces shaping mating systems have long been of interest to biologists. One particular selective pressure that has received comparatively little attention is sexually transmitted infections (STIs). While it has been hypothesized that STIs could drive the evolutionary emergence of monogamy, there is little theoretical support. Here we use an evolutionary invasion analysis to determine what aspects of pathogen virulence and transmission are necessary for serial monogamy to evolve in a promiscuous population. We derive a biologically intuitive invasion condition in terms of population-specific quantities. From this condition, we obtain two main results. First, when pathogen virulence causes mortality rather than sterility, monogamy is more likely to evolve. Second, we find that at intermediate pathogen transmission rates, monogamy is the most selectively advantageous, whereas at high- and low-transmission rates, monogamy is generally selected against. As a result, it is possible for a pathogen to be highly virulent, yet for promiscuity to persist. PMID:25320174

Significance and integration of molecular diagnostics in the framework of veterinary practice.

PubMed

Aranaz, Alicia

2015-01-01

The field of molecular diagnostics in veterinary practice is rapidly evolving. An array of molecular techniques of different complexity is available to facilitate the fast and specific diagnosis of animal diseases. The choice for the adequate technique is dependent on the mission and attributions of the laboratory and requires both a knowledge of the molecular biology basis and of its limitations. The ability to quickly detect pathogens and their characteristics would allow for precise decision-making and target measures such as prophylaxis, appropriate therapy, and biosafety plans to control disease outbreaks. In practice, taking benefit of the huge amount of data that can be obtained using molecular techniques highlights the need of collaboration between veterinarians in the laboratory and practitioners.

Epigenetics and therapeutic targets mediating neuroprotection.

PubMed

Qureshi, Irfan A; Mehler, Mark F

2015-12-02

The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.

PubMed

Lachance, Claude; Gottschalk, Marcelo; Gerber, Pehuén P; Lemire, Paul; Xu, Jianguo; Segura, Mariela

2013-06-01

Streptococcus suis, a major porcine pathogen, can be transmitted to humans and cause severe symptoms. A large human outbreak associated with an unusual streptococcal toxic shock-like syndrome (STSLS) was described in China. Albeit an early burst of proinflammatory cytokines following Chinese S. suis infection was suggested to be responsible for STSLS case severity, the mechanisms involved are still poorly understood. Using a mouse model, the host response to S. suis infection with a North American intermediately pathogenic strain, a European highly pathogenic strain, and the Chinese epidemic strain was investigated by a whole-genome microarray approach. Proinflammatory genes were expressed at higher levels in mice infected with the Chinese strain than those infected with the European strain. The Chinese strain induced a fast and strong gamma interferon (IFN-γ) response by natural killer (NK) cells. In fact, IFN-γ-knockout mice infected with the Chinese strain showed significantly better survival than wild-type mice. Conversely, infection with the less virulent North American strain resulted in an IFN-β-subjugated, low inflammatory response that might be beneficial for the host to clear the infection. Overall, our data suggest that a highly virulent epidemic strain has evolved to massively activate IFN-γ production, mainly by NK cells, leading to a rapid and lethal STSLS.

Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection

PubMed Central

Ko, Ya-Ping; Flick, Matthew J.

2017-01-01

Fibrinogen not only plays a pivotal role in hemostasis but also serves key roles in antimicrobial host defense. As a rapidly assembled provisional matrix protein, fibrin(ogen) can function as an early line of host protection by limiting bacterial growth, suppressing dissemination of microbes to distant sites, and mediating host bacterial killing. Fibrinogen-mediated host antimicrobial activity occurs predominantly through two general mechanisms, namely, fibrin matrices functioning as a protective barrier and fibrin(ogen) directly or indirectly driving host protective immune function. The potential of fibrin to limit bacterial infection and disease has been countered by numerous bacterial species evolving and maintaining virulence factors that engage hemostatic system components within vertebrate hosts. Bacterial factors have been isolated that simply bind fibrinogen or fibrin, promote fibrin polymer formation, or promote fibrin dissolution. Staphylococcus aureus is an opportunistic gram-positive bacterium, the causative agent of a wide range of human infectious diseases, and a prime example of a pathogen exquisitely sensitive to host fibrinogen. Indeed, current data suggest fibrinogen serves as a context-dependent determinant of host defense or pathogen virulence in Staphylococcus infection whose ultimate contribution is dictated by the expression of S. aureus virulence factors, the path of infection, and the tissue microenvironment. PMID:27056151

Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data.

PubMed Central

Drummond, Alexei J; Nicholls, Geoff K; Rodrigo, Allen G; Solomon, Wiremu

2002-01-01

Molecular sequences obtained at different sampling times from populations of rapidly evolving pathogens and from ancient subfossil and fossil sources are increasingly available with modern sequencing technology. Here, we present a Bayesian statistical inference approach to the joint estimation of mutation rate and population size that incorporates the uncertainty in the genealogy of such temporally spaced sequences by using Markov chain Monte Carlo (MCMC) integration. The Kingman coalescent model is used to describe the time structure of the ancestral tree. We recover information about the unknown true ancestral coalescent tree, population size, and the overall mutation rate from temporally spaced data, that is, from nucleotide sequences gathered at different times, from different individuals, in an evolving haploid population. We briefly discuss the methodological implications and show what can be inferred, in various practically relevant states of prior knowledge. We develop extensions for exponentially growing population size and joint estimation of substitution model parameters. We illustrate some of the important features of this approach on a genealogy of HIV-1 envelope (env) partial sequences. PMID:12136032

Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data.

PubMed

Drummond, Alexei J; Nicholls, Geoff K; Rodrigo, Allen G; Solomon, Wiremu

2002-07-01

Molecular sequences obtained at different sampling times from populations of rapidly evolving pathogens and from ancient subfossil and fossil sources are increasingly available with modern sequencing technology. Here, we present a Bayesian statistical inference approach to the joint estimation of mutation rate and population size that incorporates the uncertainty in the genealogy of such temporally spaced sequences by using Markov chain Monte Carlo (MCMC) integration. The Kingman coalescent model is used to describe the time structure of the ancestral tree. We recover information about the unknown true ancestral coalescent tree, population size, and the overall mutation rate from temporally spaced data, that is, from nucleotide sequences gathered at different times, from different individuals, in an evolving haploid population. We briefly discuss the methodological implications and show what can be inferred, in various practically relevant states of prior knowledge. We develop extensions for exponentially growing population size and joint estimation of substitution model parameters. We illustrate some of the important features of this approach on a genealogy of HIV-1 envelope (env) partial sequences.

Autophagy in the regulation of pathogen replication and adaptive immunity

PubMed Central

Randow, Felix; Münz, Christian

2012-01-01

Autophagy is an evolutionary conserved homeostatic process by which cells deliver cytoplasmic material for degradation into lysosomes. Autophagy may have evolved as a nutrient-providing homeostatic pathway induced upon starvation, but with the acquisition of cargo-receptors autophagy has become an important cellular defence mechanism as well as a generator of antigenic peptides for MHC presentation. We propose that autophagy efficiently protects against microbes encountering the cytosolic environment accidentally, for example upon phagosomal damage, while pathogens routinely accessing the host cytosol have evolved to avoid or even benefit from autophagy. PMID:22796170

Analyzing the Differences and Preferences of Pathogenic and Nonpathogenic Prokaryote Species

NASA Astrophysics Data System (ADS)

Nolen, L.; Duong, K.; Heim, N. A.; Payne, J.

2015-12-01

A limited amount of knowledge exists on the large-scale characteristics and differences of pathogenic species in comparison to all prokaryotes. Pathogenic species, like other prokaryotes, have attributes specific to their environment and lifestyles. However, because they have evolved to coexist inside their hosts, the conditions they occupy may be more limited than those of non-pathogenic species. In this study we investigate the possibility of divergent evolution between pathogenic and non-pathogenic species by examining differences that may have evolved as a result of the need to adapt to their host. For this research we analyzed data collected from over 1900 prokaryotic species and performed t-tests using R to quantify potential differences in preferences. To examine the possible divergences from nonpathogenic bacteria, we focused on three variables: cell biovolume, preferred environmental pH, and preferred environmental temperature. We also looked at differences between pathogenic and nonpathogenic species belonging to the same phylum. Our results suggest a strong divergence in abiotic preferences between the two groups, with pathogens occupying a much smaller range of temperatures and pHs than their non-pathogenic counterparts. However, while the median biovolume is different when comparing pathogens and nonpathogens, we cannot conclude that the mean values are significantly different from each other. In addition, we found evidence of convergent evolution, as the temperature and pH preferences of pathogenic bacteria species from different phlya all approach the same values. Pathogenic species do not, however, all approach the same biovolume values, suggesting that specific pH and temperature preferences are more characteristic of pathogens than certain biovolumes.

Immune evasion by pathogens of bovine respiratory disease complex.

PubMed

Srikumaran, Subramaniam; Kelling, Clayton L; Ambagala, Aruna

2007-12-01

Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

Bartonella: emerging pathogen or emerging awareness?

PubMed

Mogollon-Pasapera, Elin; Otvos, Laszlo; Giordano, Antonio; Cassone, Marco

2009-01-01

The number of known Bartonella species is rapidly growing. Some of them are responsible for distinct infectious diseases and show different prevalence and antibiotic susceptibility profiles. Not only have some vectors of Bartonella not been fully characterized, but also intermediate hosts are actually much more numerous and diverse than previously thought. Among these, dogs differ from cats because they tend to suffer an overt disease similar to humans, thus providing the base for a useful animal indicator and research model. Among the debilitating conditions with an unclear impact on the course of these infections, specific conditions (e.g., homelessness, alcoholism) have been linked to a much higher prevalence and to high risk of unfavorable outcome. Due to the limited arsenal of antibiotics effective in vivo on this peculiar intracellular pathogen, the risk/benefit balance of antibiotic therapy is sometimes difficult to draw. In this evolving picture, the recent discoveries of new species highlights the importance of basic molecular biology resources that would bring major public health benefits if available in endemic areas, and specifically in many areas of Peru and Bolivia.

Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types.

PubMed

Kubinak, Jason L; Ruff, James S; Hyzer, Cornelius Whitney; Slev, Patricia R; Potts, Wayne K

2012-02-28

The unprecedented genetic diversity found at vertebrate MHC (major histocompatibility complex) loci influences susceptibility to most infectious and autoimmune diseases. The evolutionary explanation for how these polymorphisms are maintained has been controversial. One leading explanation, antagonistic coevolution (also known as the Red Queen), postulates a never-ending molecular arms race where pathogens evolve to evade immune recognition by common MHC alleles, which in turn provides a selective advantage to hosts carrying rare MHC alleles. This cyclical process leads to negative frequency-dependent selection and promotes MHC diversity if two conditions are met: (i) pathogen adaptation must produce trade-offs that result in pathogen fitness being higher in familiar (i.e., host MHC genotype adapted to) vs. unfamiliar host MHC genotypes; and (ii) this adaptation must produce correlated patterns of virulence (i.e., disease severity). Here we test these fundamental assumptions using an experimental evolutionary approach (serial passage). We demonstrate rapid adaptation and virulence evolution of a mouse-specific retrovirus to its mammalian host across multiple MHC genotypes. Critically, this adaptive response results in trade-offs (i.e., antagonistic pleiotropy) between host MHC genotypes; both viral fitness and virulence is substantially higher in familiar versus unfamiliar MHC genotypes. These data are unique in experimentally confirming the requisite conditions of the antagonistic coevolution model of MHC evolution and providing quantification of fitness effects for pathogen and host. These data help explain the unprecedented diversity of MHC genes, including how disease-causing alleles are maintained.

Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.

PubMed

Belizário, José E; Napolitano, Mauro

2015-01-01

The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.

Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches

PubMed Central

Belizário, José E.; Napolitano, Mauro

2015-01-01

The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body’s microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies. PMID:26500616

'Drugs from bugs': bacterial effector proteins as promising biological (immune-) therapeutics.

PubMed

Rüter, Christian; Hardwidge, Philip R

2014-02-01

Immune system malfunctions cause many of the most severe human diseases. The immune system has evolved primarily to control bacterial, viral, fungal, and parasitic infections. In turn, over millions of years of coevolution, microbial pathogens have evolved various mechanisms to control and modulate the host immune system for their own benefit and survival. For example, many bacterial pathogens use virulence proteins to modulate and exploit target cell mechanisms. Our understanding of these bacterial strategies opens novel possibilities to exploit 'microbial knowledge' to control excessive immune reactions. Gaining access to strategies of microbial pathogens could lead to potentially huge benefits for the therapy of inflammatory diseases. Most work on bacterial pathogen effector proteins has the long-term aim of neutralizing the infectious capabilities of the pathogen. However, attenuated pathogens and microbial products have been used for over a century with overwhelming success in the form of vaccines to induce specific immune responses that protect against the respective infectious diseases. In this review, we focus on bacterial effector and virulence proteins capable of modulating and suppressing distinct signaling pathways with potentially desirable immune-modulating effects for treating unrelated inflammatory diseases. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

A model of directional selection applied to the evolution of drug resistance in HIV-1.

PubMed

Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

2007-04-01

Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

The evolution of immunity in relation to colonization and migration.

PubMed

O'Connor, Emily A; Cornwallis, Charlie K; Hasselquist, Dennis; Nilsson, Jan-Åke; Westerdahl, Helena

2018-05-01

Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

Genesis and Spread of Newly Emerged Highly Pathogenic H7N9 Avian Viruses in Mainland China

PubMed Central

Yang, Lei; Zhu, Wenfei; Li, Xiyan; Chen, Minmei; Wu, Jie; Yu, Pengbo; Qi, Shunxiang; Huang, Yiwei; Shi, Weixian; Dong, Jie; Zhao, Xiang; Huang, Weijuan; Li, Zi; Zeng, Xiaoxu; Bo, Hong; Chen, Tao; Chen, Wenbing; Liu, Jia; Zhang, Ye; Liang, Zhenli; Shi, Wei

2017-01-01

ABSTRACT The novel low-pathogenic avian influenza A H7N9 viruses (LPAI H7N9 viruses) have been a threat to public health since their emergence in 2013 because of the high rates of mortality and morbidity that they cause. Recently, highly pathogenic variants of these avian influenza A H7N9 viruses (HPAI H7N9 viruses) have emerged and caused human infections and outbreaks among poultry in mainland China. However, it is still unclear how the HPAI H7N9 virus was generated and how it evolved and spread in China. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze River Delta region and spread southward to the Pearl River Delta region, possibly through live poultry trade. After introduction into the Pearl River Delta region, the origin LPAI H7N9 virus acquired four amino acid insertions in the hemagglutinin (HA) protein cleavage site and mutated into the HPAI H7N9 virus in late May 2016. Afterward, the HPAI H7N9 viruses further reassorted with LPAI H7N9 or H9N2 viruses locally and generated multiple different genotypes. As of 14 July 2017, the HPAI H7N9 viruses had spread from Guangdong Province to at least 12 other provinces. The rapid geographical expansion and genetic evolution of the HPAI H7N9 viruses pose a great challenge not only to public health but also to poultry production. Effective control measures, including enhanced surveillance, are therefore urgently needed. IMPORTANCE The LPAI H7N9 virus has caused five outbreak waves in humans and was recently reported to have mutated into highly pathogenic variants. It is unknown how the HPAI H7N9 virus originated, evolved, and disseminated in China. In this study, we comprehensively analyzed the sequences of HPAI H7N9 viruses from 28 human and 21 environmental samples covering eight provinces in China that were taken from November 2016 to June 2017. The results show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze River Delta region. However, the insertion of four amino acids into the HA protein cleavage site of an LPAI H7N9 virus occurred in late May 2016 in the Pearl River Delta region. The mutated HPAI H7N9 virus further reassorted with LPAI H7N9 or H9N2 viruses that were cocirculating in poultry. Considering the rapid geographical expansion of the HPAI H7N9 viruses, effective control measures are urgently needed. PMID:28956760

Rapid methods for the detection of foodborne bacterial pathogens: principles, applications, advantages and limitations

PubMed Central

Law, Jodi Woan-Fei; Ab Mutalib, Nurul-Syakima; Chan, Kok-Gan; Lee, Learn-Han

2015-01-01

The incidence of foodborne diseases has increased over the years and resulted in major public health problem globally. Foodborne pathogens can be found in various foods and it is important to detect foodborne pathogens to provide safe food supply and to prevent foodborne diseases. The conventional methods used to detect foodborne pathogen are time consuming and laborious. Hence, a variety of methods have been developed for rapid detection of foodborne pathogens as it is required in many food analyses. Rapid detection methods can be categorized into nucleic acid-based, biosensor-based and immunological-based methods. This review emphasizes on the principles and application of recent rapid methods for the detection of foodborne bacterial pathogens. Detection methods included are simple polymerase chain reaction (PCR), multiplex PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP) and oligonucleotide DNA microarray which classified as nucleic acid-based methods; optical, electrochemical and mass-based biosensors which classified as biosensor-based methods; enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay which classified as immunological-based methods. In general, rapid detection methods are generally time-efficient, sensitive, specific and labor-saving. The developments of rapid detection methods are vital in prevention and treatment of foodborne diseases. PMID:25628612

Rapid diagnostic tests apply for pediatric infections at outpatient clinic setting.

PubMed

Ushijima, Hiroshi; Thongprachum, Aksara; Tran, Dinh Nguyen; Fujimoto, Tsuguto; Hanaoka, Nozomu; Okitsu, Shoko; Takanashi, Sayaka; Mizuguchi, Masashi; Hayakawa, Satoshi

2015-01-01

Early identification of the etiology of infection is beneficial. Most infections are treated as outpatients. However, facilities for rapid diagnosis are not available in clinic settings. We applied Immunochromatography (IC) and Loop-mediated Isothermal Amplification (LAMP) methods to rapidly diagnose pathogens among 31 children with respiratory infection and 12 with gastroenteritis at a clinic in Saitama prefecture, Japan. Pathogens were then screened by multiplex conventional and real-time PCRs and bacterial culture. Respiratory pathogens were found in 64.5%. Despite the narrow spectrum, rapid tests identified pathogens in 28.6% of cases with a high agreement rate of 89.3% with PCR. Gastroenteritis pathogens were found in 66.7%. E. coli was positive in 3 cases and all were negative for verotoxin by LAMP. The agreement rate of IC and PCR assay was high, 100%. IC and LAMP are reliable and suitable methods in limited-resource settings for early pathogenic identification, which will help appropriate management, avoid unnecessary intervention, and cost saving.

Genome sequence and rapid evolution of the rice pathogen Xanthomonas oryzae pv. oryzae PXO99A

PubMed Central

Salzberg, Steven L; Sommer, Daniel D; Schatz, Michael C; Phillippy, Adam M; Rabinowicz, Pablo D; Tsuge, Seiji; Furutani, Ayako; Ochiai, Hirokazu; Delcher, Arthur L; Kelley, David; Madupu, Ramana; Puiu, Daniela; Radune, Diana; Shumway, Martin; Trapnell, Cole; Aparna, Gudlur; Jha, Gopaljee; Pandey, Alok; Patil, Prabhu B; Ishihara, Hiromichi; Meyer, Damien F; Szurek, Boris; Verdier, Valerie; Koebnik, Ralf; Dow, J Maxwell; Ryan, Robert P; Hirata, Hisae; Tsuyumu, Shinji; Won Lee, Sang; Ronald, Pamela C; Sonti, Ramesh V; Van Sluys, Marie-Anne; Leach, Jan E; White, Frank F; Bogdanove, Adam J

2008-01-01

Background Xanthomonas oryzae pv. oryzae causes bacterial blight of rice (Oryza sativa L.), a major disease that constrains production of this staple crop in many parts of the world. We report here on the complete genome sequence of strain PXO99A and its comparison to two previously sequenced strains, KACC10331 and MAFF311018, which are highly similar to one another. Results The PXO99A genome is a single circular chromosome of 5,240,075 bp, considerably longer than the genomes of the other strains (4,941,439 bp and 4,940,217 bp, respectively), and it contains 5083 protein-coding genes, including 87 not found in KACC10331 or MAFF311018. PXO99A contains a greater number of virulence-associated transcription activator-like effector genes and has at least ten major chromosomal rearrangements relative to KACC10331 and MAFF311018. PXO99A contains numerous copies of diverse insertion sequence elements, members of which are associated with 7 out of 10 of the major rearrangements. A rapidly-evolving CRISPR (clustered regularly interspersed short palindromic repeats) region contains evidence of dozens of phage infections unique to the PXO99A lineage. PXO99A also contains a unique, near-perfect tandem repeat of 212 kilobases close to the replication terminus. Conclusion Our results provide striking evidence of genome plasticity and rapid evolution within Xanthomonas oryzae pv. oryzae. The comparisons point to sources of genomic variation and candidates for strain-specific adaptations of this pathogen that help to explain the extraordinary diversity of Xanthomonas oryzae pv. oryzae genotypes and races that have been isolated from around the world. PMID:18452608

Rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal droplets in an immuno-compromised host.

PubMed

Corchia, Anthony; Limelette, Anne; Hubault, Béatrice; Robbins, Ailsa; Quinquenel, Anne; Bani-Sadr, Firouze; N'Guyen, Yohan

2015-03-08

The rare descriptions, in the literature, of ocular infections due to Pasteurella multocida include: endophtalmitis, keratitis and corneal ulcers, Parinaud's oculoglandular syndrome, and conjunctivitis. Here, we report a rare case of rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal droplets in an immuno-compromised host. A 69-year-old, Caucasian male was referred to our department with purulent conjunctivitis, occurring five days after chemotherapy for an angioimmunoblastic-T-cell-lymphoma, and thirty-three hours after being struck in his right eye by his sneezing Dachshund dog. Physical examination revealed purulent conjunctivitis of the right eye associated with inflammatory edema of both lids. Direct bacteriological examination of conjunctival secretions showed gram-negative bacilli and regular, grey non-hemolytic colonies appearing the next day on blood agar. The oxidase test was positive for these colonies. An antibiotherapy associating intravenous amoxicillin and amoxicillin/clavulanate was administered. The outcome was favorable in the next three days allowing discharge of the patient with amoxicillin (2 g tid per os). This case report may be of interest for infectious diseases, ophthalmology or oncology specialists, especially nowadays with chemotherapy being administered in day care centres, where unusual home pathogens can be encountered in health related infections. In this case, previous animal contact and conjunctival samples showing Enterobacteriaceae like colonies with positive oxidase test were two important clues which could help clinicians to make the diagnosis of Pasteurella conjunctivitis in every day practice.

Understanding the Mechanisms of Immunopathogenesis of Human and Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

Extensive investigations have revealed that zoonotic pathogens in the Mycobacterium tuberculosis complex (MTBC) evolved from a common ancestor. Although all the members can cause disease in one or more species of mammals, Mycobacterium tuberculosis (Mtb) and M. bovis (Mbv) are the major pathogens ...

Sexually transmitted infection and the evolution of serial monogamy.

PubMed

McLeod, David V; Day, Troy

2014-12-07

The selective forces shaping mating systems have long been of interest to biologists. One particular selective pressure that has received comparatively little attention is sexually transmitted infections (STIs). While it has been hypothesized that STIs could drive the evolutionary emergence of monogamy, there is little theoretical support. Here we use an evolutionary invasion analysis to determine what aspects of pathogen virulence and transmission are necessary for serial monogamy to evolve in a promiscuous population. We derive a biologically intuitive invasion condition in terms of population-specific quantities. From this condition, we obtain two main results. First, when pathogen virulence causes mortality rather than sterility, monogamy is more likely to evolve. Second, we find that at intermediate pathogen transmission rates, monogamy is the most selectively advantageous, whereas at high- and low-transmission rates, monogamy is generally selected against. As a result, it is possible for a pathogen to be highly virulent, yet for promiscuity to persist. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Genomic Potential of Stenotrophomonas maltophilia in Bioremediation with an Assessment of Its Multifaceted Role in Our Environment

PubMed Central

Mukherjee, Piyali; Roy, Pranab

2016-01-01

The gram negative bacterium Stenotrophomonas is rapidly evolving as a nosocomial pathogen in immuno-compromised patients. Treatment of Stenotrophomonas maltophilia infections is problematic because of their increasing resistance to multiple antibiotics. This article aims to review the multi-disciplinary role of Stenotrophomonas in our environment with special focus on their metabolic and genetic potential in relation to bioremediation and phytoremediation. Current and emerging treatments and diagnosis for patients infected with S. maltophilia are discussed besides their capability of production of novel bioactive compounds. The plant growth promoting characteristics of this bacterium has been considered with special reference to secondary metabolite production. Nano-particle synthesis by Stenotrophomonas has also been reviewed in addition to their applications as effective biocontrol agents in plant and animal pathogenesis. PMID:27446008

The glycoprotein TRP36 of Ehrlichia sp. UFMG-EV and related cattle pathogen Ehrlichia sp. UFMT-BV evolved from a highly variable clade of E. canis under adaptive diversifying selection.

PubMed

Cabezas-Cruz, Alejandro; Valdés, James J; de la Fuente, José

2014-12-10

A new species of Ehrlichia, phylogenetically distant from E. ruminantium, was found in 2010 infecting cattle in Canada. In 2012 and 2013, we reported the in vitro propagation, molecular and ultrastructural characterization of Ehrlichia sp. UFMG-EV (E. mineirensis), a new species of Ehrlichia isolated from the haemolymph of Brazilian Rhipicephalus (Boophilus) microplus ticks. A new organism, named Ehrlichia sp. UFMT-BV, closely related to Ehrlichia sp. UFMG-EV, was recently described in Brazil and after experimental infection it was shown to be pathogenic for cattle. This new emerging clade of cattle Ehrlichia pathogens is closely related to E. canis. The major immunogenic Tandem Repeat Protein (TRP36; also known as gp36) is extensively used to characterize the genetic diversity of E. canis. Homologs of TRP36 were found in both Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV. Herein, we characterized the evolution of this new Ehrlichia clade using TRP36 sequences. Our working hypothesis is that Ehrlichia sp. UFMG-EV and related microorganisms evolved from a highly variable E. canis clade. In support of our hypothesis we found that Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV TRP36 evolved from a highly divergent and variable clade within E. canis and this clade evolved under episodic diversifying selection with a high proportion of sites under positive selection. Our results suggest that Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV evolved from a variable clade within E. canis.

Rapid quantification of soilborne pathogen communities in wheat-based long-term field experiments

USDA-ARS?s Scientific Manuscript database

Traditional isolation and quantification of inoculum density is difficult for most soilborne pathogens. Quantitative PCR methods have been developed to rapidly identify and quantify many of these pathogens using a single DNA extract from soil. Rainfed experiments operated continuously for up to 84 y...

Fine-Scale Recombination Maps of Fungal Plant Pathogens Reveal Dynamic Recombination Landscapes and Intragenic Hotspots

PubMed Central

Stukenbrock, Eva H.; Dutheil, Julien Y.

2018-01-01

Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation, and rates of adaptation. In many organisms, recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogen Zymoseptoria tritici and a sister species infecting wild grasses Z. ardabiliae. We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres, and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots colocalize between the two species, suggesting that hotspot dynamics contribute to the overall pattern of fast evolving recombination in these species. PMID:29263029

Fine-Scale Recombination Maps of Fungal Plant Pathogens Reveal Dynamic Recombination Landscapes and Intragenic Hotspots.

PubMed

Stukenbrock, Eva H; Dutheil, Julien Y

2018-03-01

Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation, and rates of adaptation. In many organisms, recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate and positions of recombination hotspot can be studied using population genomics data and statistical methods. In this study, we conducted population genomics analyses to address the evolution of recombination in two closely related fungal plant pathogens: the prominent wheat pathogen Zymoseptoria tritici and a sister species infecting wild grasses Z. ardabiliae We specifically addressed whether recombination landscapes, including hotspot positions, are conserved in the two recently diverged species and if recombination contributes to rapid evolution of pathogenicity traits. We conducted a detailed simulation analysis to assess the performance of methods of recombination rate estimation based on patterns of linkage disequilibrium, in particular in the context of high nucleotide diversity. Our analyses reveal overall high recombination rates, a lack of suppressed recombination in centromeres, and significantly lower recombination rates on chromosomes that are known to be accessory. The comparison of the recombination landscapes of the two species reveals a strong correlation of recombination rate at the megabase scale, but little correlation at smaller scales. The recombination landscapes in both pathogen species are dominated by frequent recombination hotspots across the genome including coding regions, suggesting a strong impact of recombination on gene evolution. A significant but small fraction of these hotspots colocalize between the two species, suggesting that hotspot dynamics contribute to the overall pattern of fast evolving recombination in these species. Copyright © 2018 Stukenbrock and Dutheil.

The Evolution of Foodborne Pathogens

NASA Astrophysics Data System (ADS)

Abu-Ali, Galeb S.; Manning, Shannon D.

Despite continuous advances in food safety and disease surveillance, control, and prevention, foodborne bacterial infections remain a major public health concern. Because foodborne pathogens are commonly exposed to multiple environmental stressors, such as low pH and antibiotics, most have evolved specific mechanisms to facilitate survival in adverse environments.

Host target modification as a strategy to counter pathogen hijacking of the jasmonate hormone receptor

DOE PAGES

Zhang, Li; Yao, Jian; Withers, John; ...

2015-11-02

In the past decade, characterization of the host targets of pathogen virulence factors took a center stage in the study of pathogenesis and disease susceptibility in plants and humans. However, the impressive knowledge of host targets has not been broadly exploited to inhibit pathogen infection. In this paper, we show that host target modification could be a promising new approach to “protect” the disease-vulnerable components of plants. In particular, recent studies have identified the plant hormone jasmonate (JA) receptor as one of the common targets of virulence factors from highly evolved biotrophic/hemibiotrophic pathogens. Strains of the bacterial pathogen Pseudomonas syringae,more » for example, produce proteinaceous effectors, as well as a JA-mimicking toxin, coronatine (COR), to activate JA signaling as a mechanism to promote disease susceptibility. Guided by the crystal structure of the JA receptor and evolutionary clues, we succeeded in modifying the JA receptor to allow for sufficient endogenous JA signaling but greatly reduced sensitivity to COR. Transgenic Arabidopsis expressing this modified receptor not only are fertile and maintain a high level of insect defense, but also gain the ability to resist COR-producing pathogens Pseudomonas syringae pv. tomato and P. syringae pv. maculicola. Finally, our results provide a proof-of-concept demonstration that host target modification can be a promising new approach to prevent the virulence action of highly evolved pathogens.« less

PCPPI: a comprehensive database for the prediction of Penicillium-crop protein-protein interactions

USDA-ARS?s Scientific Manuscript database

Penicillium expansum, the causal agent of blue mold, is one of the most prevalent postharvest pathogens infecting a wide range of crops after harvest. In response, crops have evolved various defense systems to protect themselves against this and other pathogens. Penicillium-crop interaction is a m...

Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen

USDA-ARS?s Scientific Manuscript database

Disease resistance (R) genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLRs define the fastest evolving...

Adaptive evolution has targeted the C-terminal domain of the RXLR effectors of plant pathogenic oomycetes.

PubMed

Win, Joe; Kamoun, Sophien

2008-04-01

Plant pathogenic microbes deliver effector proteins inside host cells to modulate plant defense circuitry and enable parasitic colonization. As genome sequences from plant pathogens become available, genome-wide evolutionary analyses will shed light on how pathogen effector genes evolved and adapted to the cellular environment of their host plants. In the August 2007 issue of Plant Cell, we described adaptive evolution (positive selection) in the cytoplasmic RXLR effectors of three recently sequenced oomycete plant pathogens. Here, we summarize our findings and describe additional data that further validate our approach.

Commercial strain-derived clinical Saccharomyces cerevisiae can evolve new phenotypes without higher pathogenicity.

PubMed

Pfliegler, Walter P; Boros, Enikő; Pázmándi, Kitti; Jakab, Ágnes; Zsuga, Imre; Kovács, Renátó; Urbán, Edit; Antunovics, Zsuzsa; Bácsi, Attila; Sipiczki, Matthias; Majoros, László; Pócsi, István

2017-11-01

Saccharomyces cerevisiae is one of the most important microbes in food industry, but there is growing evidence on its potential pathogenicity as well. Its status as a member of human mycobiome is still not fully understood. In this study, we characterize clinical S. cerevisiae isolates from Hungarian hospitals along with commercial baking and probiotic strains, and determine their phenotypic parameters, virulence factors, interactions with human macrophages, and pathogenicity. Four of the clinical isolates could be traced back to commercial strains based on genetic fingerprinting. Our observations indicate that the commercial-derived clinical isolates have evolved new phenotypes and show similar, or in two cases, significantly decreased pathogenicity. Furthermore, immunological experiments revealed that the variability in human primary macrophage activation after coincubation with yeasts is largely donor and not isolate dependent. Isolates in this study offer an interesting insight into the potential microevolution of probiotic and food strains in human hosts. These commensal yeasts display various changes in their phenotypes, indicating that the colonization of the host does not necessarily impose a selective pressure toward higher virulence/pathogenicity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid Identification of Pathogens from Positive Blood Cultures by Multiplex PCR using the FilmArray System

PubMed Central

Blaschke, Anne J.; Heyrend, Caroline; Byington, Carrie L.; Fisher, Mark A.; Barker, Elizabeth; Garrone, Nicholas F.; Thatcher, Stephanie A.; Pavia, Andrew T.; Barney, Trenda; Alger, Garrison D.; Daly, Judy A.; Ririe, Kirk M.; Ota, Irene; Poritz, Mark A.

2012-01-01

Sepsis is a leading cause of death. Rapid and accurate identification of pathogens and antimicrobial resistance directly from blood culture could improve patient outcomes. The FilmArray® (FA; Idaho Technology, Inc., Salt Lake City, UT) Blood Culture (BC) panel can identify > 25 pathogens and 4 antibiotic resistance genes from positive blood cultures in 1 hour. We compared a development version of the panel to conventional culture and susceptibility testing on 102 archived blood cultures from adults and children with bacteremia. Of 109 pathogens identified by culture, 95% were identified by FA. Among 111 prospectively collected blood cultures, the FA identified 84 of 92 pathogens (91%) covered by the panel. Among 25 Staphylococcus aureus and 21 Enterococcus species detected, FA identified all culture-proven MRSA and VRE. The FA BC panel is an accurate method for the rapid identification of pathogens and resistance genes from blood culture. PMID:22999332

Predation on multiple trophic levels shapes the evolution of pathogen virulence.

PubMed

Friman, Ville-Petri; Lindstedt, Carita; Hiltunen, Teppo; Laakso, Jouni; Mappes, Johanna

2009-08-25

The pathogen virulence is traditionally thought to co-evolve as a result of reciprocal selection with its host organism. In natural communities, pathogens and hosts are typically embedded within a web of interactions with other species, which could affect indirectly the pathogen virulence and host immunity through trade-offs. Here we show that selection by predation can affect both pathogen virulence and host immune defence. Exposing opportunistic bacterial pathogen Serratia marcescens to predation by protozoan Tetrahymena thermophila decreased its virulence when measured as host moth Parasemia plantaginis survival. This was probably because the bacterial anti-predatory traits were traded off with bacterial virulence factors, such as motility or resource use efficiency. However, the host survival depended also on its allocation to warning signal that is used against avian predation. When infected with most virulent ancestral bacterial strain, host larvae with a small warning signal survived better than those with an effective large signal. This suggests that larval immune defence could be traded off with effective defence against bird predators. However, the signal size had no effect on larval survival when less virulent control or evolved strains were used for infection suggesting that anti-predatory defence against avian predators, might be less constrained when the invading pathogen is rather low in virulence. Our results demonstrate that predation can be important indirect driver of the evolution of both pathogen virulence and host immunity in communities with multiple species interactions. Thus, the pathogen virulence should be viewed as a result of both past evolutionary history, and current ecological interactions.

Early emergence of Yersinia pestis as a severe respiratory pathogen

PubMed Central

Zimbler, Daniel L.; Schroeder, Jay A.; Eddy, Justin L.; Lathem, Wyndham W.

2015-01-01

Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals. PMID:26123398

Early emergence of Yersinia pestis as a severe respiratory pathogen.

PubMed

Zimbler, Daniel L; Schroeder, Jay A; Eddy, Justin L; Lathem, Wyndham W

2015-06-30

Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA.

PubMed

Drummond, A; Rodrigo, A G

2000-12-01

Reconstruction of evolutionary relationships from noncontemporaneous molecular samples provides a new challenge for phylogenetic reconstruction methods. With recent biotechnological advances there has been an increase in molecular sequencing throughput, and the potential to obtain serial samples of sequences from populations, including rapidly evolving pathogens, is fast being realized. A new method called the serial-sample unweighted pair grouping method with arithmetic means (sUPGMA) is presented that reconstructs a genealogy or phylogeny of sequences sampled serially in time using a matrix of pairwise distances. The resulting tree depicts the terminal lineages of each sample ending at a different level consistent with the sample's temporal order. Since sUPGMA is a variant of UPGMA, it will perform best when sequences have evolved at a constant rate (i.e., according to a molecular clock). On simulated data, this new method performs better than standard cluster analysis under a variety of longitudinal sampling strategies. Serial-sample UPGMA is particularly useful for analysis of longitudinal samples of viruses and bacteria, as well as ancient DNA samples, with the minimal requirement that samples of sequences be ordered in time.

Advances in the understanding of cancer immunotherapy.

PubMed

Shore, Neal D

2015-09-01

The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies. © 2014 The Authors. BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Within-host co-evolution of chronic viruses and the adaptive immune system

NASA Astrophysics Data System (ADS)

Nourmohammad, Armita

We normally think of evolution occurring in a population of organisms, in response to their external environment. Rapid evolution of cellular populations also occurs within our bodies, as the adaptive immune system works to eliminate infection. Some pathogens, such as HIV, are able to persist in a host for extended periods of time, during which they also evolve to evade the immune response. In this talk I will introduce an analytical framework for the rapid co-evolution of B-cell and viral populations, based on the molecular interactions between them. Since the co-evolution of antibodies and viruses is perpetually out of equilibrium, I will show how to quantify the amount of adaptation in each of the two populations by analysis of their co-evolutionary history. I will discuss the consequences of competition between lineages of antibodies, and characterize the fate of a given lineage dependent on the state of the antibody and viral populations. In particular, I will discuss the conditions for emergence of highly potent broadly neutralizing antibodies, which are now recognized as critical for designing an effective vaccine against HIV.

Cell Surface and Membrane Engineering: Emerging Technologies and Applications

PubMed Central

Saeui, Christopher T.; Mathew, Mohit P.; Liu, Lingshui; Urias, Esteban; Yarema, Kevin J.

2015-01-01

Membranes constitute the interface between the basic unit of life—a single cell—and the outside environment and thus in many ways comprise the ultimate “functional biomaterial”. To perform the many and often conflicting functions required in this role, for example to partition intracellular contents from the outside environment while maintaining rapid intake of nutrients and efflux of waste products, biological membranes have evolved tremendous complexity and versatility. This article describes how membranes, mainly in the context of living cells, are increasingly being manipulated for practical purposes with drug discovery, biofuels, and biosensors providing specific, illustrative examples. Attention is also given to biology-inspired, but completely synthetic, membrane-based technologies that are being enabled by emerging methods such as bio-3D printers. The diverse set of applications covered in this article are intended to illustrate how these versatile technologies—as they rapidly mature—hold tremendous promise to benefit human health in numerous ways ranging from the development of new medicines to sensitive and cost-effective environmental monitoring for pathogens and pollutants to replacing hydrocarbon-based fossil fuels. PMID:26096148

Biocontrol and Rapid Detection of Food-Borne Pathogens Using Bacteriophages and Endolysins

PubMed Central

Bai, Jaewoo; Kim, You-Tae; Ryu, Sangryeol; Lee, Ju-Hoon

2016-01-01

Bacteriophages have been suggested as natural food preservatives as well as rapid detection materials for food-borne pathogens in various foods. Since Listeria monocytogenes-targeting phage cocktail (ListShield) was approved for applications in foods, numerous phages have been screened and experimentally characterized for phage applications in foods. A single phage and phage cocktail treatments to various foods contaminated with food-borne pathogens including E. coli O157:H7, Salmonella enterica, Campylobacter jejuni, Listeria monocytogenes, Staphylococcus aureus, Cronobacter sakazakii, and Vibrio spp. revealed that they have great potential to control various food-borne pathogens and may be alternative for conventional food preservatives. In addition, phage-derived endolysins with high host specificity and host lysis activities may be preferred to food applications rather than phages. For rapid detection of food-borne pathogens, cell-wall binding domains (CBDs) from endolysins have been suggested due to their high host-specific binding. Fluorescence-tagged CBDs have been successfully evaluated and suggested to be alternative materials of expensive antibodies for various detection applications. Most recently, reporter phage systems have been developed and tested to confirm their usability and accuracy for specific detection. These systems revealed some advantages like rapid detection of only viable pathogenic cells without interference by food components in a very short reaction time, suggesting that these systems may be suitable for monitoring of pathogens in foods. Consequently, phage is the next-generation biocontrol agent as well as rapid detection tool to confirm and even identify the food-borne pathogens present in various foods. PMID:27092128

Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

USDA-ARS?s Scientific Manuscript database

Novel subtypes of Eurasian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4 such as H5N2, H5N5, H5N6, and H5N8 have been identified in China since 2008 and subsequently evolved into four genetically distinct groups (A – D) of clade 2.3.4.4...

The importance of multilocus sequence typing: cautionary tales from the bacterium Xylella fastidiosa.

PubMed

Nunney, L; Elfekih, S; Stouthamer, R

2012-05-01

Microbial identification methods have evolved rapidly over the last few decades. One such method is multilocus sequence typing (MLST). MLST is a powerful tool for understanding the evolutionary dynamics of pathogens and to gain insight into their genetic diversity. We illustrate the importance of accurate typing by reporting on three problems that have arisen in the study of a single bacterial species, the plant pathogen Xylella fastidiosa. Two of these were particularly serious since they concerned contamination of important research material that has had detrimental consequences for Xylella research: the contamination of DNA used in the sequencing of an X. fastidiosa genome (Ann-1) with DNA from another X. fastidiosa strain, and the unrecognized mislabeling of a strain (Temecula1) distributed from a culture collection (ATCC). We advocate the routine use of MLST to define strains maintained in culture collections and emphasize the importance of confirming the purity of DNA submitted for sequencing. We also present a third example that illustrates the value of MLST in guiding the choice of taxonomic types. Beyond these situations, there is a strong case for MLST whenever an isolate is used experimentally, especially where genotypic differences are suspected to influence the outcome.

The impact of rapid evolution on population dynamics in the wild: experimental test of eco-evolutionary dynamics.

PubMed

Turcotte, Martin M; Reznick, David N; Hare, J Daniel

2011-11-01

Rapid evolution challenges the assumption that evolution is too slow to impact short-term ecological dynamics. This insight motivates the study of 'Eco-Evolutionary Dynamics' or how evolution and ecological processes reciprocally interact on short time scales. We tested how rapid evolution impacts concurrent population dynamics using an aphid (Myzus persicae) and an undomesticated host (Hirschfeldia incana) in replicated wild populations. We manipulated evolvability by creating non-evolving (single clone) and potentially evolving (two-clone) aphid populations that contained genetic variation in intrinsic growth rate. We observed significant evolution in two-clone populations whether or not they were exposed to predators and competitors. Evolving populations grew up to 42% faster and attained up to 67% higher density, compared with non-evolving control populations but only in treatments exposed to competitors and predators. Increased density also correlates with relative fitness of competing clones suggesting a full eco-evolutionary dynamic cycle defined as reciprocal interactions between evolution and density. © 2011 Blackwell Publishing Ltd/CNRS.

Antibiotic Resistance in Plant-Pathogenic Bacteria.

PubMed

Sundin, George W; Wang, Nian

2018-06-01

Antibiotics have been used for the management of relatively few bacterial plant diseases and are largely restricted to high-value fruit crops because of the expense involved. Antibiotic resistance in plant-pathogenic bacteria has become a problem in pathosystems where these antibiotics have been used for many years. Where the genetic basis for resistance has been examined, antibiotic resistance in plant pathogens has most often evolved through the acquisition of a resistance determinant via horizontal gene transfer. For example, the strAB streptomycin-resistance genes occur in Erwinia amylovora, Pseudomonas syringae, and Xanthomonas campestris, and these genes have presumably been acquired from nonpathogenic epiphytic bacteria colocated on plant hosts under antibiotic selection. We currently lack knowledge of the effect of the microbiome of commensal organisms on the potential of plant pathogens to evolve antibiotic resistance. Such knowledge is critical to the development of robust resistance management strategies to ensure the safe and effective continued use of antibiotics in the management of critically important diseases. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Phylogenetic lineages in the Capnodiales

PubMed Central

Crous, P.W.; Schoch, C.L.; Hyde, K.D.; Wood, A.R.; Gueidan, C.; de Hoog, G.S.; Groenewald, J.Z.

2009-01-01

The Capnodiales incorporates plant and human pathogens, endophytes, saprobes and epiphytes, with a wide range of nutritional modes. Several species are lichenised, or occur as parasites on fungi, or animals. The aim of the present study was to use DNA sequence data of the nuclear ribosomal small and large subunit RNA genes to test the monophyly of the Capnodiales, and resolve families within the order. We designed primers to allow the amplification and sequencing of almost the complete nuclear ribosomal small and large subunit RNA genes. Other than the Capnodiaceae (sooty moulds), and the Davidiellaceae, which contains saprobes and plant pathogens, the order presently incorporates families of major plant pathological importance such as the Mycosphaerellaceae, Teratosphaeriaceae and Schizothyriaceae. The Piedraiaceae was not supported, but resolves in the Teratosphaeriaceae. The Dissoconiaceae is introduced as a new family to accommodate Dissoconium and Ramichloridium. Lichenisation, as well as the ability to be saprobic or plant pathogenic evolved more than once in several families, though the taxa in the upper clades of the tree lead us to conclude that the strictly plant pathogenic, nectrotrophic families evolved from saprobic ancestors (Capnodiaceae), which is the more primitive state. PMID:20169022

A newly evolved Drosophila Cytorace-9 shows trade-off between longevity and immune response.

PubMed

Sinam, Yoirentomba Meetei; Chatterjee, Arunita; Ranjini, Mysore S; Poojari, Adarsh; Nagarajan, Aarthi; Ramachandra, Nallur B; Nongthomba, Upendra

2016-10-01

Species with an efficient immune system would be at an advantage to evade pathogenic challenges and adapt to an ever changing ecological niche. The upkeep of immunity is a costly affair, thus trade-offs between immunity and other life history traits are expected. However, studies on the relation between immunity and life span have yielded paradoxical results. Drosophila Cytoraces, being at different stages of evolutionary divergence, provide an excellent experimental model system to study how evolving populations gain novel traits in the absence of selection. We found that in the absence of pathogenic infections, the Cytorace-9 flies lived longer than those of Cytorace-3. However, when these Cytoraces were challenged with different pathogenic microbes, the trend was opposite. After infection with pathogens, the long-lived Cytorace-9 survived worse than the short lived Cytorace-3, which can be attributed to a reduction in its immune response. This study provides evidence to support the existence of a trade-off between life span and immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification and utilization of a sow thistle powdery mildew as a poorly adapted pathogen to dissect post-invasion non-host resistance mechanisms in Arabidopsis

PubMed Central

Wen, Yingqiang; Wang, Wenming; Feng, Jiayue; Luo, Ming-Cheng; Tsuda, Kenichi; Katagiri, Fumiaki; Bauchan, Gary; Xiao, Shunyuan

2011-01-01

To better dissect non-host resistance against haustorium-forming powdery mildew pathogens, a sow thistle powdery mildew isolate designated Golovinomyces cichoracearum UMSG1 that has largely overcome penetration resistance but is invariably stopped by post-invasion non-host resistance of Arabidopsis thaliana was identified. The post-invasion non-host resistance is mainly manifested as the formation of a callosic encasement of the haustorial complex (EHC) and hypersensitive response (HR), which appears to be controlled by both salicylic acid (SA)-dependent and SA-independent defence pathways, as supported by the susceptibility of the pad4/sid2 double mutant to the pathogen. While the broad-spectrum resistance protein RPW8.2 enhances post-penetration resistance against G. cichoracearum UCSC1, a well-adapted powdery mildew pathogen, RPW8.2, is dispensable for post-penetration resistance against G. cichoracearum UMSG1, and its specific targeting to the extrahaustorial membrane is physically blocked by the EHC, resulting in HR cell death. Taken together, the present work suggests an evolutionary scenario for the Arabidopsis–powdery mildew interaction: EHC formation is a conserved subcellular defence evolved in plants against haustorial invasion; well-adapted powdery mildew has evolved the ability to suppress EHC formation for parasitic growth and reproduction; RPW8.2 has evolved to enhance EHC formation, thereby conferring haustorium-targeted, broad-spectrum resistance at the post-invasion stage. PMID:21193574

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

PubMed Central

Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Evolutionary dynamics of avian influenza A H7N9 virus across five waves in mainland China, 2013-2017.

PubMed

Xiang, Dan; Pu, Zhiqing; Luo, Tingting; Guo, Fucheng; Li, Xiaobing; Shen, Xuejuan; Irwin, David M; Murphy, Robert W; Liao, Ming; Shen, Yongyi

2018-05-25

Since its emergence in March 2013, novel avian influenza A H7N9 virus has triggered five epidemics of human infections in China. This raises concerns about the pandemic threat of this quickly evolving H7N9 subtype for humans. In this study, we evaluated all available genomes for H7N9 and H9N2 influenza A viruses. Our assessment discovered that H7N9 of the 1st wave had the lowest nucleotide diversity, which then experienced substantial and rapid population expansion from a small founder population. From the 2nd wave, their nucleotide diversity increased quickly, indicating that H7N9 viruses had acquired larger populations and mutations after their initial emergence in 2013. After the phylogeographic divergence in the 2nd wave, although the HA and NA genes from different regions differed, compared to previous epidemics, the evolving H7N9 viruses in the 5th wave lost most of their previous clades. The highly pathogenic avian influenza (HPAI) H7N9 viruses in the 5th wave clustered together, and clustered close to the low pathogenic avian influenza (LPAI) virus isolated from the Pearl River Delta in the 3rd and 4th waves. This result supports the origin of HPAI H7N9 viruses was in the Pearl River Delta. In the 5th wave, although both HPAI and LPAI H7N9 viruses were isolated from the Pearl River Delta, their HA and NA genes were phylogenetically distinct. Copyright © 2018. Published by Elsevier Ltd.

Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus.

PubMed

Monaco, Monica; Pimentel de Araujo, Fernanda; Cruciani, Melania; Coccia, Eliana M; Pantosti, Annalisa

2017-01-01

Staphylococcus aureus is an important human pathogen, responsible for infections in the community and the healthcare setting. Although much of the attention is focused on the methicillin-resistant "variant" MRSA, the methicillin-susceptible counterpart (MSSA) remains a prime species in infections. The epidemiology of S. aureus, especially of MRSA, showed a rapid evolution in the last years. After representing a typical nosocomial multidrug-resistant pathogen, MRSA has recently emerged in the community and among farmed animals thanks to its ability to evolve and adapt to different settings. Global surveillance has shown that MRSA represents a problem in all continents and countries where studies have been carried out, determining an increase in mortality and the need to use last-resource expensive antibiotics. S. aureus can easily acquire resistance to antibiotics and MRSA is characteristically multidrug resistant. Resistance to vancomycin, the principal anti-MRSA antibiotic is rare, although isolates with decreased susceptibility are recovered in many areas. Resistance to the more recently introduced antibiotics, linezolid and daptomycin, has emerged; however, they remain substantially active against the large majority of MSSA and MRSA. Newer antistaphylococcal drugs have been developed, but since their clinical use has been very limited so far, little is known about the emergence of resistance. Molecular typing techniques have allowed to identify the major successful clones and lineages of MSSA and MRSA, including high-risk clones, and to trace their diffusion. In the face of a continuously evolving scenario, this review depicts the most common clones circulating in different geographical areas and in different settings at present. Since the evolution of S. aureus will continue, it is important to maintain the attention on the epidemiology of S. aureus in the future with a global view.

Genome sequence of E. coli O104:H4 leads to rapid development of a targeted antimicrobial agent against this emerging pathogen.

USDA-ARS?s Scientific Manuscript database

A recent widespread outbreak of Escherichia coli O104:H4 in Germany demonstrates the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. Rapid genomic sequencing and public availability of these data from the German outbreak strain allo...

Detection of Biomarkers of Pathogenic Naegleria fowleri Through Mass Spectrometry and Proteomics

PubMed Central

Moura, Hercules; Izquierdo, Fernando; Woolfitt, Adrian R.; Wagner, Glauber; Pinto, Tatiana; del Aguila, Carmen; Barr, John R.

2017-01-01

Emerging methods based on mass spectrometry (MS) can be used in the rapid identification of microorganisms. Thus far, these practical and rapidly evolving methods have mainly been applied to characterize prokaryotes. We applied matrix-assisted laser-desorption-ionization-time-of-flight mass spectrometry MALDI-TOF MS in the analysis of whole cells of 18 N. fowleri isolates belonging to three genotypes. Fourteen originated from the cerebrospinal fluid or brain tissue of primary amoebic meningoencephalitis patients and four originated from water samples of hot springs, rivers, lakes or municipal water supplies. Whole Naegleria trophozoites grown in axenic cultures were washed and mixed with MALDI matrix. Mass spectra were acquired with a 4700 TOF-TOF instrument. MALDI-TOF MS yielded consistent patterns for all isolates examined. Using a combination of novel data processing methods for visual peak comparison, statistical analysis and proteomics database searching we were able to detect several biomarkers that can differentiate all species and isolates studied, along with common biomarkers for all N. fowleri isolates. Naegleria fowleri could be easily separated from other species within the genus Naegleria. A number of peaks detected were tentatively identified. MALDI-TOF MS fingerprinting is a rapid, reproducible, high-throughput alternative method for identifying Naegleria isolates. This method has potential for studying eukaryotic agents. PMID:25231600

Identification, characterisation and expression analysis of natural killer receptor genes in Chlamydia pecorum infected koalas (Phascolarctos cinereus).

PubMed

Morris, Katrina M; Mathew, Marina; Waugh, Courtney; Ujvari, Beata; Timms, Peter; Polkinghorne, Adam; Belov, Katherine

2015-10-15

Koalas (Phascolarctos cinereus), an iconic Australian marsupial, are being heavily impacted by the spread of Chlamydia pecorum, an obligate intracellular bacterial pathogen. Koalas vary in their response to this pathogen, with some showing no symptoms, while others suffer severe symptoms leading to infertility, blindness or death. Little is known about the pathology of this disease and the immune response against it in this host. Studies have demonstrated that natural killer (NK) cells, key components of the innate immune system, are involved in the immune response to chlamydial infections in humans. These cells can directly lyse cells infected by intracellular pathogens and their ability to recognise these infected cells is mediated through NK receptors on their surface. These are encoded in two regions of the genome, the leukocyte receptor complex (LRC) and the natural killer complex (NKC). These two families evolve rapidly and different repertoires of genes, which have evolved by gene duplication, are seen in different species. In this study we aimed to characterise genes belonging to the NK receptor clusters in the koala by searching available koala transcriptomes using a combination of search methods. We developed a qPCR assay to quantify relative expression of four genes, two encoded within the NK receptor cluster (CLEC1B, CLEC4E) and two known to play a role in NK response to Chalmydia in humans (NCR3, PRF1). We found that the NK receptor repertoire of the koala closely resembles that of the Tasmanian devil, with minimal genes in the NKC, but with lineage specific expansions in the LRC. Additional genes important for NK cell activity, NCR3 and PRF1, were also identified and characterised. In a preliminary study to investigate whether these genes are involved in the koala immune response to infection by its chlamydial pathogen, C. pecorum, we investigated the expression of four genes in koalas with active chlamydia infection, those with past infection and those without infection using qPCR. This analysis revealed that one of these four, CLEC4E, may be upregulated in response to chlamydia infection. We have characterised genes of the NKC and LRC in koalas and have discovered evidence that one of these genes may be upregulated in koalas with chlamydia, suggesting that these receptors may play a role in the immune response of koalas to chlamydia infection.

An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor

PubMed Central

Dagdas, Yasin F; Belhaj, Khaoula; Maqbool, Abbas; Chaparro-Garcia, Angela; Pandey, Pooja; Petre, Benjamin; Tabassum, Nadra; Cruz-Mireles, Neftaly; Hughes, Richard K; Sklenar, Jan; Win, Joe; Menke, Frank; Findlay, Kim; Banfield, Mark J; Kamoun, Sophien; Bozkurt, Tolga O

2016-01-01

Plants use autophagy to safeguard against infectious diseases. However, how plant pathogens interfere with autophagy-related processes is unknown. Here, we show that PexRD54, an effector from the Irish potato famine pathogen Phytophthora infestans, binds host autophagy protein ATG8CL to stimulate autophagosome formation. PexRD54 depletes the autophagy cargo receptor Joka2 out of ATG8CL complexes and interferes with Joka2's positive effect on pathogen defense. Thus, a plant pathogen effector has evolved to antagonize a host autophagy cargo receptor to counteract host defenses. DOI: http://dx.doi.org/10.7554/eLife.10856.001 PMID:26765567

Multiplexed lateral flow microarray assay for detection of citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis pv citri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cary,; Bruce, R; Stubben, Christopher J

The invention provides highly sensitive and specific assays for the major citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis, including a field deployable multiplexed assay capable of rapidly assaying for both pathogens simultaneously. The assays are directed at particular gene targets derived from pathogenic strains that specifically cause the major citrus diseases of citrus variegated chlorosis (Xylella fastidiosa 9a5c) and citrus canker (Xanthomonas axonopodis pv citri). The citrus pathogen assays of the invention offer femtomole sensitivity, excellent linear dynamic range, and rapid and specific detection.

Rapid Screening of Natural Plant Extracts with Calcium Diacetate for Differential Effects Against Foodborne Pathogens and a Probiotic Bacterium.

PubMed

Colonna, William; Brehm-Stecher, Byron; Shetty, Kalidas; Pometto, Anthony

2017-12-01

This study focused on advancing a rapid turbidimetric bioassay to screen antimicrobials using specific cocktails of targeted foodborne bacterial pathogens. Specifically, to show the relevance of this rapid screening tool, the antimicrobial potential of generally recognized as safe calcium diacetate (DAX) and blends with cranberry (NC) and oregano (OX) natural extracts was evaluated. Furthermore, the same extracts were evaluated against beneficial lactic acid bacteria. The targeted foodborne pathogens evaluated were Escherichia coli O157:H7, Salmonella spp., Listeria monocytogenes, and Staphylococcus aureus using optimized initial cocktails (∼10 8 colony-forming unit/mL) containing strains isolated from human food outbreaks. Of all extracts evaluated, 0.51% (w/v) DAX in ethanol was the most effective against all four pathogens. However, DAX when reduced to 0.26% and with added blends from ethanol extractions consisting of DAX:OX (3:1), slightly outperformed or was equal to same levels of DAX alone. Subculture of wells in which no growth occurred after 1 week indicated that all water and ethanol extracts were bacteriostatic against the pathogens tested. All the targeted antimicrobials had no effect on the probiotic organism Lactobacillus plantarum. The use of such rapid screening methods combined with the use of multistrain cocktails of targeted foodborne pathogens from outbreaks will allow rapid large-scale screening of antimicrobials and enable further detailed studies in targeted model food systems.

Rapid multiplex detection of 10 foodborne pathogens with an up-converting phosphor technology-based 10-channel lateral flow assay

PubMed Central

Zhao, Yong; Wang, Haoran; Zhang, Pingping; Sun, Chongyun; Wang, Xiaochen; Wang, Xinrui; Yang, Ruifu; Wang, Chengbin; Zhou, Lei

2016-01-01

The rapid high-throughput detection of foodborne pathogens is essential in controlling food safety. In this study, a 10-channel up-converting phosphor technology-based lateral flow (TC-UPT-LF) assay was established for the rapid and simultaneous detection of 10 epidemic foodborne pathogens. Ten different single-target UPT-LF strips were developed and integrated into one TC-UPT-LF disc with optimization. Without enrichment the TC-UPT-LF assay had a detection sensitivity of 104 CFU mL−1 or 105 CFU mL−1 for each pathogen, and after sample enrichment it was 10 CFU/0.6 mg. The assay also showed good linearity, allowing quantitative detection, with a linear fitting coefficient of determination (R2) of 0.916–0.998. The 10 detection channels did not cross-react, so multiple targets could be specifically detected. When 279 real food samples were tested, the assay was highly consistent (100%) with culture-based methods. The results for 110 food samples artificially contaminated with single or multiple targets showed a high detection rate (≥80%) for most target bacteria. Overall, the TC-UPT-LF assay allows the rapid, quantitative, and simultaneous detection of 10 kinds of foodborne pathogens within 20 min, and is especially suitable for the rapid detection and surveillance of foodborne pathogens in food and water. PMID:26884128

Rapid multiplex detection of 10 foodborne pathogens with an up-converting phosphor technology-based 10-channel lateral flow assay.

PubMed

Zhao, Yong; Wang, Haoran; Zhang, Pingping; Sun, Chongyun; Wang, Xiaochen; Wang, Xinrui; Yang, Ruifu; Wang, Chengbin; Zhou, Lei

2016-02-17

The rapid high-throughput detection of foodborne pathogens is essential in controlling food safety. In this study, a 10-channel up-converting phosphor technology-based lateral flow (TC-UPT-LF) assay was established for the rapid and simultaneous detection of 10 epidemic foodborne pathogens. Ten different single-target UPT-LF strips were developed and integrated into one TC-UPT-LF disc with optimization. Without enrichment the TC-UPT-LF assay had a detection sensitivity of 10(4) CFU mL(-1) or 10(5) CFU mL(-1) for each pathogen, and after sample enrichment it was 10 CFU/0.6 mg. The assay also showed good linearity, allowing quantitative detection, with a linear fitting coefficient of determination (R(2)) of 0.916-0.998. The 10 detection channels did not cross-react, so multiple targets could be specifically detected. When 279 real food samples were tested, the assay was highly consistent (100%) with culture-based methods. The results for 110 food samples artificially contaminated with single or multiple targets showed a high detection rate (≥ 80%) for most target bacteria. Overall, the TC-UPT-LF assay allows the rapid, quantitative, and simultaneous detection of 10 kinds of foodborne pathogens within 20 min, and is especially suitable for the rapid detection and surveillance of foodborne pathogens in food and water.

Parallel evolution of Streptococcus pneumoniae and Streptococcus mitis to pathogenic and mutualistic lifestyles.

PubMed

Kilian, Mogens; Riley, David R; Jensen, Anders; Brüggemann, Holger; Tettelin, Hervé

2014-07-22

The bacterium Streptococcus pneumoniae is one of the leading causes of fatal infections affecting humans. Intriguingly, phylogenetic analysis shows that the species constitutes one evolutionary lineage in a cluster of the otherwise commensal Streptococcus mitis strains, with which humans live in harmony. In a comparative analysis of 35 genomes, including phylogenetic analyses of all predicted genes, we have shown that the pathogenic pneumococcus has evolved into a master of genomic flexibility while lineages that evolved into the nonpathogenic S. mitis secured harmonious coexistence with their host by stabilizing an approximately 15%-reduced genome devoid of many virulence genes. Our data further provide evidence that interspecies gene transfer between S. pneumoniae and S. mitis occurs in a unidirectional manner, i.e., from S. mitis to S. pneumoniae. Import of genes from S. mitis and other mitis, anginosus, and salivarius group streptococci ensured allelic replacements and antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae. Our study explains how the unique structural diversity of the pneumococcal capsule emerged and conceivably will continue to increase and reveals a striking example of the fragile border between the commensal and pathogenic lifestyles. While genomic plasticity enabling quick adaptation to environmental stress is a necessity for the pathogenic streptococci, the commensal lifestyle benefits from stability. Importance: One of the leading causes of fatal infections affecting humans, Streptococcus pneumoniae, and the commensal Streptococcus mitis are closely related obligate symbionts associated with hominids. Faced with a shortage of accessible hosts, the two opposing lifestyles evolved in parallel. We have shown that the nonpathogenic S. mitis secured harmonious coexistence with its host by stabilizing a reduced genome devoid of many virulence genes. Meanwhile, the pathogenic pneumococcus evolved into a master of genomic flexibility and imports genes from S. mitis and other related streptococci. This process ensured antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae, which conceivably will continue to increase and present a challenge to disease prevention. Copyright © 2014 Kilian et al.

Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis

PubMed Central

Starikova, Irina; Al-Haroni, Mohammed; Werner, Guido; Roberts, Adam P.; Sørum, Vidar; Nielsen, Kaare M.; Johnsen, Pål J.

2013-01-01

Objectives To determine the fitness effects of various mobile genetic elements (MGEs) in Enterococcus faecium and Enterococcus faecalis when newly acquired. We also tested the hypothesis that the biological cost of vancomycin resistance plasmids could be mitigated during continuous growth in the laboratory. Methods Different MGEs, including two conjugative transposons (CTns) of the Tn916 family (18 and 33 kb), a pathogenicity island (PAI) of 200 kb and vancomycin-resistance (vanA) plasmids (80–200 kb) of various origins and classes, were transferred into common ancestral E. faecium and E. faecalis strains by conjugation assays and experimentally evolved (vanA plasmids only). Transconjugants were characterized by PFGE, S1 nuclease assays and Southern blotting hybridization analyses. Single specific primer PCR was performed to determine the target sites for the insertion of the CTns. The fitness costs of various MGEs in E. faecium and E. faecalis were estimated in head-to-head competition experiments, and evolved populations were generated in serial transfer assays. Results The biological cost of a newly acquired PAI and two CTns were both host- and insertion-locus-dependent. Newly acquired vanA plasmids may severely reduce host fitness (25%–27%), but these costs were rapidly mitigated after only 400 generations of continuous growth in the absence of antibiotic selection. Conclusions Newly acquired MGEs may impose an immediate biological cost in E. faecium. However, as demonstrated for vanA plasmids, the initial costs of MGE carriage may be mitigated during growth and beneficial plasmid–host association can rapidly emerge. PMID:23833178

Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

PubMed Central

Rockenbach, Kate; Havird, Justin C.; Monroe, J. Grey; Triant, Deborah A.; Taylor, Douglas R.; Sloan, Daniel B.

2016-01-01

Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastid–nuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid–nuclear conflict as a novel cause of accelerated evolution. PMID:27707788

Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages

PubMed Central

Vieira, Marcos C; Zinder, Daniel; Cobey, Sarah

2018-01-01

Abstract High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable “hotspot” motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza. PMID:29688540

Analysis of expression in the Anopheles gambiae developing testes reveals rapidly evolving lineage-specific genes in mosquitoes.

PubMed

Krzywinska, Elzbieta; Krzywinski, Jaroslaw

2009-07-06

Male mosquitoes do not feed on blood and are not involved in delivery of pathogens to humans. Consequently, they are seldom the subjects of research, which results in a very poor understanding of their biology. To gain insights into male developmental processes we sought to identify genes transcribed exclusively in the reproductive tissues of male Anopheles gambiae pupae. Using a cDNA subtraction strategy, five male-specifically or highly male-biased expressed genes were isolated, four of which remain unannotated in the An. gambiae genome. Spatial and temporal expression patterns suggest that each of these genes is involved in the mid-late stages of spermatogenesis. Their sequences are rapidly evolving; however, two genes possess clear homologs in a wide range of taxa and one of these probably acts in a sperm motility control mechanism conserved in many organisms, including humans. The other three genes have no match to sequences from non-mosquito taxa, thus can be regarded as orphans. RNA in situ hybridization demonstrated that one of the orphans is transcribed in spermatids, which suggests its involvement in sperm maturation. Two other orphans have unknown functions. Expression analysis of orthologs of all five genes indicated that male-biased transcription was not conserved in the majority of cases in Aedes and Culex. Discovery of testis-expressed orphan genes in mosquitoes opens new prospects for the development of innovative control methods. The orphan encoded proteins may represent unique targets of selective anti-mosquito sterilizing agents that will not affect non-target organisms.

Genome sequence and virulence variation-related transcriptome profiles of Curvularia lunata, an important maize pathogenic fungus.

PubMed

Gao, Shigang; Li, Yaqian; Gao, Jinxin; Suo, Yujuan; Fu, Kehe; Li, Yingying; Chen, Jie

2014-07-24

Curvularia lunata is an important maize foliar fungal pathogen that distributes widely in maize growing area in China. Genome sequencing of the pathogen will provide important information for globally understanding its virulence mechanism. We report the genome sequences of a highly virulent C. lunata strain. Phylogenomic analysis indicates that C. lunata was evolved from Bipolaris maydis (Cochliobolus heterostrophus). The highly virulent strain has a high potential to evolve into other pathogenic stains based on analyses on transposases and repeat-induced point mutations. C. lunata has a smaller proportion of secreted proteins as well as B. maydis than entomopathogenic fungi. C. lunata and B. maydis have a similar proportion of protein-encoding genes highly homologous to experimentally proven pathogenic genes from pathogen-host interaction database. However, relative to B. maydis, C. lunata possesses not only many expanded protein families including MFS transporters, G-protein coupled receptors, protein kinases and proteases for transport, signal transduction or degradation, but also many contracted families including cytochrome P450, lipases, glycoside hydrolases and polyketide synthases for detoxification, hydrolysis or secondary metabolites biosynthesis, which are expected to be crucial for the fungal survival in varied stress environments. Comparative transcriptome analysis between a lowly virulent C. lunata strain and its virulence-increased variant induced by resistant host selection reveals that the virulence increase of the pathogen is related to pathways of toxin and melanin biosynthesis in stress environments, and that the two pathways probably have some overlaps. The data will facilitate a full revelation of pathogenic mechanism and a better understanding of virulence differentiation of C. lunata.

Evolution of Cost-Free Resistance under Fluctuating Drug Selection in Pseudomonas aeruginosa

PubMed Central

McCloskey, Nicholas; Hinz, Aaron J.; Dettman, Jeremy; Kassen, Rees

2017-01-01

ABSTRACT Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa under conditions of constant and fluctuating antibiotic delivery patterns. We found that high-fitness, resistant strains evolved readily under fluctuating but not constant antibiotic conditions and that their evolution was underlain by a trade-off between resistance and fitness. Whole-genome sequencing of evolved isolates revealed that resistance was gained through mutations in known resistance genes and that second-site mutations generally compensated for costs associated with resistance in the fluctuating treatment, leading to the evolution of cost-free resistance. Our results suggest that current therapies involving intermittent administration of antibiotics are contributing to the maintenance of antibiotic resistance at high levels in clinical settings. IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide. PMID:28744479

Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

PubMed

Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

2017-04-01

We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

Accelerating dynamic genetic conservation efforts: Use of FT-IR spectroscopy for the rapid identification of trees resistant to destructive pathogens

Treesearch

C. Villari; R.A. Sniezko; L.E. Rodriguez-Saona; P. Bonello

2017-01-01

A strong focus on tree germplasm that can resist threats such as non-native insects and pathogens, or a changing climate, is fundamental for successful genetic conservation efforts. However, the unavailability of tools for rapid screening of tree germplasm for resistance to critical pathogens and insect pests is becoming an increasingly serious bottleneck. Here we...

Mycobacterium abscessus Phospholipase C Expression Is Induced during Coculture within Amoebae and Enhances M. abscessus Virulence in Mice

PubMed Central

Bakala N'Goma, Jean Claude; Le Moigne, Vincent; Soismier, Nathalie; Laencina, Laura; Le Chevalier, Fabien; Roux, Anne-Laure; Poncin, Isabelle; Serveau-Avesque, Carole; Rottman, Martin; Gaillard, Jean-Louis; Etienne, Gilles; Brosch, Roland; Canaan, Stéphane

2014-01-01

Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555, encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis. Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus. Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria. PMID:25486995

Exosome-Mediated Pathogen Transmission by Arthropod Vectors.

PubMed

Hackenberg, Michael; Kotsyfakis, Michail

2018-04-24

Recent molecular and cellular studies have highlighted a potentially important role for tick exosomes in parasite transmission. Here we summarize evolving hypotheses about the largely unknown cellular events that may take place at the tick-host-pathogen interface, focusing on a potential role for arthropod exosomes in this tripartite interaction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets

USDA-ARS?s Scientific Manuscript database

Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A (H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, num...

Pathogens: raft hijackers.

PubMed

Mañes, Santos; del Real, Gustavo; Martínez-A, Carlos

2003-07-01

Throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. At the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. Pathogens have evolved many strategies to ensure their own survival and to evade the host immune system, in some cases by hijacking rafts. However, understanding the means by which pathogens exploit rafts might lead to new therapeutic strategies to prevent or alleviate certain infectious diseases, such as those caused by HIV-1 or Ebola virus.

Biological characterization of highly pathogenic avian influenza H5N1 viruses that infected humans in Egypt in 2014-2015.

PubMed

El-Shesheny, Rabeh; Mostafa, Ahmed; Kandeil, Ahmed; Mahmoud, Sara H; Bagato, Ola; Naguib, Amel; Refaey, Samir El; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

2017-03-01

Highly pathogenic avian influenza (HPAI) H5N1 influenza viruses emerged as a human pathogen in 1997 with expected potential to undergo sustained human-to-human transmission and pandemic viral spread. HPAI H5N1 is endemic in Egyptian poultry and has caused sporadic human infection. The first outbreak in early 2006 was caused by clade 2.2 viruses that rapidly evolved genetically and antigenically. A sharp increase in the number of human cases was reported in Egypt in the 2014/2015 season. In this study, we analyzed and characterized three isolates of HPAI H5N1 viruses isolated from infected humans in Egypt in 2014/2015. Phylogenetic analysis demonstrated that the nucleotide sequences of eight segments of the three isolates were clustered with those of members of clade 2.2.1.2. We also found that the human isolates from 2014/2015 had a slight, non-significant difference in their affinity for human-like sialic acid receptors. In contrast, they showed significant differences in their replication kinetics in MDCK, MDCK-SIAT, and A549 cells as well as in embryonated chicken eggs. An antiviral bioassay study revealed that all of the isolates were susceptible to amantadine. Therefore, further investigation and monitoring is required to correlate the genetic and/or antigenic changes of the emerging HPAI H5N1 viruses with possible alteration in their characteristics and their potential to become a further threat to public health.

Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host.

PubMed

Klemm, Elizabeth J; Gkrania-Klotsas, Effrossyni; Hadfield, James; Forbester, Jessica L; Harris, Simon R; Hale, Christine; Heath, Jennifer N; Wileman, Thomas; Clare, Simon; Kane, Leanne; Goulding, David; Otto, Thomas D; Kay, Sally; Doffinger, Rainer; Cooke, Fiona J; Carmichael, Andrew; Lever, Andrew Ml; Parkhill, Julian; MacLennan, Calman A; Kumararatne, Dinakantha; Dougan, Gordon; Kingsley, Robert A

2016-03-01

Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts 1 . Host adaptation can potentially progress to host restriction where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidal Salmonella infection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borne Salmonella enterica serotype Enteritidis ( S . Enteritidis) infection covering 15 years in an interleukin (IL)-12 β-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infecting S. Enteritidis harbored a mutation in the mismatch repair gene mutS that accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.

Sequence Exchange between Homologous NB-LRR Genes Converts Virus Resistance into Nematode Resistance, and Vice Versa1[OPEN

PubMed Central

Koropacka, Kamila; Roosien, Jan; Dees, Robert; Overmars, Hein; van Schaik, Casper; Pomp, Rikus; Bouwman, Liesbeth; Helder, Johannes; Bakker, Jaap; Smant, Geert

2017-01-01

Plants have evolved a limited repertoire of NB-LRR disease resistance (R) genes to protect themselves against myriad pathogens. This limitation is thought to be counterbalanced by the rapid evolution of NB-LRR proteins, as only a few sequence changes have been shown to be sufficient to alter resistance specificities toward novel strains of a pathogen. However, little is known about the flexibility of NB-LRR R genes to switch resistance specificities between phylogenetically unrelated pathogens. To investigate this, we created domain swaps between the close homologs Gpa2 and Rx1, which confer resistance in potato (Solanum tuberosum) to the cyst nematode Globodera pallida and Potato virus X, respectively. The genetic fusion of the CC-NB-ARC of Gpa2 with the LRR of Rx1 (Gpa2CN/Rx1L) results in autoactivity, but lowering the protein levels restored its specific activation response, including extreme resistance to Potato virus X in potato shoots. The reciprocal chimera (Rx1CN/Gpa2L) shows a loss-of-function phenotype, but exchange of the first three LRRs of Gpa2 by the corresponding region of Rx1 was sufficient to regain a wild-type resistance response to G. pallida in the roots. These data demonstrate that exchanging the recognition moiety in the LRR is sufficient to convert extreme virus resistance in the leaves into mild nematode resistance in the roots, and vice versa. In addition, we show that the CC-NB-ARC can operate independently of the recognition specificities defined by the LRR domain, either aboveground or belowground. These data show the versatility of NB-LRR genes to generate resistance to unrelated pathogens with completely different lifestyles and routes of invasion. PMID:28747428

Sequence Exchange between Homologous NB-LRR Genes Converts Virus Resistance into Nematode Resistance, and Vice Versa.

PubMed

Slootweg, Erik; Koropacka, Kamila; Roosien, Jan; Dees, Robert; Overmars, Hein; Lankhorst, Rene Klein; van Schaik, Casper; Pomp, Rikus; Bouwman, Liesbeth; Helder, Johannes; Schots, Arjen; Bakker, Jaap; Smant, Geert; Goverse, Aska

2017-09-01

Plants have evolved a limited repertoire of NB-LRR disease resistance ( R ) genes to protect themselves against myriad pathogens. This limitation is thought to be counterbalanced by the rapid evolution of NB-LRR proteins, as only a few sequence changes have been shown to be sufficient to alter resistance specificities toward novel strains of a pathogen. However, little is known about the flexibility of NB-LRR R genes to switch resistance specificities between phylogenetically unrelated pathogens. To investigate this, we created domain swaps between the close homologs Gpa2 and Rx1 , which confer resistance in potato ( Solanum tuberosum ) to the cyst nematode Globodera pallida and Potato virus X , respectively. The genetic fusion of the CC-NB-ARC of Gpa2 with the LRR of Rx1 (Gpa2 CN /Rx1 L ) results in autoactivity, but lowering the protein levels restored its specific activation response, including extreme resistance to Potato virus X in potato shoots. The reciprocal chimera (Rx1 CN /Gpa2 L ) shows a loss-of-function phenotype, but exchange of the first three LRRs of Gpa2 by the corresponding region of Rx1 was sufficient to regain a wild-type resistance response to G. pallida in the roots. These data demonstrate that exchanging the recognition moiety in the LRR is sufficient to convert extreme virus resistance in the leaves into mild nematode resistance in the roots, and vice versa. In addition, we show that the CC-NB-ARC can operate independently of the recognition specificities defined by the LRR domain, either aboveground or belowground. These data show the versatility of NB-LRR genes to generate resistance to unrelated pathogens with completely different lifestyles and routes of invasion. © 2017 American Society of Plant Biologists. All Rights Reserved.

Extending the the behavioral immune system to political psychology: are political conservatism and disgust sensitivity really related?

PubMed

Tybur, Joshua M; Merriman, Leslie A; Hooper, Ann E Caldwell; McDonald, Melissa M; Navarrete, Carlos David

2010-10-26

Previous research suggests that several individual and cultural level attitudes, cognitions, and societal structures may have evolved to mitigate the pathogen threats posed by intergroup interactions. It has been suggested that these anti-pathogen defenses are at the root of conservative political ideology. Here, we test a hypothesis that political conservatism functions as a pathogen-avoidance strategy. Across three studies, we consistently find no relationship between sensitivity to pathogen disgust and multiple measures of political conservatism. These results are contrasted with theoretical perspectives suggesting a relationship between conservatism and pathogen avoidance, and with previous findings of a relationship between conservatism and disgust sensitivity.

Two distinct secretion systems facilitate tissue invasion by the rice blast fungus Magnaporthe oryzae

PubMed Central

Giraldo, Martha C.; Dagdas, Yasin F.; Gupta, Yogesh K.; Mentlak, Thomas A.; Yi, Mihwa; Martinez-Rocha, Ana Lilia; Saitoh, Hiromasa; Terauchi, Ryohei; Talbot, Nicholas J.; Valent, Barbara

2013-01-01

To cause plant diseases, pathogenic micro-organisms secrete effector proteins into host tissue to suppress immunity and support pathogen growth. Bacterial pathogens have evolved several distinct secretion systems to target effector proteins, but whether fungi, which cause the major diseases of most crop species, also require different secretory mechanisms is not known. Here we report that the rice blast fungus Magnaporthe oryzae possesses two distinct secretion systems to target effectors during plant infection. Cytoplasmic effectors, which are delivered into host cells, preferentially accumulate in the biotrophic interfacial complex, a novel plant membrane-rich structure associated with invasive hyphae. We show that the biotrophic interfacial complex is associated with a novel form of secretion involving exocyst components and the Sso1 t-SNARE. By contrast, effectors that are secreted from invasive hyphae into the extracellular compartment follow the conventional secretory pathway. We conclude that the blast fungus has evolved distinct secretion systems to facilitate tissue invasion. PMID:23774898

Developing Collective Learning Extension for Rapidly Evolving Information System Courses

ERIC Educational Resources Information Center

Agarwal, Nitin; Ahmed, Faysal

2017-01-01

Due to rapidly evolving Information System (IS) technologies, instructors find themselves stuck in the constant game of catching up. On the same hand students find their skills obsolete almost as soon as they graduate. As part of IS curriculum and education, we need to emphasize more on teaching the students "how to learn" while keeping…

Reoccurrence of H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses in wild birds during 2016

USDA-ARS?s Scientific Manuscript database

The Asian-origin H5N1 A/goose/Guangdong/1/1996 (Gs/GD) lineage of high pathogenicity avian influenza viruses (HPAIV) has become widespread across four continents, affecting poultry, wild birds and humans. H5N1 HPAIV has evolved into multiple hemagglutinin (HA) genetic clades and reassorting with dif...

Root diseases: primary agents and secondary consequences of disturbance

Treesearch

William J. Otrosina; George T. Ferrell

1995-01-01

The fact that endemic root disease causing pathogens have evolved with forest ecosystems does not necessarily mean they are inconsequential. A pathogen such as the P group of Heterobasidion annosum has become an intractable problem in many Sierra east side pine stands in California because the fungus is adapted to colonization of freshly cut stump surfaces. The S group...

RapTOR: Automated Sequencing Library Preparation and Suppression for Rapid Pathogen Characterization (7th Annual SFAF Meeting, 2012)

ScienceCinema

Lane, Todd

2018-05-18

Todd Lane on "RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Effect of immunomagnetic bead size on recovery of foodborne pathogenic bacteria

USDA-ARS?s Scientific Manuscript database

Long culture enrichment is currently a speed-limiting step in both traditional and rapid detection techniques for foodborne pathogens. Immunomagnetic separation (IMS) as a culture-free enrichment sample preparation technique has gained increasing popularity in the development of rapid detection met...

RapTOR: Automated Sequencing Library Preparation and Suppression for Rapid Pathogen Characterization (7th Annual SFAF Meeting, 2012)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lane, Todd

2012-06-01

Todd Lane on "RapTOR: Automated sequencing library preparation and suppression for rapid pathogen characterization" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery

PubMed Central

Wright, Peter M.; Seiple, Ian B.; Myers, Andrew G.

2015-01-01

The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chemical synthesis to antibacterial drug discovery must play a critical role if a crisis of global proportions is to be averted. PMID:24990531

Antimicrobial Functions of Lactoferrin Promote Genetic Conflicts in Ancient Primates and Modern Humans.

PubMed

Barber, Matthew F; Kronenberg, Zev; Yandell, Mark; Elde, Nels C

2016-05-01

Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with microbes remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long-term antagonism by bacteria. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with opportunistic bacterial pathogens causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions.

Mechanisms and pathways of Toxoplasma gondii transepithelial migration

PubMed Central

Jones, Emily J.; Carding, Simon R.

2017-01-01

ABSTRACT Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite. PMID:28452683

Mechanisms and pathways of Toxoplasma gondii transepithelial migration.

PubMed

Jones, Emily J; Korcsmaros, Tamas; Carding, Simon R

2017-01-02

Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established. It has recently been proposed that parasite interactions with the integral tight junction (TJ) protein occludin influences parasite transmigration of the intestinal epithelium. We review here the emerging mechanisms of T. gondii transmigration of the small intestinal epithelium alongside the developing role played in modulating the wider TJ-associated proteome to rewire host cell regulatory systems for the benefit of the parasite.

Isolation and Flow Cytometry Analysis of Innate Lymphoid Cells from the Intestinal Lamina Propria.

PubMed

Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

2017-01-01

The intestinal mucosa constitutes the biggest surface area of the body. It is constantly challenged by bacteria, commensal and pathogenic, protozoa, and food-derived irritants. In order to maintain homeostasis, a complex network of signaling circuits has evolved that includes contributions of immune cells. In recent years a subset of lymphocytes, which belong to the innate immune system, has caught particular attention. These so-called innate lymphoid cells (ILC) reside within the lamina propria of the small and large intestines and rapidly respond to environmental challenges. They provide immunity to various types of infections but may also contribute to organ homeostasis as they produce factors acting on epithelial cells thereby enhancing barrier integrity. Here, we describe how these cells can be isolated from their environment and provide an in-depth protocol how to visualize the various ILC subsets by flow cytometry.

Chemodetection and Destruction of Host Urea Allows Helicobacter pylori to Locate the Epithelium

PubMed Central

Huang, Julie Y.; Sweeney, Emily Goers; Sigal, Michael; Zhang, Hai C.; Remington, S. James; Cantrell, Michael A.; Kuo, Calvin J.; Guillemin, Karen; Amieva, Manuel R.

2015-01-01

SUMMARY The gastric pathogen Helicobacter pylori interacts intimately with the gastric mucosa to avoid the microbicidal acid in the stomach lumen. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. We show that metabolites emanating from human gastric organoids rapidly attract H. pylori. This response is largely controlled by the bacterial chemoreceptor TlpB, and the main attractant emanating from epithelia is urea. Our previous structural analyses show that TlpB binds urea with high affinity. Here we demonstrate that this tight binding controls highly sensitive responses, allowing detection of urea concentrations as low as 50 nanomolar. Attraction to urea requires that H. pylori urease simultaneously destroys the signal. We propose that H. pylori has evolved a sensitive urea chemodetection and destruction system that allows the bacterium to dynamically and locally modify the host environment to locate the epithelium. PMID:26269952

The antibiotic resistome.

PubMed

Wright, Gerard D

2010-08-01

Antibiotics are essential for the treatment of bacterial infections and are among our most important drugs. Resistance has emerged to all classes of antibiotics in clinical use. Antibiotic resistance has, proven inevitable and very often it emerges rapidly after the introduction of a drug into the clinic. There is, therefore, a great interest in understanding the origins, scope and evolution of antibiotic resistance. The review discusses the concept of the antibiotic resistome, which is the collection of all genes that directly or indirectly contribute to antibiotic resistance. The review seeks to assemble current knowledge of the resistome concept as a means of understanding the totality of resistance and not just resistance in pathogenic bacteria. The concept of the antibiotic resistome provides a framework for the study and understanding of how resistance emerges and evolves. Furthermore, the study of the resistome reveals strategies that can be applied in new antibiotic discoveries.

Longevity extension by phytochemicals.

PubMed

Leonov, Anna; Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Lutchman, Vicky; Medkour, Younes; Titorenko, Vladimir I

2015-04-13

Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field.

Field Demonstration of a Multiplexed Point-of-Care Diagnostic Platform for Plant Pathogens.

PubMed

Lau, Han Yih; Wang, Yuling; Wee, Eugene J H; Botella, Jose R; Trau, Matt

2016-08-16

Effective disease management strategies to prevent catastrophic crop losses require rapid, sensitive, and multiplexed detection methods for timely decision making. To address this need, a rapid, highly specific and sensitive point-of-care method for multiplex detection of plant pathogens was developed by taking advantage of surface-enhanced Raman scattering (SERS) labeled nanotags and recombinase polymerase amplification (RPA), which is a rapid isothermal amplification method with high specificity. In this study, three agriculturally important plant pathogens (Botrytis cinerea, Pseudomonas syringae, and Fusarium oxysporum) were used to demonstrate potential translation into the field. The RPA-SERS method was faster, more sensitive than polymerase chain reaction, and could detect as little as 2 copies of B. cinerea DNA. Furthermore, multiplex detection of the three pathogens was demonstrated for complex systems such as the Arabidopsis thaliana plant and commercial tomato crops. To demonstrate the potential for on-site field applications, a rapid single-tube RPA/SERS assay was further developed and successfully performed for a specific target outside of a laboratory setting.

Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

PubMed

Zauberman, Ayelet; Tidhar, Avital; Levy, Yinon; Bar-Haim, Erez; Halperin, Gideon; Flashner, Yehuda; Cohen, Sara; Shafferman, Avigdor; Mamroud, Emanuelle

2009-06-16

An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7)-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50) of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the virulence strategies of Y. pestis in nature.

[Rapid identification of meningitis due to bacterial pathogens].

PubMed

Ubukata, Kimiko

2013-01-01

We constructed a new real-time PCR method to detect causative pathogens in cerebrospinal fluid (CSF) from patient due to bacterial meningitis. The eight pathogens targeted in the PCR are Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus agalactiae, Staphylococcus aurues, Neisseria meningitides, Listeria monocytogenes, Esherichia coli, and Mycoplasma pneumoniae. The total time from DNA extraction from CSF to PCR analysis was 1.5 hour. The pathogens were detected in 72% of the CSF samples (n=115) by real-time PCR, but in only 48% by culture, although the microorganisms were completely concordant. The detection rate of pathogens with PCR was significantly better than that with cultures in patients with antibiotic administration.In conclusion, detection with real-time PCR is useful for rapidly identifying the causative pathogens of meningitis and for examining the clinical course of chemotherapy.

Sensitizing pathogens to antibiotics using the CRISPR-Cas system.

PubMed

Goren, Moran; Yosef, Ido; Qimron, Udi

2017-01-01

The extensive use of antibiotics over the last century has resulted in a significant artificial selection pressure for antibiotic-resistant pathogens to evolve. Various strategies to fight these pathogens have been introduced including new antibiotics, naturally-derived enzymes/peptides that specifically target pathogens and bacteriophages that lyse these pathogens. A new tool has recently been introduced in the fight against drug-resistant pathogens-the prokaryotic defense mechanism-clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system. The CRISPR-Cas system acts as a nuclease that can be guided to cleave any target DNA, allowing sophisticated, yet feasible, manipulations of pathogens. Here, we review pioneering studies that use the CRISPR-Cas system to specifically edit bacterial populations, eliminate their resistance genes and combine these two strategies in order to produce an artificial selection pressure for antibiotic-sensitive pathogens. We suggest that intelligent design of this system, along with efficient delivery tools into pathogens, may significantly reduce the threat of antibiotic-resistant pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

RAPID MONITORING BY QPCR FOR PATHOGENIC ASPERGILLUS DURING CARPET REMOVAL FROM A HOSPITAL

EPA Science Inventory

Monitoring for pathogenic Aspergillus species using a rapid, highly sensitive, quantitative polymerase chain reaction technique during carpet removal in a burn unit provided data which allowed the patients to be safely returned to the re-floored area sooner than if only conventi...

Threats and opportunities of plant pathogenic bacteria.

PubMed

Tarkowski, Petr; Vereecke, Danny

2014-01-01

Plant pathogenic bacteria can have devastating effects on plant productivity and yield. Nevertheless, because these often soil-dwelling bacteria have evolved to interact with eukaryotes, they generally exhibit a strong adaptivity, a versatile metabolism, and ingenious mechanisms tailored to modify the development of their hosts. Consequently, besides being a threat for agricultural practices, phytopathogens may also represent opportunities for plant production or be useful for specific biotechnological applications. Here, we illustrate this idea by reviewing the pathogenic strategies and the (potential) uses of five very different (hemi)biotrophic plant pathogenic bacteria: Agrobacterium tumefaciens, A. rhizogenes, Rhodococcus fascians, scab-inducing Streptomyces spp., and Pseudomonas syringae. Copyright © 2013 Elsevier Inc. All rights reserved.

Community acquired methicillin resistant Staphylococcus aureus pneumonia: an update for the emergency and intensive care physician.

PubMed

Karampela, I; Poulakou, G; Dimopoulos, G

2012-08-01

Pneumonia caused by community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) among individuals without healthcare-associated (HA) risk factors was first recognized a decade ago. CA-MRSA has now been established as a pathogen responsible for rapidly progressive, frequently fatal disease manifesting as necrotizing pneumonia, severe sepsis and necrotizing fasciitis. The frequency of occurrence, risk factors, and optimal treatment of CA-MRSA pneumonia remain unclear and vary significantly across countries. CA-MRSA is resistant to β-lactam antimicrobials due to the acquisition of novel methicillin resistance genetic cassettes. Additionally many CA-MRSA strains produce Panton-Valentine leukocidin (PVL), due to which they probably exceed the virulence of hospital-acquired MRSA isolates (HA-MRSA). CA-MRSA pneumonia requires early suspicion -especially in young otherwise healthy individuals with rapidly evolving clinical picture presenting with cavitary consolidation, bilateral infiltrates, pleural effusion and hemoptysis. Prompt hospitalization and aggressive treatment with intravenous antibiotics is warranted to improve outcomes. Therapeutic approach for severe CA-MRSA infections and particularly pneumonia is generally the same as that for invasive HA-MRSA infections. New anti-MRSA agents and possible combinations are of great importance to be evaluated in the future.

Specific and Sensitive Isothermal Electrochemical Biosensor for Plant Pathogen DNA Detection with Colloidal Gold Nanoparticles as Probes

NASA Astrophysics Data System (ADS)

Lau, Han Yih; Wu, Haoqi; Wee, Eugene J. H.; Trau, Matt; Wang, Yuling; Botella, Jose R.

2017-01-01

Developing quick and sensitive molecular diagnostics for plant pathogen detection is challenging. Herein, a nanoparticle based electrochemical biosensor was developed for rapid and sensitive detection of plant pathogen DNA on disposable screen-printed carbon electrodes. This 60 min assay relied on the rapid isothermal amplification of target pathogen DNA sequences by recombinase polymerase amplification (RPA) followed by gold nanoparticle-based electrochemical assessment with differential pulse voltammetry (DPV). Our method was 10,000 times more sensitive than conventional polymerase chain reaction (PCR)/gel electrophoresis and could readily identify P. syringae infected plant samples even before the disease symptoms were visible. On the basis of the speed, sensitivity, simplicity and portability of the approach, we believe the method has potential as a rapid disease management solution for applications in agriculture diagnostics.

Specific and Sensitive Isothermal Electrochemical Biosensor for Plant Pathogen DNA Detection with Colloidal Gold Nanoparticles as Probes.

PubMed

Lau, Han Yih; Wu, Haoqi; Wee, Eugene J H; Trau, Matt; Wang, Yuling; Botella, Jose R

2017-01-17

Developing quick and sensitive molecular diagnostics for plant pathogen detection is challenging. Herein, a nanoparticle based electrochemical biosensor was developed for rapid and sensitive detection of plant pathogen DNA on disposable screen-printed carbon electrodes. This 60 min assay relied on the rapid isothermal amplification of target pathogen DNA sequences by recombinase polymerase amplification (RPA) followed by gold nanoparticle-based electrochemical assessment with differential pulse voltammetry (DPV). Our method was 10,000 times more sensitive than conventional polymerase chain reaction (PCR)/gel electrophoresis and could readily identify P. syringae infected plant samples even before the disease symptoms were visible. On the basis of the speed, sensitivity, simplicity and portability of the approach, we believe the method has potential as a rapid disease management solution for applications in agriculture diagnostics.

Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

PubMed

Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

2011-09-01

Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

Rapid detection, characterization, and enumeration of foodborne pathogens.

PubMed

Hoorfar, J

2011-11-01

As food safety management further develops, microbiological testing will continue to play an important role in assessing whether Food Safety Objectives are achieved. However, traditional microbiological culture-based methods are limited, particularly in their ability to provide timely data. The present review discusses the reasons for the increasing interest in rapid methods, current developments in the field, the research needs, and the future trends. The advent of biotechnology has introduced new technologies that led to the emergence of rapid diagnostic methods and altered food testing practices. Rapid methods are comprised of many different detection technologies, including specialized enzyme substrates, antibodies and DNA, ranging from simple differential plating media to the use of sophisticated instruments. The use of non-invasive sampling techniques for live animals especially came into focus with the 1990s outbreak of bovine spongiform encephalopathy that was linked to the human outbreak of Creutzfeldt Jakob's Disease. Serology is still an important tool in preventing foodborne pathogens to enter the human food supply through meat and milk from animals. One of the primary uses of rapid methods is for fast screening of large number of samples, where most of them are expected to be test-negative, leading to faster product release for sale. This has been the main strength of rapid methods such as real-time Polymerase Chain Reaction (PCR). Enrichment PCR, where a primary culture broth is tested in PCR, is the most common approach in rapid testing. Recent reports show that it is possible both to enrich a sample and enumerate by pathogen-specific real-time PCR, if the enrichment time is short. This can be especially useful in situations where food producers ask for the level of pathogen in a contaminated product. Another key issue is automation, where the key drivers are miniaturization and multiple testing, which mean that not only one instrument is flexible enough to test for many pathogens but also many pathogens can be detected with one test. The review is mainly based on the author's scientific work that has contributed with the following new developments to this field: (i) serologic tests for large-scale screening, surveillance, or eradication programs, (ii) same-day detection of Salmonella that otherwise was considered as difficult to achieve, (iii) pathogen enumeration following a short log-phase enrichment, (iv) detection of foodborne pathogens in air samples, and finally (v) biotracing of pathogens based on mathematical modeling, even in the absence of isolate. Rapid methods are discussed in a broad global health perspective, international food supply, and for improvement of quantitative microbial risk assessments. The need for quantitative sample preparation techniques, culture-independent, metagenomic-based detection, online monitoring, a global validation infrastructure has been emphasized. The cost and ease of use of rapid assays remain challenging obstacles to surmount. © 2011 The Author. APMIS © 2011 APMIS.

Urinary tract infection: recent insight into the evolutionary arms race between uropathogenic Escherichia coli and our immune system.

PubMed

Schwab, Sebastian; Jobin, Katarzyna; Kurts, Christian

2017-12-01

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. Humans evolved various immune-dependent and independent defense mechanisms, while pathogens evolved multiple virulence factors to fight back. This article summarizes recent findings regarding the arms race between hosts and pathogens in UTIs. It was recently reported that macrophage subsets regulate neutrophil-mediated defense in primary UTIs but seem to subvert adaptive immunity upon re-infection. Moreover, some bacterial strains can survive inside macrophages, leading to recurrent infections. Inflammasome activation results in infected host cell death and pathogen release, facilitating the removal of intracellular bacteria. As a counteraction, some bacteria evolved mechanisms to disrupt inflammasome activation. Mucosal-associated invariant T cells are further effectors that can lyse infected epithelial cells and release intracellular bacteria. Once released, the bacteria are phagocytosed by neutrophils. However, some bacteria can inhibit neutrophil migration and deprive neutrophils of nutrients. Furthermore, the complement system, considered generally bactericidal, is exploited by the bacteria for cellular invasion. Another weapon against UTI is antimicrobial peptides, e.g. ribonuclease 7, but its production is inhibited by certain bacterial strains. Thus the arms race in UTI is ongoing, and knowing the enemy's methods can help in developing new drugs to win the race. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Molecular approaches for biosurveillance of the cucurbit downy mildew pathogen, Pseudoperonospora cubensis

USDA-ARS?s Scientific Manuscript database

Globalization has allowed for rapid movement of plant pathogens that threaten food security. Successful disease management largely depends in timely and accurate detection of plant pathogens causing epidemics. Thus, biosurveillance of epidemic plant pathogens such as Pseudoperonospora cubensis, the ...

Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria

PubMed Central

Band, Victor I.; Weiss, David S.

2014-01-01

Cationic antimicrobial peptides (CAMPs) are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance. PMID:25927010

RAPID MONITORING BY QUANTITATIVE POLYMERASE CHAIN REACTION FOR PATHOGENIC ASPERGILLUS DURING CARPET REMOVAL FROM A HOSPITAL

EPA Science Inventory

Monitoring for pathogenic Aspergillus species using a rapid, highly sensitive, quantitative polumerase chain reaction technique during carpet removal in a burn unit provided data which allowed the patients to be safely returned to the re-floored area sooner than if only conventio...

Surface enhanced raman spectroscopy technique in rapid detection of live and dead salmonella cells

USDA-ARS?s Scientific Manuscript database

Many research proved that Surface Enhanced Raman Spectroscopy (SERS) can detect pathogens rapidly and accurately. In this study, a silver metal substrate was used for the selected common food pathogen Salmonella typhimurium bacteria. Nano silver rods were deposited on a thin titanium coating over t...

The potential for early and rapid pathogen detection within poultry processing through hyperspectral microscopy

USDA-ARS?s Scientific Manuscript database

The acquisition of hyperspectral microscopic images containing both spatial and spectral data has shown potential for the early and rapid optical classification of foodborne pathogens. A hyperspectral microscope with a metal halide light source and acousto-optical tunable filter (AOTF) collects 89 ...

Cold plasma rapid decontamination of food contact surfaces contaminated with Salmonella biofilms

USDA-ARS?s Scientific Manuscript database

Cross-contamination of fresh produce and other foods from persistent pathogen reservoirs is a known risk factor in processing environments. Industry requires a rapid, waterless, zero-contact, chemical-free method for removing pathogens from food-contact surfaces. Cold plasma was tested for its abili...

Surface plasmon resonance imaging for label-free detection of foodborne pathogens and toxins

USDA-ARS?s Scientific Manuscript database

More rapid and efficient detection methods for foodborne pathogenic bacteria and toxins are needed to address the long assay time and limitations in multiplex capacity. Surface plasmon resonance imaging (SPRi) is an emerging optical technique, which allows for rapid and label-free screening of multi...

A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

USDA-ARS?s Scientific Manuscript database

Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more c...

Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen).

PubMed

Rambaut, Andrew; Lam, Tommy T; Max Carvalho, Luiz; Pybus, Oliver G

2016-01-01

Gene sequences sampled at different points in time can be used to infer molecular phylogenies on a natural timescale of months or years, provided that the sequences in question undergo measurable amounts of evolutionary change between sampling times. Data sets with this property are termed heterochronous and have become increasingly common in several fields of biology, most notably the molecular epidemiology of rapidly evolving viruses. Here we introduce the cross-platform software tool, TempEst (formerly known as Path-O-Gen), for the visualization and analysis of temporally sampled sequence data. Given a molecular phylogeny and the dates of sampling for each sequence, TempEst uses an interactive regression approach to explore the association between genetic divergence through time and sampling dates. TempEst can be used to (1) assess whether there is sufficient temporal signal in the data to proceed with phylogenetic molecular clock analysis, and (2) identify sequences whose genetic divergence and sampling date are incongruent. Examination of the latter can help identify data quality problems, including errors in data annotation, sample contamination, sequence recombination, or alignment error. We recommend that all users of the molecular clock models implemented in BEAST first check their data using TempEst prior to analysis.

Pathogen evolution under host avoidance plasticity.

PubMed

McLeod, David V; Day, Troy

2015-09-07

Host resistance consists of defences that limit pathogen burden, and can be classified as either adaptations targeting recovery from infection or those focused upon infection avoidance. Conventional theory treats avoidance as a fixed strategy which does not vary from one interaction to the next. However, there is increasing empirical evidence that many avoidance strategies are triggered by external stimuli, and thus should be treated as phenotypically plastic responses. Here, we consider the implications of avoidance plasticity for host-pathogen coevolution. We uncover a number of predictions challenging current theory. First, in the absence of pathogen trade-offs, plasticity can restrain pathogen evolution; moreover, the pathogen exploits conditions in which the host would otherwise invest less in resistance, causing resistance escalation. Second, when transmission trades off with pathogen-induced mortality, plasticity encourages avirulence, resulting in a superior fitness outcome for both host and pathogen. Third, plasticity ensures the sterilizing effect of pathogens has consequences for pathogen evolution. When pathogens castrate hosts, selection forces them to minimize mortality virulence; moreover, when transmission trades off with sterility alone, resistance plasticity is sufficient to prevent pathogens from evolving to fully castrate. © 2015 The Author(s).

Detection of biomarkers of pathogenic Naegleria fowleri through mass spectrometry and proteomics.

PubMed

Moura, Hercules; Izquierdo, Fernando; Woolfitt, Adrian R; Wagner, Glauber; Pinto, Tatiana; del Aguila, Carmen; Barr, John R

2015-01-01

Emerging methods based on mass spectrometry (MS) can be used in the rapid identification of microorganisms. Thus far, these practical and rapidly evolving methods have mainly been applied to characterize prokaryotes. We applied matrix-assisted laser-desorption-ionization-time-of-flight mass spectrometry MALDI-TOF MS in the analysis of whole cells of 18 N. fowleri isolates belonging to three genotypes. Fourteen originated from the cerebrospinal fluid or brain tissue of primary amoebic meningoencephalitis patients and four originated from water samples of hot springs, rivers, lakes or municipal water supplies. Whole Naegleria trophozoites grown in axenic cultures were washed and mixed with MALDI matrix. Mass spectra were acquired with a 4700 TOF-TOF instrument. MALDI-TOF MS yielded consistent patterns for all isolates examined. Using a combination of novel data processing methods for visual peak comparison, statistical analysis and proteomics database searching we were able to detect several biomarkers that can differentiate all species and isolates studied, along with common biomarkers for all N. fowleri isolates. Naegleria fowleri could be easily separated from other species within the genus Naegleria. A number of peaks detected were tentatively identified. MALDI-TOF MS fingerprinting is a rapid, reproducible, high-throughput alternative method for identifying Naegleria isolates. This method has potential for studying eukaryotic agents. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

Adaptation to fluctuations in temperature by nine species of bacteria.

PubMed

Saarinen, Kati; Laakso, Jouni; Lindström, Leena; Ketola, Tarmo

2018-03-01

Rapid environmental fluctuations are ubiquitous in the wild, yet majority of experimental studies mostly consider effects of slow fluctuations on organism. To test the evolutionary consequences of fast fluctuations, we conducted nine independent experimental evolution experiments with bacteria. Experimental conditions were same for all species, and we allowed them to evolve either in fluctuating temperature alternating rapidly between 20°C and 40°C or at constant 30°C temperature. After experimental evolution, we tested the performance of the clones in both rapid fluctuation and in constant environments (20°C, 30°C and 40°C). Results from experiments on these nine species were combined meta-analytically. We found that overall the clones evolved in the fluctuating environment had evolved better efficiency in tolerating fluctuations (i.e., they had higher yield in fluctuating conditions) than the clones evolved in the constant environment. However, we did not find any evidence that fluctuation-adapted clones would have evolved better tolerance to any measured constant environments (20°C, 30°C, and 40°C). Our results back up recent empirical findings reporting that it is hard to predict adaptations to fast fluctuations using tolerance curves.

Convergent balancing selection on an antimicrobial peptide in Drosophila

PubMed Central

Unckless, Robert L.; Howick, Virginia M.; Lazzaro, Brian P.

2015-01-01

Summary Genes of the immune system often evolve rapidly and adaptively, presumably driven by antagonistic interactions with pathogens [1–4]. Those genes encoding secreted antimicrobial peptides (AMPs), however, have failed to exhibit conventional signatures of strong adaptive evolution, especially in arthropods (e.g., [5, 6]) and often segregate for null alleles and gene deletions [3, 4, 7, 8]. Furthermore, quantitative genetic studies have failed to associate naturally occurring polymorphism in AMP genes with variation in resistance to infection [9–11]. Both the lack of signatures of positive selection in AMPs and lack of association between genotype and immune phenotypes have yielded an interpretation that AMP genes evolve under relaxed evolutionary constraint, with enough functional redundancy that variation in, or even loss of, any particular peptide would have little effect on overall resistance [12, 13]. In stark contrast to the current paradigm, we identified a naturally occurring amino acid polymorphism in the antimicrobial peptide, Diptericin, that is highly predictive of resistance to bacterial infection in Drosophila melanogaster [13]. The identical amino acid polymorphism arose in parallel in the sister species D. simulans, by independent mutation with equivalent phenotypic effect. Convergent substitutions to arginine at the same amino acid residue have evolved at least five times across the Drosophila genus. We hypothesize that the alternative alleles are maintained by balancing selection through context-dependent or fluctuating selection. This pattern of evolution appears to be common in antimicrobial peptides, but is invisible to conventional screens for adaptive evolution that are predicated on elevated rates of amino acid divergence. PMID:26776733

Parallel independent evolution of pathogenicity within the genus Yersinia

PubMed Central

Reuter, Sandra; Connor, Thomas R.; Barquist, Lars; Walker, Danielle; Feltwell, Theresa; Harris, Simon R.; Fookes, Maria; Hall, Miquette E.; Petty, Nicola K.; Fuchs, Thilo M.; Corander, Jukka; Dufour, Muriel; Ringwood, Tamara; Savin, Cyril; Bouchier, Christiane; Martin, Liliane; Miettinen, Minna; Shubin, Mikhail; Riehm, Julia M.; Laukkanen-Ninios, Riikka; Sihvonen, Leila M.; Siitonen, Anja; Skurnik, Mikael; Falcão, Juliana Pfrimer; Fukushima, Hiroshi; Scholz, Holger C.; Prentice, Michael B.; Wren, Brendan W.; Parkhill, Julian; Carniel, Elisabeth; Achtman, Mark; McNally, Alan; Thomson, Nicholas R.

2014-01-01

The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens. PMID:24753568

The trans-kingdom identification of negative regulators of pathogen hypervirulence.

PubMed

Brown, Neil A; Urban, Martin; Hammond-Kosack, Kim E

2016-01-01

Modern society and global ecosystems are increasingly under threat from pathogens, which cause a plethora of human, animal, invertebrate and plant diseases. Of increasing concern is the trans-kingdom tendency for increased pathogen virulence that is beginning to emerge in natural, clinical and agricultural settings. The study of pathogenicity has revealed multiple examples of convergently evolved virulence mechanisms. Originally described as rare, but increasingly common, are interactions where a single gene deletion in a pathogenic species causes hypervirulence. This review utilised the pathogen-host interaction database (www.PHI-base.org) to identify 112 hypervirulent mutations from 37 pathogen species, and subsequently interrogates the trans-kingdom, conserved, molecular, biochemical and cellular themes that cause hypervirulence. This study investigates 22 animal and 15 plant pathogens including 17 bacterial and 17 fungal species. Finally, the evolutionary significance and trans-kingdom requirement for negative regulators of hypervirulence and the implication of pathogen hypervirulence and emerging infectious diseases on society are discussed. © FEMS 2015.

Antimicrobial peptides in the female reproductive tract: a critical component of the mucosal immune barrier with physiological and clinical implications.

PubMed

Yarbrough, Victoria L; Winkle, Sean; Herbst-Kralovetz, Melissa M

2015-01-01

At the interface of the external environment and the mucosal surface of the female reproductive tract (FRT) lies a first-line defense against pathogen invasion that includes antimicrobial peptides (AMP). Comprised of a unique class of multifunctional, amphipathic molecules, AMP employ a wide range of functions to limit microbial invasion and replication within host cells as well as independently modulate the immune system, dampen inflammation and maintain tissue homeostasis. The role of AMP in barrier defense at the level of the skin and gut has received much attention as of late. Given the far reaching implications for women's health, maternal and fetal morbidity and mortality, and sexually transmissible and polymicrobial diseases, we herein review the distribution and function of key AMP throughout the female reproductive mucosa and assess their role as an essential immunological barrier to microbial invasion throughout the reproductive cycle of a woman's lifetime. A comprehensive search in PubMed/Medline was conducted related to AMP general structure, function, signaling, expression, distribution and barrier function of AMP in the FRT, hormone regulation of AMP, the microbiome of the FRT, and AMP in relation to implantation, pregnancy, fertility, pelvic inflammatory disease, complications of pregnancy and assisted reproductive technology. AMP are amphipathic peptides that target microbes for destruction and have been conserved throughout all living organisms. In the FRT, several major classes of AMP are expressed constitutively and others are inducible at the mucosal epithelium and by immune cells. AMP expression is also under the influence of sex hormones, varying throughout the menstrual cycle, and dependent on the vaginal microbiome. AMP can prevent infection with sexually transmissible and opportunistic pathogens of the female reproductive tissues, although emerging understanding of vaginal dysbiosis suggests induction of a unique AMP profile with increased susceptibility to these pathogens. During pregnancy, AMP are key immune effectors of the fetal membranes and placenta and are dysregulated in states of intrauterine infection and other complications of pregnancy. At the level of the FRT, AMP serve to inhibit infection by sexually and vertically transmissible as well as by opportunistic bacteria, fungi, viruses, and protozoa and must do so throughout the hormone flux of menses and pregnancy. Guarding the exclusive site of reproduction, AMP modulate the vaginal microbiome of the lower FRT to aid in preventing ascending microbes into the upper FRT. Evolving in parallel with, and in response to, pathogenic insults, AMP are relatively immune to the resistance mechanisms employed by rapidly evolving pathogens and play a key role in barrier function and host defense throughout the FRT. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Disease Management in the Genomics Era-Summaries of Focus Issue Papers.

PubMed

Klosterman, S J; Rollins, J R; Sudarshana, M R; Vinatzer, B A

2016-10-01

The genomics revolution has contributed enormously to research and disease management applications in plant pathology. This development has rapidly increased our understanding of the molecular mechanisms underpinning pathogenesis and resistance, contributed novel markers for rapid pathogen detection and diagnosis, and offered further insights into the genetics of pathogen populations on a larger scale. The availability of whole genome resources coupled with next-generation sequencing (NGS) technologies has helped fuel genomics-based approaches to improve disease resistance in crops. NGS technologies have accelerated the pace at which whole plant and pathogen genomes have become available, and made possible the metagenomic analysis of plant-associated microbial communities. Furthermore, NGS technologies can now be applied routinely and cost effectively to rapidly generate plant and/or pathogen genome or transcriptome marker sequences associated with virulence phenotypes in the pathogen or resistance phenotypes in the plant, potentially leading to improvements in plant disease management. In some systems, investments in plant and pathogen genomics have led to immediate, tangible benefits. This focus issue covers some of the systems. The articles in this focus issue range from overall perspective articles to research articles describing specific genomics applications for detection and control of diseases caused by nematode, viral, bacterial, fungal, and oomycete pathogens. The following are representative short summaries of the articles that appear in this Focus Issue .

Adaptive value of sex in microbial pathogens.

PubMed

Michod, Richard E; Bernstein, Harris; Nedelcu, Aurora M

2008-05-01

Explaining the adaptive value of sex is one of the great outstanding problems in biology. The challenge comes from the difficulty in identifying the benefits provided by sex, which must outweigh the substantial costs of sex. Here, we consider the adaptive value of sex in viruses, bacteria and fungi, and particularly the information available on the adaptive role of sex in pathogenic microorganisms. Our general theme is that the varied aspects of sex in pathogens illustrate the varied issues surrounding the evolution of sex generally. These include, the benefits of sex (in the short- and long-term), as well as the costs of sex (both to the host and to the pathogen). For the benefits of sex (that is, its adaptive value), we consider three hypotheses: (i) sex provides for effective and efficient recombinational repair of DNA damages, (ii) sex provides DNA for food, and (iii) sex produces variation and reduces genetic associations among alleles under selection. Although the evolution of sex in microbial pathogens illustrates these general issues, our paper is not a general review of theories for the evolution of sex in all organisms. Rather, we focus on the adaptive value of sex in microbial pathogens and conclude that in terms of short-term benefits, the DNA repair hypothesis has the most support and is the most generally applicable hypothesis in this group. In particular, recombinational repair of DNA damages may substantially benefit pathogens when challenged by the oxidative defenses of the host. However, in the long-term, sex may help get rid of mutations, increase the rate of adaptation of the population, and, in pathogens, may infrequently create new infective strains. An additional general issue about sex illustrated by pathogens is that some of the most interesting consequences of sex are not necessarily the reasons for which sex evolved. For example, antibiotic resistance may be transferred by bacterial sex, but this transfer is probably not the reason sex evolved in bacteria.

Rapid Waterborne Pathogen Detection with Mobile Electronics.

PubMed

Wu, Tsung-Feng; Chen, Yu-Chen; Wang, Wei-Chung; Kucknoor, Ashwini S; Lin, Che-Jen; Lo, Yu-Hwa; Yao, Chun-Wei; Lian, Ian

2017-06-09

Pathogen detection in water samples, without complex and time consuming procedures such as fluorescent-labeling or culture-based incubation, is essential to public safety. We propose an immunoagglutination-based protocol together with the microfluidic device to quantify pathogen levels directly from water samples. Utilizing ubiquitous complementary metal-oxide-semiconductor (CMOS) imagers from mobile electronics, a low-cost and one-step reaction detection protocol is developed to enable field detection for waterborne pathogens. 10 mL of pathogen-containing water samples was processed using the developed protocol including filtration enrichment, immune-reaction detection and imaging processing. The limit of detection of 10 E. coli O157:H7 cells/10 mL has been demonstrated within 10 min of turnaround time. The protocol can readily be integrated into a mobile electronics such as smartphones for rapid and reproducible field detection of waterborne pathogens.

Ecological disequilibrium drives insect pest and pathogen accumulation in non-native trees

PubMed Central

Burgess, Treena I.; Le Roux, Johannes J.; Richardson, David M.; Slippers, Bernard; Wingfield, Michael J.

2017-01-01

Abstract Non-native trees have become dominant components of many landscapes, including urban ecosystems, commercial forestry plantations, fruit orchards and as invasives in natural ecosystems. Often, these trees have been separated from their natural enemies (i.e. insects and pathogens) leading to ecological disequilibrium, that is, the immediate breakdown of historically co-evolved interactions once introduced into novel environments. Long-established, non-native tree plantations provide useful experiments to explore the dimensions of such ecological disequilibria. We quantify the status quo of non-native insect pests and pathogens catching up with their tree hosts (planted Acacia, Eucalyptus and Pinus species) in South Africa, and examine which native South African enemy species utilize these trees as hosts. Interestingly, pines, with no confamilial relatives in South Africa and the longest residence time (almost two centuries), have acquired only one highly polyphagous native pathogen. This is in contrast to acacias and eucalypts, both with many native and confamilial relatives in South Africa that have acquired more native pathogens. These patterns support the known role of phylogenetic relatedness of non-native and native floras in influencing the likelihood of pathogen shifts between them. This relationship, however, does not seem to hold for native insects. Native insects appear far more likely to expand their feeding habits onto non-native tree hosts than are native pathogens, although they are generally less damaging. The ecological disequilibrium conditions of non-native trees are deeply rooted in the eco-evolutionary experience of the host plant, co-evolved natural enemies and native organisms from the introduced range. We should expect considerable spatial and temporal variation in ecological disequilibrium conditions among non-native taxa, which can be significantly influenced by biosecurity and management practices. PMID:28013250

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

PubMed

Kim, Shin-Hee

2018-03-09

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

Mycobacterium abscessus phospholipase C expression is induced during coculture within amoebae and enhances M. abscessus virulence in mice.

PubMed

Bakala N'Goma, Jean Claude; Le Moigne, Vincent; Soismier, Nathalie; Laencina, Laura; Le Chevalier, Fabien; Roux, Anne-Laure; Poncin, Isabelle; Serveau-Avesque, Carole; Rottman, Martin; Gaillard, Jean-Louis; Etienne, Gilles; Brosch, Roland; Herrmann, Jean-Louis; Canaan, Stéphane; Girard-Misguich, Fabienne

2015-02-01

Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555, encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis. Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus. Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

PubMed Central

2018-01-01

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry. PMID:29522492

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification.

PubMed

Janse, Ingmar; Hamidjaja, Raditijo A; Bok, Jasper M; van Rotterdam, Bart J

2010-12-08

Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum.

Reliable detection of Bacillus anthracis, Francisella tularensis and Yersinia pestis by using multiplex qPCR including internal controls for nucleic acid extraction and amplification

PubMed Central

2010-01-01

Background Several pathogens could seriously affect public health if not recognized timely. To reduce the impact of such highly pathogenic micro-organisms, rapid and accurate diagnostic tools are needed for their detection in various samples, including environmental samples. Results Multiplex real-time PCRs were designed for rapid and reliable detection of three major pathogens that have the potential to cause high morbidity and mortality in humans: B. anthracis, F. tularensis and Y. pestis. The developed assays detect three pathogen-specific targets, including at least one chromosomal target, and one target from B. thuringiensis which is used as an internal control for nucleic acid extraction from refractory spores as well as successful DNA amplification. Validation of the PCRs showed a high analytical sensitivity, specificity and coverage of diverse pathogen strains. Conclusions The multiplex qPCR assays that were developed allow the rapid detection of 3 pathogen-specific targets simultaneously, without compromising sensitivity. The application of B. thuringiensis spores as internal controls further reduces false negative results. This ensures highly reliable detection, while template consumption and laboratory effort are kept at a minimum PMID:21143837

Multiplex PCR for simultaneous identification of E. coli O157:H7, Salmonella spp. and L. monocytogenes in food.

PubMed

Nguyen, Thuy Trang; Van Giau, Vo; Vo, Tuong Kha

2016-12-01

The rapid detection of pathogens in food is becoming increasingly critical for ensuring the safety of consumers, since the majority of food-borne illnesses and deaths are caused by pathogenic bacteria. Hence, rapid, sensitive, inexpensive and convenient approaches to detect food-borne pathogenic bacteria is essential in controlling food safety. In this study, a multiplex PCR assay for the rapid and simultaneous detection of Escherichia coli O157:H7, Salmonella spp. and Listeria monocytogenes was established. The invA, stx and hlyA genes specifically amplified DNA fragments of 284, 404 and 510 bp from Salmonella spp., L. monocytogenes and E. coli O157:H7, respectively. The 16S rRNA gene was targeted as an internal control gene in the presence of bacterial DNA. The specificity and sensitivity of the multiplex PCR were performed by testing different strains. The multiplex PCR assay was able to specifically simultaneously detect ten colony-forming unit/mL of each pathogen in artificially inoculated samples after enrichment for 12 h. The whole process took less than 24 h to complete, indicating that the assay is suitable for reliable and rapid identification of these three food-borne pathogens, which could be suitable in microbial epidemiology investigation.

Protein Chips for Detection of Salmonella spp. from Enrichment Culture

PubMed Central

Poltronieri, Palmiro; Cimaglia, Fabio; De Lorenzis, Enrico; Chiesa, Maurizio; Mezzolla, Valeria; Reca, Ida Barbara

2016-01-01

Food pathogens are the cause of foodborne epidemics, therefore there is a need to detect the pathogens in food productions rapidly. A pre-enrichment culture followed by selective agar plating are standard detection methods. Molecular methods such as qPCR have provided a first rapid protocol for detection of pathogens within 24 h of enrichment culture. Biosensors also may provide a rapid tool to individuate a source of Salmonella contamination at early times of pre-enrichment culture. Forty mL of Salmonella spp. enrichment culture were processed by immunoseparation using the Pathatrix, as in AFNOR validated qPCR protocols. The Salmonella biosensor combined with immunoseparation showed a limit of detection of 100 bacteria/40 mL, with a 400 fold increase to previous results. qPCR analysis requires processing of bead-bound bacteria with lysis buffer and DNA clean up, with a limit of detection of 2 cfu/50 μL. Finally, a protein chip was developed and tested in screening and identification of 5 common pathogen species, Salmonella spp., E. coli, S. aureus, Campylobacter spp. and Listeria spp. The protein chip, with high specificity in species identification, is proposed to be integrated into a Lab-on-Chip system, for rapid and reproducible screening of Salmonella spp. and other pathogen species contaminating food productions. PMID:27110786

A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus

PubMed Central

Korotkova, Ekaterina A.; Gmyl, Anatoly P.; Yakovenko, Maria L.; Ivanova, Olga E.; Eremeeva, Tatyana P.; Kozlovskaya, Liubov I.; Shakaryan, Armen K.; Lipskaya, Galina Y.; Parshina, Irina L.; Loginovskikh, Nataliya V.; Morozova, Nadezhda S.

2016-01-01

ABSTRACT Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. IMPORTANCE The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly diverged (Sabin-like) viruses on the one hand and those caused by significantly diverged VDPVs on the other. This classification is based on the number of mutations in the viral genome region encoding a viral structural protein. Until now, only sporadic poliomyelitis cases due to Sabin-like polioviruses had been described, and in distinction from the VDPV-triggered outbreaks, they did not require broad-scale epidemiological responses. Here, an unusual outbreak of poliomyelitis caused by a Sabin-like virus is reported, which had an exceptionally high disease/infection ratio. This outbreak blurred the borderline between Sabin-like polioviruses and VDPVs both in pathogenicity and in the kind of responses required, as well as underscoring important gaps in understanding the pathogenicity, epidemiology, and evolution of vaccine-derived polioviruses. PMID:27099315

A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus.

PubMed

Korotkova, Ekaterina A; Gmyl, Anatoly P; Yakovenko, Maria L; Ivanova, Olga E; Eremeeva, Tatyana P; Kozlovskaya, Liubov I; Shakaryan, Armen K; Lipskaya, Galina Y; Parshina, Irina L; Loginovskikh, Nataliya V; Morozova, Nadezhda S; Agol, Vadim I

2016-07-01

Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly diverged (Sabin-like) viruses on the one hand and those caused by significantly diverged VDPVs on the other. This classification is based on the number of mutations in the viral genome region encoding a viral structural protein. Until now, only sporadic poliomyelitis cases due to Sabin-like polioviruses had been described, and in distinction from the VDPV-triggered outbreaks, they did not require broad-scale epidemiological responses. Here, an unusual outbreak of poliomyelitis caused by a Sabin-like virus is reported, which had an exceptionally high disease/infection ratio. This outbreak blurred the borderline between Sabin-like polioviruses and VDPVs both in pathogenicity and in the kind of responses required, as well as underscoring important gaps in understanding the pathogenicity, epidemiology, and evolution of vaccine-derived polioviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans

PubMed Central

Moye, Zachary D.; Zeng, Lin; Burne, Robert A.

2014-01-01

The nature of the oral cavity and host behaviors has mandated that the oral microbiota evolve mechanisms for coping with environmental fluctuations, especially changes in the type and availability of carbohydrates. In the case of human dental caries, the presence of excess carbohydrates is often responsible for altering the local environment to be more favorable for species associated with the initiation and progression of disease, including Streptococcus mutans. Some of the earliest endeavors to understand how cariogenic species respond to environmental perturbations were carried out using chemostat cultivation, which provides fine control over culture conditions and bacterial behaviors. The development of genome-scale methodologies has allowed for the combination of sophisticated cultivation technologies with genome-level analysis to more thoroughly probe how bacterial pathogens respond to environmental stimuli. Recent investigations in S. mutans and other closely related streptococci have begun to reveal that carbohydrate metabolism can drastically impact pathogenic potential and highlight the important influence that nutrient acquisition has on the success of pathogens; inside and outside of the oral cavity. Collectively, research into pathogenic streptococci, which have evolved in close association with the human host, has begun to unveil the essential nature of careful orchestration of carbohydrate acquisition and catabolism to allow the organisms to persist and, when conditions allow, initiate or worsen disease. PMID:25317251

Sequestration and Scavenging of Iron in Infection

PubMed Central

Parrow, Nermi L.; Fleming, Robert E.

2013-01-01

The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen. PMID:23836822

'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution.

PubMed

McNally, Alan; Thomson, Nicholas R; Reuter, Sandra; Wren, Brendan W

2016-03-01

Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, and Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution. Finally, as these traits are also found in the genomes of other species in the Enterobacteriaceae, we suggest that they provide a blueprint for the evolution of enteropathogenic bacteria.

The Binding Interface between Human APOBEC3F and HIV-1 Vif Elucidated by Genetic and Computational Approaches.

PubMed

Richards, Christopher; Albin, John S; Demir, Özlem; Shaban, Nadine M; Luengas, Elizabeth M; Land, Allison M; Anderson, Brett D; Holten, John R; Anderson, John S; Harki, Daniel A; Amaro, Rommie E; Harris, Reuben S

2015-12-01

APOBEC3 family DNA cytosine deaminases provide overlapping defenses against pathogen infections. However, most viruses have elaborate evasion mechanisms such as the HIV-1 Vif protein, which subverts cellular CBF-β and a polyubiquitin ligase complex to neutralize these enzymes. Despite advances in APOBEC3 and Vif biology, a full understanding of this direct host-pathogen conflict has been elusive. We combine virus adaptation and computational studies to interrogate the APOBEC3F-Vif interface and build a robust structural model. A recurring compensatory amino acid substitution from adaptation experiments provided an initial docking constraint, and microsecond molecular dynamic simulations optimized interface contacts. Virus infectivity experiments validated a long-lasting electrostatic interaction between APOBEC3F E289 and HIV-1 Vif R15. Taken together with mutagenesis results, we propose a wobble model to explain how HIV-1 Vif has evolved to bind different APOBEC3 enzymes and, more generally, how pathogens may evolve to escape innate host defenses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity.

PubMed

Turula, Holly; Wobus, Christiane E

2018-05-03

The gastrointestinal tract houses millions of microbes, and thus has evolved several host defense mechanisms to keep them at bay, and prevent their entry into the host. One such mucosal surface defense is the secretion of secretory immunoglobulins (SIg). Secretion of SIg depends on the polymeric immunoglobulin receptor (pIgR), which transports polymeric Ig (IgA or IgM) from the basolateral surface of the epithelium to the apical side. Upon reaching the luminal side, a portion of pIgR, called secretory component (SC) is cleaved off to release Ig, forming SIg. Through antigen-specific and non-specific binding, SIg can modulate microbial communities and pathogenic microbes via several mechanisms: agglutination and exclusion from the epithelial surface, neutralization, or via host immunity and complement activation. Given the crucial role of SIg as a microbial scavenger, some pathogens also evolved ways to modulate and utilize pIgR and SIg to facilitate infection. This review will cover the regulation of the pIgR/SIg cycle, mechanisms of SIg-mediated mucosal protection as well as pathogen utilization of SIg.

Statistical Physics of T-Cell Development and Pathogen Specificity

NASA Astrophysics Data System (ADS)

Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

2013-04-01

In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

The trans-kingdom identification of negative regulators of pathogen hypervirulence

PubMed Central

Brown, Neil A.; Urban, Martin; Hammond-Kosack, Kim E.

2015-01-01

Modern society and global ecosystems are increasingly under threat from pathogens, which cause a plethora of human, animal, invertebrate and plant diseases. Of increasing concern is the trans-kingdom tendency for increased pathogen virulence that is beginning to emerge in natural, clinical and agricultural settings. The study of pathogenicity has revealed multiple examples of convergently evolved virulence mechanisms. Originally described as rare, but increasingly common, are interactions where a single gene deletion in a pathogenic species causes hypervirulence. This review utilised the pathogen–host interaction database (www.PHI-base.org) to identify 112 hypervirulent mutations from 37 pathogen species, and subsequently interrogates the trans-kingdom, conserved, molecular, biochemical and cellular themes that cause hypervirulence. This study investigates 22 animal and 15 plant pathogens including 17 bacterial and 17 fungal species. Finally, the evolutionary significance and trans-kingdom requirement for negative regulators of hypervirulence and the implication of pathogen hypervirulence and emerging infectious diseases on society are discussed. PMID:26468211

Probiotic therapy - recruiting old friends to fight new foes

PubMed Central

2010-01-01

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative. PMID:20579345

Rapid death of duck cells infected with influenza: a potential mechanism for host resistance to H5N1.

PubMed

Kuchipudi, Suresh V; Dunham, Stephen P; Nelli, Rahul; White, Gavin A; Coward, Vivien J; Slomka, Marek J; Brown, Ian H; Chang, Kin Chow

2012-01-01

Aquatic birds are the natural reservoir for most subtypes of influenza A, and a source of novel viruses with the potential to cause human pandemics, fatal zoonotic disease or devastating epizootics in poultry. It is well recognised that waterfowl typically show few clinical signs following influenza A infection, in contrast, terrestrial poultry such as chickens may develop severe disease with rapid death following infection with highly pathogenic avian influenza. This study examined the cellular response to influenza infection in primary cells derived from resistant (duck) and susceptible (chicken) avian hosts. Paradoxically, we observed that duck cells underwent rapid cell death following infection with low pathogenic avian H2N3, classical swine H1N1 and 'classical' highly pathogenic H5N1 viruses. Dying cells showed morphological features of apoptosis, increased DNA fragmentation and activation of caspase 3/7. Following infection of chicken cells, cell death occurred less rapidly, accompanied by reduced DNA fragmentation and caspase activation. Duck cells produced similar levels of viral RNA but less infectious virus, in comparison with chicken cells. Such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 fatal to ducks. The induction of rapid death in duck cells may be part of a mechanism of host resistance to influenza A, with the loss of this response leading to increased susceptibility to emergent strains of H5N1. These studies provide novel insights that should help resolve the long-standing enigma of host-pathogen relationships for highly pathogenic and zoonotic avian influenza.

Luciferase-Zinc-Finger System for the Rapid Detection of Pathogenic Bacteria.

PubMed

Shi, Chu; Xu, Qing; Ge, Yue; Jiang, Ling; Huang, He

2017-08-09

Rapid and reliable detection of pathogenic bacteria is crucial for food safety control. Here, we present a novel luciferase-zinc finger system for the detection of pathogens that offers rapid and specific profiling. The system, which uses a zinc-finger protein domain to probe zinc finger recognition sites, was designed to bind the amplified conserved regions of 16S rDNA, and the obtained products were detected using a modified luciferase. The luciferase-zinc finger system not only maintained luciferase activity but also allowed the specific detection of different bacterial species, with a sensitivity as low as 10 copies and a linear range from 10 to 10 4 copies per microliter of the specific PCR product. Moreover, the system is robust and rapid, enabling the simultaneous detection of 6 species of bacteria in artificially contaminated samples with excellent accuracy. Thus, we envision that our luciferase-zinc finger system will have far-reaching applications.

Label and label-free based surface-enhanced Raman scattering for pathogen bacteria detection: A review.

PubMed

Liu, Yu; Zhou, Haibo; Hu, Ziwei; Yu, Guangxia; Yang, Danting; Zhao, Jinshun

2017-08-15

Rapid, accurate detection of pathogen bacteria is a highly topical research area for the sake of food safety and public health. Surface-enhanced Raman scattering (SERS) is being considered as a powerful and attractive technique for pathogen bacteria detection, due to its sensitivity, high speed, comparatively low cost, multiplexing ability and portability. This contribution aims to give a comprehensive overview of SERS as a technique for rapid detection of pathogen bacteria based on label and label-free strategies. A brief tutorial on SERS is given first of all. Then we summarize the recent trends and developments of label and label-free based SERS applied to detection of pathogen bacteria, including the relatively complete interpretation of SERS spectra. In addition, multifunctional SERS platforms for pathogen bacteria in matrix are discussed as well. Furthermore, an outlook of the work done and a perspective on the future directions of SERS as a reliable tool for real-time pathogen bacteria detection are given. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward a better guard of coastal water safety-Microbial distribution in coastal water and their facile detection.

PubMed

Xie, Yunxuan; Qiu, Ning; Wang, Guangyi

2017-05-15

Prosperous development in marine-based tourism has raised increasing concerns over the sanitary quality of coastal waters with potential microbial contamination. The World Health Organization has set stringent standards over a list of pathogenic microorganisms posing potential threats to people with frequent coastal water exposure and has asked for efficient detection procedures for pathogen facile identification. Inspection of survey events regarding the occurrence of marine pathogens in recreational beaches in recent years has reinforced the need for the development of a rapid identification procedure. In this review, we examine the possibility of recruiting uniform molecular assays to identify different marine pathogens and the feasibility of appropriate biomarkers, including enterochelin biosynthetic genes, for general toxicity assays. The focus is not only on bacterial pathogens but also on other groups of infectious pathogens. The ultimate goal is the development of a handy method to more efficiently and rapidly detect marine pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Growth and survival of foodborne pathogens in beer.

PubMed

Menz, Garry; Aldred, Peter; Vriesekoop, Frank

2011-10-01

This work aimed to assess the growth and survival of four foodborne pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes, and Staphylococcus aureus) in beer. The effects of ethanol, pH, and storage temperature were investigated for the gram-negative pathogens (E. coli O157:H7 and Salmonella Typhimurium), whereas the presence of hops ensured that the gram-positive pathogens (L. monocytogenes and S. aureus) were rapidly inactivated in alcohol-free beer. The pathogens E. coli O157:H7 and Salmonella Typhimurium could not grow in the mid-strength or full-strength beers, although they could survive for more than 30 days in the mid-strength beer when held at 4°C. These pathogens grew rapidly in the alcohol-free beer; however, growth was prevented when the pH of the alcohol-free beer was lowered from the "as received" value of 4.3 to 4.0. Pathogen survival in all beers was prolonged at lowered storage temperatures.

Evolution of Bordetellae from Environmental Microbes to Human Respiratory Pathogens: Amoebae as a Missing Link.

PubMed

Taylor-Mulneix, Dawn L; Hamidou Soumana, Illiassou; Linz, Bodo; Harvill, Eric T

2017-01-01

The genus Bordetella comprises several bacterial species that colonize the respiratory tract of mammals. It includes B. pertussis , a human-restricted pathogen that is the causative agent of Whooping Cough. In contrast, the closely related species B. bronchiseptica colonizes a broad range of animals as well as immunocompromised humans. Recent metagenomic studies have identified known and novel bordetellae isolated from different environmental sources, providing a new perspective on their natural history. Using phylogenetic analysis, we have shown that human and animal pathogenic bordetellae have most likely evolved from ancestors that originated from soil and water. Our recent study found that B. bronchiseptica can evade amoebic predation and utilize Dictyostelium discoideum as an expansion and transmission vector, which suggests that the evolutionary pressure to evade the amoebic predator enabled the rise of bordetellae as respiratory pathogens. Interactions with amoeba may represent the starting point for bacterial adaptation to eukaryotic cells. However, as bacteria evolve and adapt to a novel host, they can become specialized and restricted to a specific host. B. pertussis is known to colonize and cause infection only in humans, and this specialization to a closed human-to-human lifecycle has involved genome reduction and the loss of ability to utilize amoeba as an environmental reservoir. The discoveries from studying the interaction of Bordetella species with amoeba will elicit a better understanding of the evolutionary history of these and other important human pathogens.

Inheritance of evolved resistance to a novel herbicide (pyroxasulfone).

PubMed

Busi, Roberto; Gaines, Todd A; Vila-Aiub, Martin M; Powles, Stephen B

2014-03-01

Agricultural weeds have rapidly adapted to intensive herbicide selection and resistance to herbicides has evolved within ecological timescales. Yet, the genetic basis of broad-spectrum generalist herbicide resistance is largely unknown. This study aims to determine the genetic control of non-target-site herbicide resistance trait(s) that rapidly evolved under recurrent selection of the novel lipid biosynthesis inhibitor pyroxasulfone in Lolium rigidum. The phenotypic segregation of pyroxasulfone resistance in parental, F1 and back-cross (BC) families was assessed in plants exposed to a gradient of pyroxasulfone doses. The inheritance of resistance to chemically dissimilar herbicides (cross-resistance) was also evaluated. Evolved resistance to the novel selective agent (pyroxasulfone) is explained by Mendelian segregation of one semi-dominant allele incrementally herbicide-selected at higher frequency in the progeny. In BC families, cross-resistance is conferred by an incompletely dominant single major locus. This study confirms that herbicide resistance can rapidly evolve to any novel selective herbicide agents by continuous and repeated herbicide use. The results imply that the combination of herbicide options (rotation, mixtures or combinations) to exploit incomplete dominance can provide acceptable control of broad-spectrum generalist resistance-endowing monogenic traits. Herbicide diversity within a set of integrated management tactics can be one important component to reduce the herbicide selection intensity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Microfluidic devices for sample preparation and rapid detection of foodborne pathogens.

PubMed

Kant, Krishna; Shahbazi, Mohammad-Ali; Dave, Vivek Priy; Ngo, Tien Anh; Chidambara, Vinayaka Aaydha; Than, Linh Quyen; Bang, Dang Duong; Wolff, Anders

2018-03-10

Rapid detection of foodborne pathogens at an early stage is imperative for preventing the outbreak of foodborne diseases, known as serious threats to human health. Conventional bacterial culturing methods for foodborne pathogen detection are time consuming, laborious, and with poor pathogen diagnosis competences. This has prompted researchers to call the current status of detection approaches into question and leverage new technologies for superior pathogen sensing outcomes. Novel strategies mainly rely on incorporating all the steps from sample preparation to detection in miniaturized devices for online monitoring of pathogens with high accuracy and sensitivity in a time-saving and cost effective manner. Lab on chip is a blooming area in diagnosis, which exploits different mechanical and biological techniques to detect very low concentrations of pathogens in food samples. This is achieved through streamlining the sample handling and concentrating procedures, which will subsequently reduce human errors and enhance the accuracy of the sensing methods. Integration of sample preparation techniques into these devices can effectively minimize the impact of complex food matrix on pathogen diagnosis and improve the limit of detections. Integration of pathogen capturing bio-receptors on microfluidic devices is a crucial step, which can facilitate recognition abilities in harsh chemical and physical conditions, offering a great commercial benefit to the food-manufacturing sector. This article reviews recent advances in current state-of-the-art of sample preparation and concentration from food matrices with focus on bacterial capturing methods and sensing technologies, along with their advantages and limitations when integrated into microfluidic devices for online rapid detection of pathogens in foods and food production line. Copyright © 2018. Published by Elsevier Inc.

Variable virulence among isolates of Ascosphaera apis: testing the parasite-pathogen hypothesis for the evolution of polyandry in social insects

NASA Astrophysics Data System (ADS)

Lee, G. M.; McGee, P. A.; Oldroyd, B. P.

2013-03-01

The queens of many eusocial insect species are polyandrous. The evolution of polyandry from ancestral monoandry is intriguing because polyandry undermines the kin-selected benefits of high intracolonial relatedness that are understood to have been central to the evolution of eusociality. An accumulating body of evidence suggests that polyandry evolved from monoandry in part because genetically diverse colonies better resist infection by pathogens. However, a core assumption of the "parasite-pathogen hypothesis", that there is variation in virulence among strains of pathogens, remains largely untested in vivo. Here, we demonstrate variation in virulence among isolates of Ascosphaera apis, the causative organism of chalkbrood disease in its honey bee ( Apis mellifera) host. More importantly, we show a pathogen-host genotypic interaction for resistance and pathogenicity. Our findings therefore support the parasite-parasite hypothesis as a factor in the evolution of polyandry among eusocial insects.

Genome plasticity in filamentous plant pathogens contributes to the emergence of novel effectors and their cellular processes in the host.

PubMed

Dong, Yanhan; Li, Ying; Qi, Zhongqiang; Zheng, Xiaobo; Zhang, Zhengguang

2016-02-01

Plant diseases cause extensive yield loss of crops worldwide, and secretory 'warfare' occurs between plants and pathogenic organisms all the time. Filamentous plant pathogens have evolved the ability to manipulate host processes and facilitate colonization through secreting effectors inside plant cells. The stresses from hosts and environment can drive the genome dynamics of plant pathogens. Remarkable advances in plant pathology have been made owing to these adaptable genome regions of several lineages of filamentous phytopathogens. Characterization new effectors and interaction analyses between pathogens and plants have provided molecular insights into the plant pathways perturbed during the infection process. In this mini-review, we highlight promising approaches of identifying novel effectors based on the genome plasticity. We also discuss the interaction mechanisms between plants and their filamentous pathogens and outline the possibilities of effector gene expression under epigenetic control that will be future directions for research.

Detection and characterization of foodborne pathogenic bacteria with hyperspectral microscope imaging

USDA-ARS?s Scientific Manuscript database

Rapid detection and identification of pathogenic microorganisms naturally occurring during food processing are important in developing intervention and verification strategies. In the poultry industry, contamination of poultry meat with foodborne pathogens (especially, Salmonella and Campylobacter) ...

A rapid method for the detection of foodborne pathogens by extraction of a trace amount of DNA from raw milk based on amino-modified silica-coated magnetic nanoparticles and polymerase chain reaction.

PubMed

Bai, Yalong; Song, Minghui; Cui, Yan; Shi, Chunlei; Wang, Dapeng; Paoli, George C; Shi, Xianming

2013-07-17

A method based on amino-modified silica-coated magnetic nanoparticles (ASMNPs) and polymerase chain reaction (PCR) was developed to rapidly and sensitively detect foodborne pathogens in raw milk. After optimizing parameters such as pH, temperature, and time, a trace amount of genomic DNA of pathogens could be extracted directly from complex matrices such as raw milk using ASMNPs. The magnetically separated complexes of genomic DNA and ASMNPs were directly subjected to single PCR (S-PCR) or multiplex PCR (M-PCR) to detect single or multiple pathogens from raw milk samples. Salmonella Enteritidis (Gram-negative) and Listeria monocytogenes (Gram-positive) were used as model organisms to artificially contaminate raw milk samples. After magnetic separation and S-PCR, the detection sensitivities were 8 CFU mL(-1) and 13 CFU mL(-1) respectively for these two types of pathogens. Furthermore, this method was successfully used to detect multiple pathogens (S. Enteritidis and L. monocytogenes) from artificially contaminated raw milk using M-PCR at sensitivities of 15 CFU mL(-1) and 25 CFU mL(-1), respectively. This method has great potential to rapidly and sensitively detect pathogens in raw milk or other complex food matrices. Copyright © 2013 Elsevier B.V. All rights reserved.

Evidence for a high mutation rate at rapidly evolving yeast centromeres.

PubMed

Bensasson, Douda

2011-07-18

Although their role in cell division is essential, centromeres evolve rapidly in animals, plants and yeasts. Unlike the complex centromeres of plants and aminals, the point centromeres of Saccharomcyes yeasts can be readily sequenced to distinguish amongst the possible explanations for fast centromere evolution. Using DNA sequences of all 16 centromeres from 34 strains of Saccharomyces cerevisiae and population genomic data from Saccharomyces paradoxus, I show that centromeres in both species evolve 3 times more rapidly even than selectively unconstrained DNA. Exceptionally high levels of polymorphism seen in multiple yeast populations suggest that rapid centromere evolution does not result from the repeated selective sweeps expected under meiotic drive. I further show that there is little evidence for crossing-over or gene conversion within centromeres, although there is clear evidence for recombination in their immediate vicinity. Finally I show that the mutation spectrum at centromeres is consistent with the pattern of spontaneous mutation elsewhere in the genome. These results indicate that rapid centromere evolution is a common phenomenon in yeast species. Furthermore, these results suggest that rapid centromere evolution does not result from the mutagenic effect of gene conversion, but from a generalised increase in the mutation rate, perhaps arising from the unusual chromatin structure at centromeres in yeast and other eukaryotes.

Evidence for a high mutation rate at rapidly evolving yeast centromeres

PubMed Central

2011-01-01

Background Although their role in cell division is essential, centromeres evolve rapidly in animals, plants and yeasts. Unlike the complex centromeres of plants and aminals, the point centromeres of Saccharomcyes yeasts can be readily sequenced to distinguish amongst the possible explanations for fast centromere evolution. Results Using DNA sequences of all 16 centromeres from 34 strains of Saccharomyces cerevisiae and population genomic data from Saccharomyces paradoxus, I show that centromeres in both species evolve 3 times more rapidly even than selectively unconstrained DNA. Exceptionally high levels of polymorphism seen in multiple yeast populations suggest that rapid centromere evolution does not result from the repeated selective sweeps expected under meiotic drive. I further show that there is little evidence for crossing-over or gene conversion within centromeres, although there is clear evidence for recombination in their immediate vicinity. Finally I show that the mutation spectrum at centromeres is consistent with the pattern of spontaneous mutation elsewhere in the genome. Conclusions These results indicate that rapid centromere evolution is a common phenomenon in yeast species. Furthermore, these results suggest that rapid centromere evolution does not result from the mutagenic effect of gene conversion, but from a generalised increase in the mutation rate, perhaps arising from the unusual chromatin structure at centromeres in yeast and other eukaryotes. PMID:21767380

Method for genetic identification of unknown organisms

DOEpatents

Colston, Jr., Billy W.; Fitch, Joseph P.; Hindson, Benjamin J.; Carter, Chance J.; Beer, Neil Reginald

2016-08-23

A method of rapid, genome and proteome based identification of unknown pathogenic or non-pathogenic organisms in a complex sample. The entire sample is analyzed by creating millions of emulsion encapsulated microdroplets, each containing a single pathogenic or non-pathogenic organism sized particle and appropriate reagents for amplification. Following amplification, the amplified product is analyzed.

Engineered nanoconstructs for the multiplexed and sensitive detection of high-risk pathogens

NASA Astrophysics Data System (ADS)

Seo, Youngmin; Kim, Ji-Eun; Jeong, Yoon; Lee, Kwan Hong; Hwang, Jangsun; Hong, Jongwook; Park, Hansoo; Choi, Jonghoon

2016-01-01

Many countries categorize the causative agents of severe infectious diseases as high-risk pathogens. Given their extreme infectivity and potential to be used as biological weapons, a rapid and sensitive method for detection of high-risk pathogens (e.g., Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Vaccinia virus) is highly desirable. Here, we report the construction of a novel detection platform comprising two units: (1) magnetic beads separately conjugated with multiple capturing antibodies against four different high-risk pathogens for simple and rapid isolation, and (2) genetically engineered apoferritin nanoparticles conjugated with multiple quantum dots and detection antibodies against four different high-risk pathogens for signal amplification. For each high-risk pathogen, we demonstrated at least 10-fold increase in sensitivity compared to traditional lateral flow devices that utilize enzyme-based detection methods. Multiplexed detection of high-risk pathogens in a sample was also successful by using the nanoconstructs harboring the dye molecules with fluorescence at different wavelengths. We ultimately envision the use of this novel nanoprobe detection platform in future applications that require highly sensitive on-site detection of high-risk pathogens.

Comparative Pathogenomics Reveals Horizontally Acquired Novel Virulence Genes in Fungi Infecting Cereal Hosts

PubMed Central

Gardiner, Donald M.; McDonald, Megan C.; Covarelli, Lorenzo; Solomon, Peter S.; Rusu, Anca G.; Marshall, Mhairi; Kazan, Kemal; Chakraborty, Sukumar; McDonald, Bruce A.; Manners, John M.

2012-01-01

Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens. PMID:23028337

Adaptive evolution of centromere proteins in plants and animals.

PubMed

Talbert, Paul B; Bryson, Terri D; Henikoff, Steven

2004-01-01

Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences that are rapidly evolving. The nucleosomes of centromeres are characterized by a special H3-like histone (CenH3), which evolves rapidly and adaptively in Drosophila and Arabidopsis. Most plant, animal and fungal centromeres also bind a large protein, centromere protein C (CENP-C), that is characterized by a single 24 amino-acid motif (CENPC motif). Whereas we find no evidence that mammalian CenH3 (CENP-A) has been evolving adaptively, mammalian CENP-C proteins contain adaptively evolving regions that overlap with regions of DNA-binding activity. In plants we find that CENP-C proteins have complex duplicated regions, with conserved amino and carboxyl termini that are dissimilar in sequence to their counterparts in animals and fungi. Comparisons of Cenpc genes from Arabidopsis species and from grasses revealed multiple regions that are under positive selection, including duplicated exons in some grasses. In contrast to plants and animals, yeast CENP-C (Mif2p) is under negative selection. CENP-Cs in all plant and animal lineages examined have regions that are rapidly and adaptively evolving. To explain these remarkable evolutionary features for a single-copy gene that is needed at every mitosis, we propose that CENP-Cs, like some CenH3s, suppress meiotic drive of centromeres during female meiosis. This process can account for the rapid evolution and the complexity of centromeric DNA in plants and animals as compared to fungi.

Adaptive evolution of centromere proteins in plants and animals

PubMed Central

Talbert, Paul B; Bryson, Terri D; Henikoff, Steven

2004-01-01

Background Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences that are rapidly evolving. The nucleosomes of centromeres are characterized by a special H3-like histone (CenH3), which evolves rapidly and adaptively in Drosophila and Arabidopsis. Most plant, animal and fungal centromeres also bind a large protein, centromere protein C (CENP-C), that is characterized by a single 24 amino-acid motif (CENPC motif). Results Whereas we find no evidence that mammalian CenH3 (CENP-A) has been evolving adaptively, mammalian CENP-C proteins contain adaptively evolving regions that overlap with regions of DNA-binding activity. In plants we find that CENP-C proteins have complex duplicated regions, with conserved amino and carboxyl termini that are dissimilar in sequence to their counterparts in animals and fungi. Comparisons of Cenpc genes from Arabidopsis species and from grasses revealed multiple regions that are under positive selection, including duplicated exons in some grasses. In contrast to plants and animals, yeast CENP-C (Mif2p) is under negative selection. Conclusions CENP-Cs in all plant and animal lineages examined have regions that are rapidly and adaptively evolving. To explain these remarkable evolutionary features for a single-copy gene that is needed at every mitosis, we propose that CENP-Cs, like some CenH3s, suppress meiotic drive of centromeres during female meiosis. This process can account for the rapid evolution and the complexity of centromeric DNA in plants and animals as compared to fungi. PMID:15345035

Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse.

PubMed

Choi, Won-Suk; Baek, Yun Hee; Kwon, Jin Jung; Jeong, Ju Hwan; Park, Su-Jin; Kim, Young-Il; Yoon, Sun-Woo; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J; Choi, Young Ki; Song, Min-Suk

2017-01-17

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD 50 , up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential.

Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse

PubMed Central

Choi, Won-Suk; Baek, Yun Hee; Kwon, Jin Jung; Jeong, Ju Hwan; Park, Su-Jin; Kim, Young-il; Yoon, Sun-Woo; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J.; Choi, Young Ki; Song, Min-Suk

2017-01-01

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential. PMID:28094780

Genome Sequencing and Comparative Transcriptomics of the Model Entomopathogenic Fungi Metarhizium anisopliae and M. acridum

PubMed Central

Shang, Yanfang; Duan, Zhibing; Hu, Xiao; Xie, Xue-Qin; Zhou, Gang; Peng, Guoxiong; Luo, Zhibing; Huang, Wei; Wang, Bing; Fang, Weiguo; Wang, Sibao; Zhong, Yi; Ma, Li-Jun; St. Leger, Raymond J.; Zhao, Guo-Ping; Pei, Yan; Feng, Ming-Guang; Xia, Yuxian; Wang, Chengshu

2011-01-01

Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ∼30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ∼16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogenous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties. PMID:21253567

Achieving sustainable plant disease management through evolutionary principles.

PubMed

Zhan, Jiasui; Thrall, Peter H; Burdon, Jeremy J

2014-09-01

Plants and their pathogens are engaged in continuous evolutionary battles and sustainable disease management requires novel systems to create environments conducive for short-term and long-term disease control. In this opinion article, we argue that knowledge of the fundamental factors that drive host-pathogen coevolution in wild systems can provide new insights into disease development in agriculture. Such evolutionary principles can be used to guide the formulation of sustainable disease management strategies which can minimize disease epidemics while simultaneously reducing pressure on pathogens to evolve increased infectivity and aggressiveness. To ensure agricultural sustainability, disease management programs that reflect the dynamism of pathogen population structure are essential and evolutionary biologists should play an increasing role in their design. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

PubMed Central

Kimmey, Jacqueline M.; Stallings, Christina L.

2016-01-01

Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis. In light of current efforts to manipulate autophagy and the development of host-directed therapies to fight bacterial infections, we also discuss the implications stemming from the complicated relationship that exists between autophagy and bacterial pathogens. PMID:27866924

Mechanisms of innate immune evasion in re-emerging RNA viruses.

PubMed

Ma, Daphne Y; Suthar, Mehul S

2015-06-01

Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and other emerging/re-emerging RNA viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. As part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication, limit virus spread and activate adaptive immune responses. Concordantly, viral pathogens have evolved several strategies to counteract pathogen recognition and cell-intrinsic antiviral responses. In this review, we highlight the major mechanisms of innate immune evasion by emerging and re-emerging RNA viruses, focusing on pathogens that pose significant risk to public health. Copyright © 2015 Elsevier B.V. All rights reserved.

Host-pathogen interaction in Fusarium oxysporum infections: where do we stand?

PubMed

Husaini, Amjad M; Sakina, Aafreen; Cambay, Souliha R

2018-03-16

Fusarium oxysporum, a ubiquitous soil-borne pathogen causes devastating vascular wilt in more than 100 plant species and ranks fifth among top ten fungal plant pathogens. It has emerged as a human pathogen too, causing infections in immune-compromised patients. It is, therefore, important to gain insight into the molecular processes involved in the pathogenesis of this trans-kingdom pathogen. A complex network comprising of interconnected and over lapping signal pathways; mitogen-activated protein kinase (MAPK) signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex and cAMP pathways, is involved in perceiving the host. This network regulates the expression of various pathogenicity genes. Plants have however evolved an elaborate protection system to combat this attack. They too possess intricate mechanisms at molecular level, which once triggered by pathogen attack transduce signals to activate defense response. This review focuses on understanding and presenting a wholistic picture of the molecular mechanisms of F. oxysporum-host interactions in plant immunity.

Controlling hormone signaling is a plant and pathogen challenge for growth and survival.

PubMed

López, Miguel Angel; Bannenberg, Gerard; Castresana, Carmen

2008-08-01

Plants and pathogens have continuously confronted each other during evolution in a battle for growth and survival. New advances in the field have provided fascinating insights into the mechanisms that have co-evolved to gain a competitive advantage in this battle. When plants encounter an invading pathogen, not only responses signaled by defense hormones are activated to restrict pathogen invasion, but also the modulation of additional hormone pathways is required to serve other purposes, which are equally important for plant survival, such as re-allocation of resources, control of cell death, regulation of water stress, and modification of plant architecture. Notably, pathogens can counteract both types of responses as a strategy to enhance virulence. Pathogens regulate production and signaling responses of plant hormones during infection, and also produce phytohormones themselves to modulate plant responses. These results indicate that hormone signaling is a relevant component in plant-pathogen interactions, and that the ability to dictate hormonal directionality is critical to the outcome of an interaction.

Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

PubMed

Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

2015-06-01

Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interdigitated microelectrode based impedance biosensor for detection of salmonella enteritidis in food samples

NASA Astrophysics Data System (ADS)

Kim, G.; Morgan, M.; Hahm, B. K.; Bhunia, A.; Mun, J. H.; Om, A. S.

2008-03-01

Salmonella enteritidis outbreaks continue to occur, and S. enteritidis-related outbreaks from various food sources have increased public awareness of this pathogen. Conventional methods for pathogens detection and identification are labor-intensive and take days to complete. Some immunological rapid assays are developed, but these assays still require prolonged enrichment steps. Recently developed biosensors have shown great potential for the rapid detection of foodborne pathogens. To develop the biosensor, an interdigitated microelectrode (IME) was fabricated by using semiconductor fabrication process. Anti-Salmonella antibodies were immobilized based on avidin-biotin binding on the surface of the IME to form an active sensing layer. To increase the sensitivity of the sensor, three types of sensors that have different electrode gap sizes (2 μm, 5 μm, 10 μm) were fabricated and tested. The impedimetric biosensor could detect 103 CFU/mL of Salmonella in pork meat extract with an incubation time of 5 minutes. This method may provide a simple, rapid and sensitive method to detect foodborne pathogens.

Electrochemical Biosensor for Rapid and Sensitive Detection of Magnetically Extracted Bacterial Pathogens

PubMed Central

Setterington, Emma B.; Alocilja, Evangelyn C.

2012-01-01

Biological defense and security applications demand rapid, sensitive detection of bacterial pathogens. This work presents a novel qualitative electrochemical detection technique which is applied to two representative bacterial pathogens, Bacillus cereus (as a surrogate for B. anthracis) and Escherichia coli O157:H7, resulting in detection limits of 40 CFU/mL and 6 CFU/mL, respectively, from pure culture. Cyclic voltammetry is combined with immunomagnetic separation in a rapid method requiring approximately 1 h for presumptive positive/negative results. An immunofunctionalized magnetic/polyaniline core/shell nano-particle (c/sNP) is employed to extract target cells from the sample solution and magnetically position them on a screen-printed carbon electrode (SPCE) sensor. The presence of target cells significantly inhibits current flow between the electrically active c/sNPs and SPCE. This method has the potential to be adapted for a wide variety of target organisms and sample matrices, and to become a fully portable system for routine monitoring or emergency detection of bacterial pathogens. PMID:25585629

[Microbiology--laboratory examinations for bacterias].

PubMed

Hen, Renjun; Imafuku, Yuji; Yoshida, Hiroshi

2002-11-01

As it has been required to identify pathogenic microbes in shorter times, simple and rapid methods have been developed and used. Here, we summarized the present situation of rapid diagnostic testing in clinical microbiology in Japan, and also presented our results on PBP2' detection. The rapid test kits available in Japan for E. coli, Helicobacter pylori, Salmonella, Streptococcus and Staphylococcus aureus were described. Rapid examination methods are based mainly on immunologic reactions, which included slide agglutination using latex particle, immunochromatography and ELISA. Times required for the identification are 10 to 15 minutes. Moreover, rapid test kits employing PCR are also marketed. Further, we evaluated MRSA-LA "Seiken" which is a rapid detection kit for PBP2' produced by MRSA. The test was shown to be highly sensitive and specific. For the rapid identification of pathogenic microbes, simple and rapid test kits described here will be used more in clinical diagnosis.

Real-time and rapid detection of Salmonella Typhimurium using an inexpensive lab-built surface plasmon resonance setup

NASA Astrophysics Data System (ADS)

Lukose, Jijo; Shetty, Vignesh; Ballal, Mamatha; Chidangil, Santhosh; Sinha, Rajeev K.

2018-07-01

Cost-effective diagnostic platforms for rapid pathogen detection are always incumbent in both developing and developed worlds. However, exorbitant diagnostic expenses and the inability to detect pathogens early are a matter of concern for the sustainability and affordability of healthcare devices, which are crucial for deciding how to provide healthcare solutions to the masses, especially in developing countries. Herein, we present the rapid and real-time detection of Salmonella Typhimurium using an inexpensive lab-built surface plasmon resonance (SPR) imaging set up. Pathogen detection is accomplished with the aid of a monoclonal antibody immobilized on a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide): N-hydroxysuccinimide-modified self-assembled monolayer covalently bonded to a Au thin film. Successful pathogen detection is performed at two concentrations, ~1.5  ×  108 and ~1  ×  106 cfu ml‑1, in phosphate-buffered saline solution. The developed system is capable of detecting bacterial cells within 6–7 min after their injection into the SPR sensor surface. The present study reveals a cost-effective device having high potential for pathogen detection without any labelling tags.

Novel H5N8 clade 2.3.4.4 highly pathogenic avian influenza virus in wild awuatic birds, Russia, 2016

USDA-ARS?s Scientific Manuscript database

H5N1 high pathogenicity avian influenza virus (HPAIV) emerged in 1996 in Guangdong China (Gs/GD) and has evolved into multiple genetic clades. Since 2008, HPAIV H5 clade 2.3.4 with N2, N5 and N8 neuraminidase subtypes have been identified in mainland China and outbreak of HPAIV H5N8 clade 2.3.4.4 ou...

LAMP detection assays for boxwood blight pathogens: a comparative genomics approach

USDA-ARS?s Scientific Manuscript database

Rapid and accurate molecular diagnostic tools are critical to efforts to minimize the impact and spread of emergent pathogens. The identification of diagnostic markers for novel pathogens presents several challenges, especially in the absence of information about population diversity, and where gen...

Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans

PubMed Central

Schountz, Tony; Baker, Michelle L.; Butler, John; Munster, Vincent

2017-01-01

Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology. PMID:28959255

Reconstruction of an SSR-based Magnaporthe oryzae physical map to locate avirulence gene AvrPi12.

PubMed

Li, Tonghui; Wen, Jianqiang; Zhang, Yaling; Correll, James; Wang, Ling; Pan, Qinghua

2018-05-31

Pathogen avirulence (Avr) genes can evolve rapidly when challenged by the widespread deployment of host genes for resistance. They can be effectively isolated by positional cloning provided a robust and well-populated genetic map is available. An updated, SSR-based physical map of the rice blast pathogen Magnaporthe oryzae (Mo) has been constructed based on 116 of the 120 SSRs used to assemble the last map, along with 18 newly developed ones. A comparison between the two versions of the map has revealed an altered marker content and order within most of the Mo chromosomes. The avirulence gene AvrPi12 was mapped in a population of 219 progeny derived from a cross between the two Mo isolates CHL42 and CHL357. A bulked segregant analysis indicated that the gene was located on chromosome 6, a conclusion borne out by an analysis of the pattern of segregation shown by individual isolates. Six additional PCR-based markers were developed to improve the map resolution in the key region. AvrPi12 was finally located within the sub-telomeric region of chromosome 6, distal to the SSR locus LSM6-5. The improved SSR-based linkage map should be useful as a platform for gene mapping and isolation in Mo. It was used to establish the location of AvrPi12, thereby providing a starting point for its positional cloning.

Light acclimation, retrograde signalling, cell death and immune defences in plants.

PubMed

Karpiński, Stanisław; Szechyńska-Hebda, Magdalena; Wituszyńska, Weronika; Burdiak, Paweł

2013-04-01

This review confronts the classical view of plant immune defence and light acclimation with recently published data. Earlier findings have linked plant immune defences to nucleotide-binding site leucine-rich repeat (NBS-LRR)-dependent recognition of pathogen effectors and to the role of plasma membrane-localized NADPH-dependent oxidoreductase (AtRbohD), reactive oxygen species (ROS) and salicylic acid (SA). However, recent results suggest that plant immune defence also depends on the absorption of excessive light energy and photorespiration. Rapid changes in light intensity and quality often cause the absorption of energy, which is in excess of that required for photosynthesis. Such excessive light energy is considered to be a factor triggering photoinhibition and disturbance in ROS/hormonal homeostasis, which leads to cell death in foliar tissues. We highlight here the tight crosstalk between ROS- and SA-dependent pathways leading to light acclimation, and defence responses leading to pathogen resistance. We also show that LESION SIMULATING DISEASE 1 (LSD1) regulates and integrates these processes. Moreover, we discuss the role of plastid-nucleus signal transduction, photorespiration, photoelectrochemical signalling and 'light memory' in the regulation of acclimation and immune defence responses. All of these results suggest that plants have evolved a genetic system that simultaneously regulates systemic acquired resistance (SAR), cell death and systemic acquired acclimation (SAA). © 2012 Blackwell Publishing Ltd.

Genomic mechanisms accounting for the adaptation to parasitism in nematode-trapping fungi.

PubMed

Meerupati, Tejashwari; Andersson, Karl-Magnus; Friman, Eva; Kumar, Dharmendra; Tunlid, Anders; Ahrén, Dag

2013-11-01

Orbiliomycetes is one of the earliest diverging branches of the filamentous ascomycetes. The class contains nematode-trapping fungi that form unique infection structures, called traps, to capture and kill free-living nematodes. The traps have evolved differently along several lineages and include adhesive traps (knobs, nets or branches) and constricting rings. We show, by genome sequencing of the knob-forming species Monacrosporium haptotylum and comparison with the net-forming species Arthrobotrys oligospora, that two genomic mechanisms are likely to have been important for the adaptation to parasitism in these fungi. Firstly, the expansion of protein domain families and the large number of species-specific genes indicated that gene duplication followed by functional diversification had a major role in the evolution of the nematode-trapping fungi. Gene expression indicated that many of these genes are important for pathogenicity. Secondly, gene expression of orthologs between the two fungi during infection indicated that differential regulation was an important mechanism for the evolution of parasitism in nematode-trapping fungi. Many of the highly expressed and highly upregulated M. haptotylum transcripts during the early stages of nematode infection were species-specific and encoded small secreted proteins (SSPs) that were affected by repeat-induced point mutations (RIP). An active RIP mechanism was revealed by lack of repeats, dinucleotide bias in repeats and genes, low proportion of recent gene duplicates, and reduction of recent gene family expansions. The high expression and rapid divergence of SSPs indicate a striking similarity in the infection mechanisms of nematode-trapping fungi and plant and insect pathogens from the crown groups of the filamentous ascomycetes (Pezizomycotina). The patterns of gene family expansions in the nematode-trapping fungi were more similar to plant pathogens than to insect and animal pathogens. The observation of RIP activity in the Orbiliomycetes suggested that this mechanism was present early in the evolution of the filamentous ascomycetes.

Genomic Mechanisms Accounting for the Adaptation to Parasitism in Nematode-Trapping Fungi

PubMed Central

Meerupati, Tejashwari; Andersson, Karl-Magnus; Friman, Eva; Kumar, Dharmendra; Tunlid, Anders; Ahrén, Dag

2013-01-01

Orbiliomycetes is one of the earliest diverging branches of the filamentous ascomycetes. The class contains nematode-trapping fungi that form unique infection structures, called traps, to capture and kill free-living nematodes. The traps have evolved differently along several lineages and include adhesive traps (knobs, nets or branches) and constricting rings. We show, by genome sequencing of the knob-forming species Monacrosporium haptotylum and comparison with the net-forming species Arthrobotrys oligospora, that two genomic mechanisms are likely to have been important for the adaptation to parasitism in these fungi. Firstly, the expansion of protein domain families and the large number of species-specific genes indicated that gene duplication followed by functional diversification had a major role in the evolution of the nematode-trapping fungi. Gene expression indicated that many of these genes are important for pathogenicity. Secondly, gene expression of orthologs between the two fungi during infection indicated that differential regulation was an important mechanism for the evolution of parasitism in nematode-trapping fungi. Many of the highly expressed and highly upregulated M. haptotylum transcripts during the early stages of nematode infection were species-specific and encoded small secreted proteins (SSPs) that were affected by repeat-induced point mutations (RIP). An active RIP mechanism was revealed by lack of repeats, dinucleotide bias in repeats and genes, low proportion of recent gene duplicates, and reduction of recent gene family expansions. The high expression and rapid divergence of SSPs indicate a striking similarity in the infection mechanisms of nematode-trapping fungi and plant and insect pathogens from the crown groups of the filamentous ascomycetes (Pezizomycotina). The patterns of gene family expansions in the nematode-trapping fungi were more similar to plant pathogens than to insect and animal pathogens. The observation of RIP activity in the Orbiliomycetes suggested that this mechanism was present early in the evolution of the filamentous ascomycetes. PMID:24244185

Development of a rapid and simple Agrobacterium tumefaciens mediated transformation system for the fungal pathogen Heterobasidion annosum

Treesearch

Nicklas Samils; Malin Elfstrand; Daniel L. Lindner Czederpiltz; Jan Fahleson; Ake Olson; Christina Dixelius; Jan Stenlid

2006-01-01

Heterobasidion annosum causes root and butt-rot in trees and is the most serious forest pathogen in the northern hemisphere. We developed a rapid and simple Agrobacterium-mediated method of gene delivery into H. annosum to be used in functional studies of candidate genes and for visualization of mycelial interactions. Heterobasidion annosum TC 32-1 was cocultivated at...

Molecular characterization of avian influenza H5N1 virus in Egypt and the emergence of a novel endemic subclade

PubMed Central

El-Shesheny, Rabeh; Kandeil, Ahmed; Bagato, Ola; Maatouq, Asmaa M.; Moatasim, Yassmin; Rubrum, Adam; Song, Min-Suk; Webby, Richard J.

2014-01-01

Clade 2.2 highly pathogenic H5N1 viruses have been in continuous circulation in Egyptian poultry since 2006. Their persistence caused significant genetic drift that led to the reclassification of these viruses into subclades 2.2.1 and 2.2.1.1. Here, we conducted full-genome sequence and phylogenetic analyses of 45 H5N1 isolated during 2006–2013 through systematic surveillance in Egypt, and 53 viruses that were sequenced previously and available in the public domain. Results indicated that H5N1 viruses in Egypt continue to evolve and a new distinct cluster has emerged. Mutations affecting viral virulence, pathogenicity, transmission, receptor-binding preference and drug resistance were studied. In light of our findings that H5N1 in Egypt continues to evolve, surveillance and molecular studies need to be sustained. PMID:24722680

Reprogramming the virulence: Insect defense molecules navigating the epigenetic landscape of Metarhizium robertsii.

PubMed

Hussain, Abid

2018-01-01

Metarhizium species are the leading bio-control agents well characterized regarding pathogenicity to agricultural, forest, public health, stored grains and urban insect pests. They infect the target host through the tight conidial adherence with the insect cuticle. Conidial binding to the insect cuticle drive the systematic integrated disease development events in target host to impart pathogenesis. However, there is growing evidence that virulence of the pathogen is directly related with proteolytic enzymes including metalloproteinases, chymotrypsin-like proteinases and subtilisin-like proteinases. Successful host pathogenesis is the selection of right set of virulence-related proteinases, which evolved as a result of host-pathogen coevolution.

Laboratory Tests for Legionnaire's Disease.

PubMed

Dunne, W Michael; Picot, Nathalie; van Belkum, Alex

2017-03-01

Legionella pneumophila is one of the more recently discovered bacterial pathogens of humans. The last 2 decades have seen tremendous progress in the evolution of diagnostic tests, for detection and characterization of this pathogen and for defining the host response to infection. This has generated several diagnostic tools that span the range from simple immunologic assays to modern genome sequencing. This review describes the state of affairs of this continuously evolving field regarding the diagnosis of Legionnaire's disease and covers detection, assessment of antibiotic susceptibility, and epidemiologic characterization of isolates of L pneumophila and other pathogenic species within the genus. Copyright © 2016 Elsevier Inc. All rights reserved.

Viral receptor-binding site antibodies with diverse germline origins.

PubMed

Schmidt, Aaron G; Therkelsen, Matthew D; Stewart, Shaun; Kepler, Thomas B; Liao, Hua-Xin; Moody, M Anthony; Haynes, Barton F; Harrison, Stephen C

2015-05-21

Vaccines for rapidly evolving pathogens will confer lasting immunity if they elicit antibodies recognizing conserved epitopes, such as a receptor-binding site (RBS). From characteristics of an influenza-virus RBS-directed antibody, we devised a signature motif to search for similar antibodies. We identified, from three vaccinees, over 100 candidates encoded by 11 different VH genes. Crystal structures show that antibodies in this class engage the hemagglutinin RBS and mimic binding of the receptor, sialic acid, by supplying a critical dipeptide on their projecting, heavy-chain third complementarity determining region. They share contacts with conserved, receptor-binding residues but contact different residues on the RBS periphery, limiting the likelihood of viral escape when several such antibodies are present. These data show that related modes of RBS recognition can arise from different germline origins and mature through diverse affinity maturation pathways. Immunogens focused on an RBS-directed response will thus have a broad range of B cell targets. Copyright © 2015 Elsevier Inc. All rights reserved.

Biosensor for the detection of Listeria monocytogenes: emerging trends.

PubMed

Soni, Dharmendra Kumar; Ahmad, Rafiq; Dubey, Suresh Kumar

2018-05-23

The early detection of Listeria monocytogenes (L. monocytogenes) and understanding the disease burden is of paramount interest. The failure to detect pathogenic bacteria in the food industry may have terrible consequences, and poses deleterious effects on human health. Therefore, integration of methods to detect and trace the route of pathogens along the entire food supply network might facilitate elucidation of the main contamination sources. Recent research interest has been oriented towards the development of rapid and affordable pathogen detection tools/techniques. An innovative and new approach like biosensors has been quite promising in revealing the foodborne pathogens. In spite of the existing knowledge, advanced research is still needed to substantiate the expeditious nature and sensitivity of biosensors for rapid and in situ analysis of foodborne pathogens. This review summarizes recent developments in optical, piezoelectric, cell-based, and electrochemical biosensors for Listeria sp. detection in clinical diagnostics, food analysis, and environmental monitoring, and also lists their drawbacks and advantages.

Post-translational modification of host proteins in pathogen-triggered defence signalling in plants.

PubMed

Stulemeijer, Iris J E; Joosten, Matthieu H A J

2008-07-01

Microbial plant pathogens impose a continuous threat to global food production. Similar to animals, an innate immune system allows plants to recognize pathogens and swiftly activate defence. To activate a rapid response, receptor-mediated pathogen perception and subsequent downstream signalling depends on post-translational modification (PTM) of components essential for defence signalling. We discuss different types of PTMs that play a role in mounting plant immunity, which include phosphorylation, glycosylation, ubiquitination, sumoylation, nitrosylation, myristoylation, palmitoylation and glycosylphosphatidylinositol (GPI)-anchoring. PTMs are rapid, reversible, controlled and highly specific, and provide a tool to regulate protein stability, activity and localization. Here, we give an overview of PTMs that modify components essential for defence signalling at the site of signal perception, during secondary messenger production and during signalling in the cytoplasm. In addition, we discuss effectors from pathogens that suppress plant defence responses by interfering with host PTMs.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

PubMed Central

Johnson, Timothy J.; Ricke, Steven C.; Nayak, Rajesh; Danzeisen, Jessica

2013-01-01

SUMMARY Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's immune system and commensal organisms that are present. Thus, the factors that impact the ability of Salmonella to colonize a particular host species, such as chickens, are complex and multifactorial, involving the host, the pathogen, and extrinsic pressures. It is the interplay of these factors which leads to the differences in host ranges that we observe today. PMID:24296573

Genetic and Genomic Architecture of the Evolution of Resistance to Antifungal Drug Combinations

PubMed Central

Hill, Jessica A.; Ammar, Ron; Torti, Dax; Nislow, Corey; Cowen, Leah E.

2013-01-01

The evolution of drug resistance in fungal pathogens compromises the efficacy of the limited number of antifungal drugs. Drug combinations have emerged as a powerful strategy to enhance antifungal efficacy and abrogate drug resistance, but the impact on the evolution of drug resistance remains largely unexplored. Targeting the molecular chaperone Hsp90 or its downstream effector, the protein phosphatase calcineurin, abrogates resistance to the most widely deployed antifungals, the azoles, which inhibit ergosterol biosynthesis. Here, we evolved experimental populations of the model yeast Saccharomyces cerevisiae and the leading human fungal pathogen Candida albicans with azole and an inhibitor of Hsp90, geldanamycin, or calcineurin, FK506. To recapitulate a clinical context where Hsp90 or calcineurin inhibitors could be utilized in combination with azoles to render resistant pathogens responsive to treatment, the evolution experiment was initiated with strains that are resistant to azoles in a manner that depends on Hsp90 and calcineurin. Of the 290 lineages initiated, most went extinct, yet 14 evolved resistance to the drug combination. Drug target mutations that conferred resistance to geldanamycin or FK506 were identified and validated in five evolved lineages. Whole-genome sequencing identified mutations in a gene encoding a transcriptional activator of drug efflux pumps, PDR1, and a gene encoding a transcriptional repressor of ergosterol biosynthesis genes, MOT3, that transformed azole resistance of two lineages from dependent on calcineurin to independent of this regulator. Resistance also arose by mutation that truncated the catalytic subunit of calcineurin, and by mutation in LCB1, encoding a sphingolipid biosynthetic enzyme. Genome analysis revealed extensive aneuploidy in four of the C. albicans lineages. Thus, we identify molecular determinants of the transition of azole resistance from calcineurin dependence to independence and establish multiple mechanisms by which resistance to drug combinations evolves, providing a foundation for predicting and preventing the evolution of drug resistance. PMID:23593013

Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood.

PubMed

Nölling, Jörk; Rapireddy, Srinivas; Amburg, Joel I; Crawford, Elizabeth M; Prakash, Ranjit A; Rabson, Arthur R; Tang, Yi-Wei; Singer, Alon

2016-04-19

Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention. Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need. Copyright © 2016 Nölling et al.

Differing House Finch Cytokine Expression Responses to Original and Evolved Isolates of Mycoplasma gallisepticum.

PubMed

Vinkler, Michal; Leon, Ariel E; Kirkpatrick, Laila; Dalloul, Rami A; Hawley, Dana M

2018-01-01

The recent emergence of the poultry bacterial pathogen Mycoplasma gallisepticum (MG) in free-living house finches ( Haemorhous mexicanus ), which causes mycoplasmal conjunctivitis in this passerine bird species, resulted in a rapid coevolutionary arms-race between MG and its novel avian host. Despite extensive research on the ecological and evolutionary dynamics of this host-pathogen system over the past two decades, the immunological responses of house finches to MG infection remain poorly understood. We developed seven new probe-based one-step quantitative reverse transcription polymerase chain reaction assays to investigate mRNA expression of house finch cytokine genes ( IL1B, IL6, IL10, IL18, TGFB2, TNFSF15 , and CXCLi2 , syn. IL8L ). These assays were then used to describe cytokine transcription profiles in a panel of 15 house finch tissues collected at three distinct time points during MG infection. Based on initial screening that indicated strong pro-inflammatory cytokine expression during MG infection at the periorbital sites in particular, we selected two key house finch tissues for further characterization: the nictitating membrane, i.e., the internal eyelid in direct contact with MG, and the Harderian gland, the secondary lymphoid tissue responsible for regulation of periorbital immunity. We characterized cytokine responses in these two tissues for 60 house finches experimentally inoculated either with media alone (sham) or one of two MG isolates: the earliest known pathogen isolate from house finches (VA1994) or an evolutionarily more derived isolate collected in 2006 (NC2006), which is known to be more virulent. We show that the more derived and virulent isolate NC2006, relative to VA1994, triggers stronger local inflammatory cytokine signaling, with peak cytokine expression generally occurring 3-6 days following MG inoculation. We also found that the extent of pro-inflammatory interleukin 1 beta signaling was correlated with conjunctival MG loads and the extent of clinical signs of conjunctivitis, the main pathological effect of MG in house finches. These results suggest that the pathogenicity caused by MG infection in house finches is largely mediated by host pro-inflammatory immune responses, with important implications for the dynamics of host-pathogen coevolution.

Bacillus cereus cell response upon exposure to acid environment: toward the identification of potential biomarkers

PubMed Central

Desriac, Noémie; Broussolle, Véronique; Postollec, Florence; Mathot, Anne-Gabrielle; Sohier, Danièle; Coroller, Louis; Leguerinel, Ivan

2013-01-01

Microorganisms are able to adapt to different environments and evolve rapidly, allowing them to cope with their new environments. Such adaptive response and associated protections toward other lethal stresses, is a crucial survival strategy for a wide spectrum of microorganisms, including food spoilage bacteria, pathogens, and organisms used in functional food applications. The growing demand for minimal processed food yields to an increasing use of combination of hurdles or mild preservation factors in the food industry. A commonly used hurdle is low pH which allows the decrease in bacterial growth rate but also the inactivation of pathogens or spoilage microorganisms. Bacillus cereus is a well-known food-borne pathogen leading to economical and safety issues in food industry. Because survival mechanisms implemented will allow bacteria to cope with environmental changes, it is important to provide understanding of B. cereus stress response. Thus this review deals with the adaptive traits of B. cereus cells facing to acid stress conditions. The acid stress response of B. cereus could be divided into four groups (i) general stress response (ii) pH homeostasis, (iii) metabolic modifications and alkali production and (iv) secondary oxidative stress response. This current knowledge may be useful to understand how B. cereus cells may cope to acid environment such as encountered in food products and thus to find some molecular biomarkers of the bacterial behavior. These biomarkers could be furthermore used to develop new microbial behavior prediction tools which can provide insights into underlying molecular physiological states which govern the behavior of microorganisms and thus opening the avenue toward the detection of stress adaptive behavior at an early stage and the control of stress-induced resistance throughout the food chain. PMID:24106490

Rapidly Evolving Toll-3/4 Genes Encode Male-Specific Toll-Like Receptors in Drosophila.

PubMed

Levin, Tera C; Malik, Harmit S

2017-09-01

Animal Toll-like receptors (TLRs) have evolved through a pattern of duplication and divergence. Whereas mammalian TLRs directly recognize microbial ligands, Drosophila Tolls bind endogenous ligands downstream of both developmental and immune signaling cascades. Here, we find that most Toll genes in Drosophila evolve slowly with little gene turnover (gains/losses), consistent with their important roles in development and indirect roles in microbial recognition. In contrast, we find that the Toll-3/4 genes have experienced an unusually rapid rate of gene gains and losses, resulting in lineage-specific Toll-3/4s and vastly different gene repertoires among Drosophila species, from zero copies (e.g., D. mojavensis) to nineteen copies (e.g., D. willistoni). In D. willistoni, we find strong evidence for positive selection in Toll-3/4 genes, localized specifically to an extracellular region predicted to overlap with the binding site of Spätzle, the only known ligand of insect Tolls. However, because Spätzle genes are not experiencing similar selective pressures, we hypothesize that Toll-3/4s may be rapidly evolving because they bind to a different ligand, akin to TLRs outside of insects. We further find that most Drosophila Toll-3/4 genes are either weakly expressed or expressed exclusively in males, specifically in the germline. Unlike other Toll genes in D. melanogaster, Toll-3, and Toll-4 have apparently escaped from essential developmental roles, as knockdowns have no substantial effects on viability or male fertility. Based on these findings, we propose that the Toll-3/4 genes represent an exceptionally rapidly evolving lineage of Drosophila Toll genes, which play an unusual, as-yet-undiscovered role in the male germline. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Rapidly Evolving Toll-3/4 Genes Encode Male-Specific Toll-Like Receptors in Drosophila

PubMed Central

Levin, Tera C.; Malik, Harmit S.

2017-01-01

Abstract Animal Toll-like receptors (TLRs) have evolved through a pattern of duplication and divergence. Whereas mammalian TLRs directly recognize microbial ligands, Drosophila Tolls bind endogenous ligands downstream of both developmental and immune signaling cascades. Here, we find that most Toll genes in Drosophila evolve slowly with little gene turnover (gains/losses), consistent with their important roles in development and indirect roles in microbial recognition. In contrast, we find that the Toll-3/4 genes have experienced an unusually rapid rate of gene gains and losses, resulting in lineage-specific Toll-3/4s and vastly different gene repertoires among Drosophila species, from zero copies (e.g., D. mojavensis) to nineteen copies (e.g., D. willistoni). In D. willistoni, we find strong evidence for positive selection in Toll-3/4 genes, localized specifically to an extracellular region predicted to overlap with the binding site of Spätzle, the only known ligand of insect Tolls. However, because Spätzle genes are not experiencing similar selective pressures, we hypothesize that Toll-3/4s may be rapidly evolving because they bind to a different ligand, akin to TLRs outside of insects. We further find that most Drosophila Toll-3/4 genes are either weakly expressed or expressed exclusively in males, specifically in the germline. Unlike other Toll genes in D. melanogaster, Toll-3, and Toll-4 have apparently escaped from essential developmental roles, as knockdowns have no substantial effects on viability or male fertility. Based on these findings, we propose that the Toll-3/4 genes represent an exceptionally rapidly evolving lineage of Drosophila Toll genes, which play an unusual, as-yet-undiscovered role in the male germline. PMID:28541576

A fibre based triature interferometer for measuring rapidly evolving, ablatively driven plasma densities

NASA Astrophysics Data System (ADS)

Macdonald, J.; Bland, S. N.; Threadgold, J.

2015-08-01

We report on the first use of a fibre interferometer incorporating triature analysis for measuring rapidly evolving plasma densities of ne ˜ 1013/cm3 and above, such as those produced by simple coaxial plasma guns. The resultant system is extremely portable, easy to field in experiments, relatively cheap to produce, and—with the exception of a small open area in which the plasma is sampled—safe in operation as all laser light is enclosed.

Roles of small RNAs in plant disease resistance.

PubMed

Yang, Li; Huang, Hai

2014-10-01

The interaction between plants and pathogens represents a dynamic competition between a robust immune system and efficient infectious strategies. Plant innate immunity is composed of complex and highly regulated molecular networks, which can be triggered by the perception of either conserved or race-specific pathogenic molecular signatures. Small RNAs are emerging as versatile regulators of plant development, growth and response to biotic and abiotic stresses. They act in different tiers of plant immunity, including the pathogen-associated molecular pattern-triggered and the effector-triggered immunity. On the other hand, pathogens have evolved effector molecules to suppress or hijack the host small RNA pathways. This leads to an arms race between plants and pathogens at the level of small RNA-mediated defense. Here, we review recent advances in small RNA-mediated defense responses and discuss the challenging questions in this area. © 2014 Institute of Botany, Chinese Academy of Sciences.

Subverting Toll-Like Receptor Signaling by Bacterial Pathogens

PubMed Central

McGuire, Victoria A.; Arthur, J. Simon C.

2015-01-01

Pathogenic bacteria are detected by pattern-recognition receptors (PRRs) expressed on innate immune cells, which activate intracellular signal transduction pathways to elicit an immune response. Toll-like receptors are, perhaps, the most studied of the PRRs and can activate the mitogen-activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB) pathways. These pathways are critical for mounting an effective immune response. In order to evade detection and promote virulence, many pathogens subvert the host immune response by targeting components of these signal transduction pathways. This mini-review highlights the diverse mechanisms that bacterial pathogens have evolved to manipulate the innate immune response, with a particular focus on those that target MAPK and NF-κB signaling pathways. Understanding the elaborate strategies that pathogens employ to subvert the immune response not only highlights the importance of these proteins in mounting effective immune responses, but may also identify novel approaches for treatment or prevention of infection. PMID:26648936

Regulating the Intersection of Metabolism and Pathogenesis in Gram-positive Bacteria

PubMed Central

RICHARDSON, ANTHONY R.; SOMERVILLE, GREG A.; SONENSHEIN, ABRAHAM L.

2015-01-01

Pathogenic bacteria must contend with immune systems that actively restrict the availability of nutrients and cofactors, and create a hostile growth environment. To deal with these hostile environments, pathogenic bacteria have evolved or acquired virulence determinants that aid in the acquisition of nutrients. This connection between pathogenesis and nutrition may explain why regulators of metabolism in nonpathogenic bacteria are used by pathogenic bacteria to regulate both metabolism and virulence. Such coordinated regulation is presumably advantageous because it conserves carbon and energy by aligning synthesis of virulence determinants with the nutritional environment. In Gram-positive bacterial pathogens, at least three metabolite-responsive global regulators, CcpA, CodY, and Rex, have been shown to coordinate the expression of metabolism and virulence genes. In this chapter, we discuss how environmental challenges alter metabolism, the regulators that respond to this altered metabolism, and how these regulators influence the host-pathogen interaction. PMID:26185086

Development of Untargeted Metabolomics Methods for the Rapid Detection of Pathogenic Naegleria fowleri.

PubMed

Yu, Zhihao; Miller, Haylea C; Puzon, Geoffrey J; Clowers, Brian H

2017-04-18

Despite comparatively low levels of infection, primary amoebic meningoencephalitis (PAM) induced by Naegleria fowleri is extremely lethal, with mortality rates above 95%. As a thermophile, this organism is often found in moderate-to-warm climates and has the potential to colonize drinking water distribution systems (DWDSs). Current detection approaches require days to obtain results, whereas swift corrective action can maximize the benefit of public health. Presently, there is little information regarding the underlying in situ metabolism for this amoeba but the potential exists to exploit differentially expressed metabolic signatures as a rapid detection technique. This research outlines the biochemical profiles of selected pathogenic and nonpathogenic Naegleria in vitro using an untargeted metabolomics approach to identify a panel of diagnostically meaningful compounds that may enable rapid detection of viable pathogenic N. fowleri and augment results from traditional monitoring approaches.

Emerging horizons for tick-borne pathogens: from the ‘one pathogen–one disease’ vision to the pathobiome paradigm

PubMed Central

Vayssier-Taussat, Muriel; Kazimirova, Maria; Hubalek, Zdenek; Hornok, Sándor; Farkas, Robert; Cosson, Jean-François; Bonnet, Sarah; Vourch, Gwenaël; Gasqui, Patrick; Mihalca, Andrei Daniel; Plantard, Olivier; Silaghi, Cornelia; Cutler, Sally; Rizzoli, Annapaola

2015-01-01

Ticks, as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human and animal health in Europe. Recent applications of new technology revealed the complexity of the tick microbiome, which may affect its vectorial capacity. Appreciation of these complex systems is expanding our understanding of tick-borne pathogens, leading us to evolve a more integrated view that embraces the ‘pathobiome’; the pathogenic agent integrated within its abiotic and biotic environments. In this review, we will explore how this new vision will revolutionize our understanding of tick-borne diseases. We will discuss the implications in terms of future research approaches that will enable us to efficiently prevent and control the threat posed by ticks. PMID:26610021

Long-Term Evolution of Burkholderia multivorans during a Chronic Cystic Fibrosis Infection Reveals Shifting Forces of Selection

PubMed Central

Silva, Inês N.; Santos, Mário R.; Zlosnik, James E. A.; Speert, David P.; Buskirk, Sean W.; Bruger, Eric L.; Waters, Christopher M.

2016-01-01

ABSTRACT Burkholderia multivorans is an opportunistic pathogen capable of causing severe disease in patients with cystic fibrosis (CF). Patients may be chronically infected for years, during which the bacterial population evolves in response to unknown forces. Here we analyze the genomic and functional evolution of a B. multivorans infection that was sequentially sampled from a CF patient over 20 years. The population diversified into at least four primary, coexisting clades with distinct evolutionary dynamics. The average substitution rate was only 2.4 mutations/year, but notably, some lineages evolved more slowly, whereas one diversified more rapidly by mostly nonsynonymous mutations. Ten loci, mostly involved in gene expression regulation and lipid metabolism, acquired three or more independent mutations and define likely targets of selection. Further, a broad range of phenotypes changed in association with the evolved mutations; they included antimicrobial resistance, biofilm regulation, and the presentation of lipopolysaccharide O-antigen repeats, which was directly caused by evolved mutations. Additionally, early isolates acquired mutations in genes involved in cyclic di-GMP (c-di-GMP) metabolism that associated with increased c-di-GMP intracellular levels. Accordingly, these isolates showed lower motility and increased biofilm formation and adhesion to CFBE41o− epithelial cells than the initial isolate, and each of these phenotypes is an important trait for bacterial persistence. The timing of the emergence of this clade of more adherent genotypes correlated with the period of greatest decline in the patient’s lung function. All together, our observations suggest that selection on B. multivorans populations during long-term colonization of CF patient lungs either directly or indirectly targets adherence, metabolism, and changes in the cell envelope related to adaptation to the biofilm lifestyle. IMPORTANCE Bacteria may become genetically and phenotypically diverse during long-term colonization of cystic fibrosis (CF) patient lungs, yet our understanding of within-host evolutionary processes during these infections is lacking. Here we combined current genome sequencing technologies and detailed phenotypic profiling of the opportunistic pathogen Burkholderia multivorans using sequential isolates sampled from a CF patient over 20 years. The evolutionary history of these isolates highlighted bacterial genes and pathways that were likely subject to strong selection within the host and were associated with altered phenotypes, such as biofilm production, motility, and antimicrobial resistance. Importantly, multiple lineages coexisted for years or even decades within the infection, and the period of diversification within the dominant lineage was associated with deterioration of the patient’s lung function. Identifying traits under strong selection during chronic infection not only sheds new light onto Burkholderia evolution but also sets the stage for tailored therapeutics targeting the prevailing lineages associated with disease progression. PMID:27822534

Multiplex and label-free screening of foodborne pathogens using surface plasmon resonance imaging

USDA-ARS?s Scientific Manuscript database

In order to protect outbreaks caused by foodborne pathogens, more rapid and efficient methods are needed for pathogen screening from food samples. Surface plasmon resonance imaging (SPRi) is an emerging optical technique, which allows for label-free screening of multiple targets simultaneously with ...

A Spectral Mapping Signature for the Rapid Ohia Death (ROD) Pathogen in Hawaiian Forests

USDA-ARS?s Scientific Manuscript database

Pathogenic invasions are a major disruptive source of change in both agricultural and natural ecosystems. In forests, fungal pathogens can kill habitat-generating plant species such as canopy trees, but methods for remote detection, mapping and monitoring of such outbreaks are poorly developed. Cera...

Real time detection of ESKAPE pathogens by a nitroreductase-triggered fluorescence turn-on probe.

PubMed

Xu, Shengnan; Wang, Qinghua; Zhang, Qingyang; Zhang, Leilei; Zuo, Limin; Jiang, Jian-Dong; Hu, Hai-Yu

2017-10-18

The identification of bacterial pathogens is the critical first step in conquering infection diseases. A novel turn-on fluorescent probe for the selective sensing of nitroreductase (NTR) activity and its initial applications in rapid, real-time detection and identification of ESKAPE pathogens have been reported.

OPPORTUNISTIC ASPERGILLUS PATHOGENS MEASURED IN HOME AND HOSPITAL TAP WATER BY MOLD SPECIFIC QUANTITATIVE PCR (MSQPCR)

EPA Science Inventory

Opportunistic fungal pathogens are a concern because of the increasing number of immunocompromised patients. The goal of this research was to test a simple extraction method and rapid quantitative PCR (QPCR) measurement of the occurrence of potential pathogens, Aspergillus fumiga...

Virulence factors and resistance mechanisms of Serratia marcescens. A short review.

PubMed

Rodrigues, Ana P; Holanda, A R M; Lustosa, G P; Nóbrega, S M B; Santana, Willma J; Souza, Luciana B S; Coutinho, H D M

2006-03-01

Serratia marcescens, a Gram-negative bacillus that belongs to the family Enterobacteriaceae, is a human opportunistic pathogen bacterium that causes many diseases, such as urinary tract infections, respiratory tract infections, bacteremia, conjunctivitis, endocarditis, meningitis and wound infections. Many plasmides that confers multi-drug resistance were discovered, such as virulence factors, like cytotoxins that damage epithelial cells. The main topic of this paper presents a review about the molecular traits evolved in the pathogenic processes mediated by Serratia and its mechanism of resistance to drugs.

Pathogen trafficking pathways and host phosphoinositide metabolism.

PubMed

Weber, Stefan S; Ragaz, Curdin; Hilbi, Hubert

2009-03-01

Phosphoinositide (PI) glycerolipids are key regulators of eukaryotic signal transduction, cytoskeleton architecture and membrane dynamics. The host cell PI metabolism is targeted by intracellular bacterial pathogens, which evolved intricate strategies to modulate uptake processes and vesicle trafficking pathways. Upon entering eukaryotic host cells, pathogenic bacteria replicate in distinct vacuoles or in the host cytoplasm. Vacuolar pathogens manipulate PI levels to mimic or modify membranes of subcellular compartments and thereby establish their replicative niche. Legionella pneumophila, Brucella abortus, Mycobacterium tuberculosis and Salmonella enterica translocate effector proteins into the host cell, some of which anchor to the vacuolar membrane via PIs or enzymatically turnover PIs. Cytoplasmic pathogens target PI metabolism at the plasma membrane, thus modulating their uptake and antiapoptotic signalling pathways. Employing this strategy, Shigella flexneri directly injects a PI-modifying effector protein, while Listeria monocytogenes exploits PI metabolism indirectly by binding to transmembrane receptors. Thus, regardless of the intracellular lifestyle of the pathogen, PI metabolism is critically involved in the interactions with host cells.

Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection

PubMed Central

Sistrunk, Jeticia R.; Nickerson, Kourtney P.; Chanin, Rachael B.; Rasko, David A.

2016-01-01

SUMMARY Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens. PMID:27464994

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

PubMed Central

de la Fuente, José; Antunes, Sandra; Bonnet, Sarah; Cabezas-Cruz, Alejandro; Domingos, Ana G.; Estrada-Peña, Agustín; Johnson, Nicholas; Kocan, Katherine M.; Mansfield, Karen L.; Nijhof, Ard M.; Papa, Anna; Rudenko, Nataliia; Villar, Margarita; Alberdi, Pilar; Torina, Alessandra; Ayllón, Nieves; Vancova, Marie; Golovchenko, Maryna; Grubhoffer, Libor; Caracappa, Santo; Fooks, Anthony R.; Gortazar, Christian; Rego, Ryan O. M.

2017-01-01

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases. PMID:28439499

Enzyme-driven metabolomic screening: a proof-of-principle method for discovery of plant defence compounds targeted by pathogens.

PubMed

Carere, Jason; Colgrave, Michelle L; Stiller, Jiri; Liu, Chunji; Manners, John M; Kazan, Kemal; Gardiner, Donald M

2016-11-01

Plants produce a variety of secondary metabolites to defend themselves from pathogen attack, while pathogens have evolved to overcome plant defences by producing enzymes that degrade or modify these defence compounds. However, many compounds targeted by pathogen enzymes currently remain enigmatic. Identifying host compounds targeted by pathogen enzymes would enable us to understand the potential importance of such compounds in plant defence and modify them to make them insensitive to pathogen enzymes. Here, a proof of concept metabolomics-based method was developed to discover plant defence compounds modified by pathogens using two pathogen enzymes with known targets in wheat and tomato. Plant extracts treated with purified pathogen enzymes were subjected to LC-MS, and the relative abundance of metabolites before and after treatment were comparatively analysed. Using two enzymes from different pathogens the in planta targets could be found by combining relatively simple enzymology with the power of untargeted metabolomics. Key to the method is dataset simplification based on natural isotope occurrence and statistical filtering, which can be scripted. The method presented here will aid in our understanding of plant-pathogen interactions and may lead to the development of new plant protection strategies. © 2016 CSIRO. New Phytologist © 2016 New Phytologist Trust.

Pathogen profiling for disease management and surveillance.

PubMed

Sintchenko, Vitali; Iredell, Jonathan R; Gilbert, Gwendolyn L

2007-06-01

The usefulness of rapid pathogen genotyping is widely recognized, but its effective interpretation and application requires integration into clinical and public health decision-making. How can pathogen genotyping data best be translated to inform disease management and surveillance? Pathogen profiling integrates microbial genomics data into communicable disease control by consolidating phenotypic identity-based methods with DNA microarrays, proteomics, metabolomics and sequence-based typing. Sharing data on pathogen profiles should facilitate our understanding of transmission patterns and the dynamics of epidemics.

Rapid analysis of foodborne pathogens by surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Sengupta, Atanu; Shende, Chetan; Huang, Hermes; Farquharson, Stuart; Inscore, Frank

2012-05-01

Foodborne diseases resulting from Campylobacter, Escherichia, Listeria, Salmonella, Shigella and Vibrio species affect as many as 76 million persons in the United States each year, resulting in 325,000 hospitalizations and 5,000 deaths. The challenge to preventing distribution and consumption of contaminated foods lies in the fact that just a few bacterial cells can rapidly multiply to millions, reaching infectious doses within a few days. Unfortunately, current methods used to detect these few cells rely on lengthy growth enrichment steps that take a similar amount of time (1 to 4 days). Consequently, there is a critical need for an analyzer that can rapidly extract and detect foodborne pathogens in 1-2 hours (not days), at 100 colony forming units per gram of food, and with a specificity that differentiates from indigenous microflora, so that false alarms are eliminated. In an effort to meet this need, we have been developing a sample system that extracts such pathogens from food, selectively binds these pathogens, and produces surface-enhanced Raman spectra (SERS). Here we present preliminary SERS measurements of Listeria and Salmonella.

Advances in molecular-based diagnostics in meeting crop biosecurity and phytosanitary issues.

PubMed

Schaad, Norman W; Frederick, Reid D; Shaw, Joe; Schneider, William L; Hickson, Robert; Petrillo, Michael D; Luster, Douglas G

2003-01-01

Awareness of crop biosecurity and phytosanitation has been heightened since 9/11 and the unresolved anthrax releases in October 2001. Crops are highly vulnerable to accidental or deliberate introductions of crop pathogens from outside U.S. borders. Strategic thinking about protection against deliberate or accidental release of a plant pathogen is an urgent priority. Rapid detection will be the key to success. This review summarizes recent progress in the development of rapid real-time PCR protocols and evaluates their effectiveness in a proposed nationwide network of diagnostic laboratories that will facilitate rapid diagnostics and improved communication.

Evaluation of High-Resolution Melting Curve Analysis of Ligation-Mediated Real-Time PCR, a Rapid Method for Epidemiological Typing of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter Species) Pathogens

PubMed Central

Ryberg, Anna; Billström, Hanna; Hällgren, Anita; Nilsson, Lennart E.; Marklund, Britt-Inger; Olsson-Liljequist, Barbro; Schön, Thomas

2014-01-01

A single-tube method, ligation-mediated real-time PCR high-resolution melt analysis (LMqPCR HRMA), was modified for the rapid typing of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens. A 97% agreement (60/62 isolates) was achieved in comparison to pulsed-field gel electrophoresis (PFGE) results, which indicates that LMqPCR HRMA is a rapid and accurate screening tool for monitoring nosocomial outbreaks. PMID:25232168

RAPIDLY EVOLVING AND LUMINOUS TRANSIENTS DRIVEN BY NEWLY BORN NEUTRON STARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yun-Wei; Li, Shao-Ze; Dai, Zi-Gao, E-mail: yuyw@mail.ccnu.edu.cn

2015-06-10

We provide a general analysis on the properties of the emitting material of some rapidly evolving and luminous transients discovered recently with the Pan-STARRS1 Medium Deep Survey. It was found that these transients are probably produced by a low-mass non-relativistic outflow that is continuously powered by a newly born, rapidly spinning, and highly magnetized neutron star (NS). Such a system could originate from an accretion-induced collapse of a white dwarf or a merger of an NS–NS binary. Therefore, observations of these transients would be helpful for constraining white dwarf and NS physics and/or for searching and identifying gravitational wave signals frommore » the mergers.« less

Apoplastic effectors secreted by two unrelated eukaryotic plant pathogens target the tomato defense protease Rcr3.

PubMed

Song, Jing; Win, Joe; Tian, Miaoying; Schornack, Sebastian; Kaschani, Farnusch; Ilyas, Muhammad; van der Hoorn, Renier A L; Kamoun, Sophien

2009-02-03

Current models of plant-pathogen interactions stipulate that pathogens secrete effector proteins that disable plant defense components known as virulence targets. Occasionally, the perturbations caused by these effectors trigger innate immunity via plant disease resistance proteins as described by the "guard hypothesis." This model is nicely illustrated by the interaction between the fungal plant pathogen Cladosporium fulvum and tomato. C. fulvum secretes a protease inhibitor Avr2 that targets the tomato cysteine protease Rcr3(pim). In plants that carry the resistance protein Cf2, Rcr3(pim) is required for resistance to C. fulvum strains expressing Avr2, thus fulfilling one of the predictions of the guard hypothesis. Another prediction of the guard hypothesis has not yet been tested. Considering that virulence targets are important components of defense, different effectors from unrelated pathogens are expected to evolve to disable the same host target. In this study we confirm this prediction using a different pathogen of tomato, the oomycete Phytophthora infestans that is distantly related to fungi such as C. fulvum. This pathogen secretes an array of protease inhibitors including EPIC1 and EPIC2B that inhibit tomato cysteine proteases. Here we show that, similar to Avr2, EPIC1 and EPIC2B bind and inhibit Rcr3(pim). However, unlike Avr2, EPIC1 and EPIC2B do not trigger hypersensitive cell death or defenses on Cf-2/Rcr3(pim) tomato. We also found that the rcr3-3 mutant of tomato that carries a premature stop codon in the Rcr3 gene exhibits enhanced susceptibility to P. infestans, suggesting a role for Rcr3(pim) in defense. In conclusion, our findings fulfill a key prediction of the guard hypothesis and suggest that the effectors Avr2, EPIC1, and EPIC2B secreted by two unrelated pathogens of tomato target the same defense protease Rcr3(pim). In contrast to C. fulvum, P. infestans appears to have evolved stealthy effectors that carry inhibitory activity without triggering plant innate immunity.

A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts

PubMed Central

Gerwien, Franziska; Safyan, Abu; Wisgott, Stephanie; Hille, Fabrice; Kaemmer, Philipp; Linde, Jörg; Brunke, Sascha; Kasper, Lydia

2016-01-01

ABSTRACT Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker’s yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. PMID:27795405

Evaluation of rapid SYS system as screen for Yersinia enterocolitica in the United States.

PubMed Central

Mele, L; Nadler, H; Gomez, S

1987-01-01

Clinical isolates (n = 150) from stool specimens were selected for evaluation of the Rapid SYS system (Analytab Products, Plainview, N.Y.) as a screening test for Shigella spp., Yersinia enterocolitica, and Salmonella spp. The Gram-Negative Identification Card (Vitek Systems, Inc., Hazelwood, Mo.) was used for identification. Although acceptable performance of the Rapid SYS system was described, the interpretative criteria provided by the vendor for previous studies led to inappropriate screening for Y. enterocolitica, particularly biotype 1. When corrected screening criteria were used for the present study, the sensitivity for the detection of 76 enteric pathogens was 98.7%. Of the 76 pathogens, 1 of 21 Shigella spp. was not detected. However, specificity was only 16.6% when 72 selected nonpathogens frequently encountered in stools were eliminated. Although the Rapid SYS system can identify Shigella spp., Y. enterocolitica, and Salmonella spp., only phenylalanine deaminase-producing and cytochrome oxidase-producing organisms can be eliminated from additional testing. Therefore, the Rapid SYS system cannot be used as a three-pathogen screen in the United States or in other geographic locales where Y. enterocolitica biotype 1 may be encountered. PMID:3323232

BIOTIC FACTORS IN AMPHIBIAN POPULATION DECLINES

EPA Science Inventory

Amphibians evolved in, and continue to exist in, habitats that are replete with many other organisms. Some of these organisms serve as prey for amphibians and others interact with amphibians as predators, competitors, pathogens, or symbionts. Still other organisms in their enviro...

Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents

DTIC Science & Technology

1997-11-01

status can sometimes be reflected in the infectious potential or drug resistance of those pathogens. For example, in Mycobacterium tuberculosis ... Mycobacterium tuberculosis , its antibiotic resistance and prediction of pathogenicity amongst Mycobacterium spp. based on signature lipid biomarkers ...TITLE AND SUBTITLE Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents 5a. CONTRACT NUMBER 5b

A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection.

PubMed

Zuo, Peng; Li, XiuJun; Dominguez, Delfina C; Ye, Bang-Ce

2013-10-07

Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL(-1). We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step 'turn on' pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens.

A PDMS/paper/glass hybrid microfluidic biochip integrated with aptamer-functionalized graphene oxide nano-biosensors for one-step multiplexed pathogen detection

PubMed Central

Zuo, Peng; Dominguez, Delfina C.; Ye, Bang-Ce

2014-01-01

Infectious pathogens often cause serious public health concerns throughout the world. There is an increasing demand for simple, rapid and sensitive approaches for multiplexed pathogen detection. In this paper we have developed a polydimethylsiloxane (PDMS)/paper/glass hybrid microfluidic system integrated with aptamer-functionalized graphene oxide (GO) nano-biosensors for simple, one-step, multiplexed pathogen detection. The paper substrate used in this hybrid microfluidic system facilitated the integration of aptamer biosensors on the microfluidic biochip, and avoided complicated surface treatment and aptamer probe immobilization in a PDMS or glass-only microfluidic system. Lactobacillus acidophilus was used as a bacterium model to develop the microfluidic platform with a detection limit of 11.0 cfu mL−1. We have also successfully extended this method to the simultaneous detection of two infectious pathogens - Staphylococcus aureus and Salmonella enterica. This method is simple and fast. The one-step ‘turn on’ pathogen assay in a ready-to-use microfluidic device only takes ~10 min to complete on the biochip. Furthermore, this microfluidic device has great potential in rapid detection of a wide variety of different other bacterial and viral pathogens. PMID:23929394

Buried treasure: evolutionary perspectives on microbial iron piracy

PubMed Central

Barber, Matthew F.; Elde, Nels C.

2015-01-01

Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease. PMID:26431675

Mycoplasmas and their host: emerging and re-emerging minimal pathogens.

PubMed

Citti, Christine; Blanchard, Alain

2013-04-01

Commonly known as mycoplasmas, bacteria of the class Mollicutes include the smallest and simplest life forms capable of self replication outside of a host. Yet, this minimalism hides major human and animal pathogens whose prevalence and occurrence have long been underestimated. Owing to advances in sequencing methods, large data sets have become available for a number of mycoplasma species and strains, providing new diagnostic approaches, typing strategies, and means for comprehensive studies. A broader picture is thus emerging in which mycoplasmas are successful pathogens having evolved a number of mechanisms and strategies for surviving hostile environments and adapting to new niches or hosts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tick microbiome: the force within

PubMed Central

Narasimhan, Sukanya; Fikrig, Erol

2015-01-01

Ticks are obligate blood-feeders and serve as vectors of human and livestock pathogens worldwide. Defining the tick microbiome and deciphering the interactions between the tick and its symbiotic bacteria in the context of tick development and pathogen transmission, will likely reveal new insights and spawn new paradigms to control tick-borne diseases. Descriptive observations on the tick microbiome that began almost a century ago serve as forerunners to the gathering momentum to define the tick microbiome in greater detail. This review will focus on the current efforts to address the microbiomes of diverse ticks, and the evolving understanding of tick microbiomes. There is hope that these efforts will bring a holistic understanding of pathogen transmission by ticks. PMID:25936226

Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster.

PubMed

Smith, Kelly D

2007-01-01

The host innate immune defense protein lipocalin 2 binds bacterial enterobactin siderophores to limit bacterial iron acquisition. To counteract this host defense mechanism bacteria have acquired the iroA gene cluster, which encodes enzymatic machinery and transporters that revitalize enterobactin in the form of salmochelin. The iroB enzyme introduces glucosyl residues at the C5 site on 2,3-dihydroxybenzoylserine moieties of enterobactin and thereby prevents lipocalin 2 binding. Additional strategies to evade lipocalin 2 have evolved in other bacteria, such as Mycobacteria tuberculosis and Bacillus anthracis. Targeting these specialized bacterial evasion strategy may provide a mechanism to reinvigorate lipocalin 2 in defense against specific pathogens.

2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

PubMed Central

Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

2013-01-01

The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens.

PubMed

Qiu, Tianyi; Yang, Yiyan; Qiu, Jingxuan; Huang, Yang; Xu, Tianlei; Xiao, Han; Wu, Dingfeng; Zhang, Qingchen; Zhou, Chen; Zhang, Xiaoyan; Tang, Kailin; Xu, Jianqing; Cao, Zhiwei

2018-05-02

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.

Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus.

PubMed

Sobel Leonard, Ashley; Weissman, Daniel B; Greenbaum, Benjamin; Ghedin, Elodie; Koelle, Katia

2017-07-15

The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors. IMPORTANCE The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens. Copyright © 2017 Sobel Leonard et al.

[Principles of management in biological infections].

PubMed

Płusa, Tadeusz

2012-11-01

The effectiveness of the management in respiratory infection is depending on the nature of the biological pathogen and the immune status of the patient. For this reason, providing assistance to victims the organ function support, similarly as defining the pathogen and targeted antibiotic therapy should be applied. Available diagnostic tests provide rapid ability to identify the pathogen and antibiotics are able to control infection. Lack of efficacy of treatment may indicate the diversity of the pathogen than previously known and raises suspicion of biological warfare pathogen.

Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission.

PubMed

Ren, Yuwei; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

2017-01-01

Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.

Transport and fate of microbial pathogens in agricultural settings

USGS Publications Warehouse

Bradford, Scott A.; Morales, Veronica L.; Zhang, Wei; Harvey, Ronald W.; Packman, Aaron I.; Mohanram, Arvind; Welty, Claire

2013-01-01

An understanding of the transport and survival of microbial pathogens (pathogens hereafter) in agricultural settings is needed to assess the risk of pathogen contamination to water and food resources, and to develop control strategies and treatment options. However, many knowledge gaps still remain in predicting the fate and transport of pathogens in runoff water, and then through the shallow vadose zone and groundwater. A number of transport pathways, processes, factors, and mathematical models often are needed to describe pathogen fate in agricultural settings. The level of complexity is dramatically enhanced by soil heterogeneity, as well as by temporal variability in temperature, water inputs, and pathogen sources. There is substantial variability in pathogen migration pathways, leading to changes in the dominant processes that control pathogen transport over different spatial and temporal scales. For example, intense rainfall events can generate runoff and preferential flow that can rapidly transport pathogens. Pathogens that survive for extended periods of time have a greatly enhanced probability of remaining viable when subjected to such rapid-transport events. Conversely, in dry seasons, pathogen transport depends more strongly on retention at diverse environmental surfaces controlled by a multitude of coupled physical, chemical, and microbiological factors. These interactions are incompletely characterized, leading to a lack of consensus on the proper mathematical framework to model pathogen transport even at the column scale. In addition, little is known about how to quantify transport and survival parameters at the scale of agricultural fields or watersheds. This review summarizes current conceptual and quantitative models for pathogen transport and fate in agricultural settings over a wide range of spatial and temporal scales. The authors also discuss the benefits that can be realized by improved modeling, and potential treatments to mitigate the risk of waterborne disease transmission.

Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens

PubMed Central

Paillot, Romain; Steward, Karen F.; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C.; Holroyd, Nancy E.; Mungall, Karen; Quail, Michael A.; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M.; Spratt, Brian G.; Jolley, Keith A.; Maiden, Martin C. J.; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D.; Robinson, Carl; Maskell, Duncan J.; Parkhill, Julian; Waller, Andrew S.

2009-01-01

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci. PMID:19325880

Limiting damage during infection: lessons from infection tolerance for novel therapeutics.

PubMed

Vale, Pedro F; Fenton, Andy; Brown, Sam P

2014-01-01

The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (‘‘damage limitation’’)rather than reducing pathogen burdens directly (‘‘pathogen elimination’’). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue,we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ‘‘evolution-proof’’ anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination.

Transient virulence of emerging pathogens.

PubMed

Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

2010-05-06

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

Transient virulence of emerging pathogens

PubMed Central

Bolker, Benjamin M.; Nanda, Arjun; Shah, Dharmini

2010-01-01

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution. PMID:19864267

Plant-bacterial pathogen interactions mediated by type III effectors.

PubMed

Feng, Feng; Zhou, Jian-Min

2012-08-01

Effectors secreted by the bacterial type III system play a central role in the interaction between Gram-negative bacterial pathogens and their host plants. Recent advances in the effector studies have helped cementing several key concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co-evolution. Type III effectors use a variety of biochemical mechanisms to target specific host proteins or DNA for pathogenesis. The identifications of their host targets led to the identification of novel components of plant innate immune system. Key modules of plant immune signaling pathways such as immune receptor complexes and MAPK cascades have emerged as a major battle ground for host-pathogen adaptation. These modules are attacked by multiple type III effectors, and some components of these modules have evolved to actively sense the effectors and trigger immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Amperometric biosensor based on a single antibody of dual function for rapid detection of Streptococcus agalactiae.

PubMed

Vásquez, Gersson; Rey, Alba; Rivera, Camilo; Iregui, Carlos; Orozco, Jahir

2017-01-15

Pathogenic bacteria are responsible for several diseases in humans and in a variety of hosts. Detection of pathogenic bacteria is imperative to avoid and/or fight their potential harmful effects. This work reports on the first amperometric biosensor for the rapid detection of Streptococcus agalactiae (S. agalactiae). The biosensor relies on a single biotinylated antibody that immobilizes the bacteria on a screen-printed carbon electrode while is further linked to a streptavidin-conjugated HRP reporter. The biotinylated antibody provides selectivity to the biosensor whereas serves as an anchoring point to the reporter for further amplification of the electrochemical signal. The resultant immunosensor is simple, responds rapidly, and allows for the selective and highly sensitive quantification of S. agalactiae cells in a concentration range of 10 1 -10 7 CFUml -1 , with a detection limit of 10CFUml -1 . The approach not only enables a rapid detection and quantification of S. agalactiae in environmental samples but also opens up new opportunities for the simple fabrication of electrochemical immunosensors for different target pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental Noise, Genetic Diversity and the Evolution of Evolvability and Robustness in Model Gene Networks

PubMed Central

Steiner, Christopher F.

2012-01-01

The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or “evolvability”) can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise) compared to populations in stable or randomly varying (white noise) environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions. PMID:23284934

Pathogen webs in collapsing honey bee colonies.

PubMed

Cornman, R Scott; Tarpy, David R; Chen, Yanping; Jeffreys, Lacey; Lopez, Dawn; Pettis, Jeffery S; vanEngelsdorp, Dennis; Evans, Jay D

2012-01-01

Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD), otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV) and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees.

Innate cell communication kick-starts pathogen-specific immunity

PubMed Central

Rivera, Amariliz; Siracusa, Mark C.; Yap, George S.; Gause, William C.

2016-01-01

Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of ‘trained’ innate cells that facilitate the rapid elimination of homologous or heterologous infections. PMID:27002843

Rapid detection of foodborne microorganisms on food surface using Fourier transform Raman spectroscopy

NASA Astrophysics Data System (ADS)

Yang, Hong; Irudayaraj, Joseph

2003-02-01

Fourier transform (FT) Raman spectroscopy was used for non-destructive characterization and differentiation of six different microorganisms including the pathogen Escherichia coli O157:H7 on whole apples. Mahalanobis distance metric was used to evaluate and quantify the statistical differences between the spectra of six different microorganisms. The same procedure was extended to discriminate six different strains of E. coli. The FT-Raman procedure was not only successful in discriminating the different E. coli strain but also accurately differentiated the pathogen from non-pathogens. Results demonstrate that FT-Raman spectroscopy can be an excellent tool for rapid examination of food surfaces for microorganism contamination and for the classification of microbial cultures.

Evaluation of high-resolution melting curve analysis of ligation-mediated real-time PCR, a rapid method for epidemiological typing of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter Species) pathogens.

PubMed

Woksepp, Hanna; Ryberg, Anna; Billström, Hanna; Hällgren, Anita; Nilsson, Lennart E; Marklund, Britt-Inger; Olsson-Liljequist, Barbro; Schön, Thomas

2014-12-01

A single-tube method, ligation-mediated real-time PCR high-resolution melt analysis (LMqPCR HRMA), was modified for the rapid typing of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens. A 97% agreement (60/62 isolates) was achieved in comparison to pulsed-field gel electrophoresis (PFGE) results, which indicates that LMqPCR HRMA is a rapid and accurate screening tool for monitoring nosocomial outbreaks. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Molecular evolution of an Avirulence Homolog (Avh) gene subfamily in Phytophthora ramorum

Treesearch

GossErica M.; Caroline M. Press; Niklaus J. Grünwald

2008-01-01

Pathogen effectors can serve a virulence function on behalf of the pathogen or trigger a rapid defense response in resistant hosts. Sequencing of the Phytophthora ramorum genome and subsequent analysis identified a diverse superfamily of approximately 350 genes that are homologous to the four known avirulence genes in plant pathogenic oomycetes and...

Strain-Level Metagenomic Analysis of the Fermented Dairy Beverage Nunu Highlights Potential Food Safety Risks

PubMed Central

Walsh, Aaron M.; Crispie, Fiona; Daari, Kareem; O'Sullivan, Orla; Martin, Jennifer C.; Arthur, Cornelius T.; Claesson, Marcus J.; Scott, Karen P.

2017-01-01

ABSTRACT The rapid detection of pathogenic strains in food products is essential for the prevention of disease outbreaks. It has already been demonstrated that whole-metagenome shotgun sequencing can be used to detect pathogens in food but, until recently, strain-level detection of pathogens has relied on whole-metagenome assembly, which is a computationally demanding process. Here we demonstrated that three short-read-alignment-based methods, i.e., MetaMLST, PanPhlAn, and StrainPhlAn, could accurately and rapidly identify pathogenic strains in spinach metagenomes that had been intentionally spiked with Shiga toxin-producing Escherichia coli in a previous study. Subsequently, we employed the methods, in combination with other metagenomics approaches, to assess the safety of nunu, a traditional Ghanaian fermented milk product that is produced by the spontaneous fermentation of raw cow milk. We showed that nunu samples were frequently contaminated with bacteria associated with the bovine gut and, worryingly, we detected putatively pathogenic E. coli and Klebsiella pneumoniae strains in a subset of nunu samples. Ultimately, our work establishes that short-read-alignment-based bioinformatics approaches are suitable food safety tools, and we describe a real-life example of their utilization. IMPORTANCE Foodborne pathogens are responsible for millions of illnesses each year. Here we demonstrate that short-read-alignment-based bioinformatics tools can accurately and rapidly detect pathogenic strains in food products by using shotgun metagenomics data. The methods used here are considerably faster than both traditional culturing methods and alternative bioinformatics approaches that rely on metagenome assembly; therefore, they can potentially be used for more high-throughput food safety testing. Overall, our results suggest that whole-metagenome sequencing can be used as a practical food safety tool to prevent diseases or to link outbreaks to specific food products. PMID:28625983

Rapidly rotating single late-type giants: New FK Comae stars?

NASA Technical Reports Server (NTRS)

Fekel, Francis C.

1986-01-01

A group of rapidly rotating single late-type giants was found from surveys of chromospherically active stars. These stars have V sin I's ranging from 6 to 46 km/sec, modest ultraviolet emission line fluxes, and strong H alpha absorption lines. Although certainly chromospherically active, their characteristics are much less extreme than those of FK Com and one or two other similar systems. One possible explanation for the newly identified systems is that they have evolved from stars similar to FK Com. The chromospheric activity and rotation of single giant stars like FK Com would be expected to decrease with time as they do in single dwarfs. Alternatively, this newly identified group may have evolved from single rapidly rotating A, or early F stars.

Insects as alternative hosts for phytopathogenic bacteria.

PubMed

Nadarasah, Geetanchaly; Stavrinides, John

2011-05-01

Phytopathogens have evolved specialized pathogenicity determinants that enable them to colonize their specific plant hosts and cause disease, but their intimate associations with plants also predispose them to frequent encounters with herbivorous insects, providing these phytopathogens with ample opportunity to colonize and eventually evolve alternative associations with insects. Decades of research have revealed that these associations have resulted in the formation of bacterial-vector relationships, in which the insect mediates dissemination of the plant pathogen. Emerging research, however, has highlighted the ability of plant pathogenic bacteria to use insects as alternative hosts, exploiting them as they would their primary plant host. The identification of specific bacterial genetic determinants that mediate the interaction between bacterium and insect suggests that these interactions are not incidental, but have likely arisen following the repeated association of microorganisms with particular insects over evolutionary time. This review will address the biology and ecology of phytopathogenic bacteria that interact with insects, including the traditional role of insects as vectors, as well as the newly emerging paradigm of insects serving as alternative primary hosts. Also discussed is one case where an insect serves as both host and vector, which may represent a transitionary stage in the evolution of insect-phytopathogen associations. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

PubMed

Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

2011-09-01

The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

Cationized Magnetoferritin Enables Rapid Labeling and Concentration of Gram-Positive and Gram-Negative Bacteria in Magnetic Cell Separation Columns

PubMed Central

Spencer, J.; Schwarzacher, W.

2016-01-01

ABSTRACT In order to identify pathogens rapidly and reliably, bacterial capture and concentration from large sample volumes into smaller ones are often required. Magnetic labeling and capture of bacteria using a magnetic field hold great promise for achieving this goal, but the current protocols have poor capture efficiency. Here, we present a rapid and highly efficient approach to magnetic labeling and capture of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria using cationized magnetoferritin (cat-MF). Magnetic labeling was achieved within a 1-min incubation period with cat-MF, and 99.97% of the labeled bacteria were immobilized in commercially available magnetic cell separation (MACS) columns. Longer incubation times led to more efficient capture, with S. aureus being immobilized to a greater extent than E. coli. Finally, low numbers of magnetically labeled E. coli bacteria (<100 CFU per ml) were immobilized with 100% efficiency and concentrated 7-fold within 15 min. Therefore, our study provides a novel protocol for rapid and highly efficient magnetic labeling, capture, and concentration of both Gram-positive and Gram-negative bacteria. IMPORTANCE Antimicrobial resistance (AMR) is a significant global challenge. Rapid identification of pathogens will retard the spread of AMR by enabling targeted treatment with suitable agents and by reducing inappropriate antimicrobial use. Rapid detection methods based on microfluidic devices require that bacteria are concentrated from large volumes into much smaller ones. Concentration of bacteria is also important to detect low numbers of pathogens with confidence. Here, we demonstrate that magnetic separation columns capture small amounts of bacteria with 100% efficiency. Rapid magnetization was achieved by exposing bacteria to cationic magnetic nanoparticles, and magnetized bacteria were concentrated 7-fold inside the column. Thus, bacterial capture and concentration were achieved within 15 min. This approach could be extended to encompass the capture and concentration of specific pathogens, for example, by functionalizing magnetic nanoparticles with antibodies or small molecule probes. PMID:27060124

Cationized Magnetoferritin Enables Rapid Labeling and Concentration of Gram-Positive and Gram-Negative Bacteria in Magnetic Cell Separation Columns.

PubMed

Correia Carreira, S; Spencer, J; Schwarzacher, W; Seddon, A M

2016-06-15

In order to identify pathogens rapidly and reliably, bacterial capture and concentration from large sample volumes into smaller ones are often required. Magnetic labeling and capture of bacteria using a magnetic field hold great promise for achieving this goal, but the current protocols have poor capture efficiency. Here, we present a rapid and highly efficient approach to magnetic labeling and capture of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria using cationized magnetoferritin (cat-MF). Magnetic labeling was achieved within a 1-min incubation period with cat-MF, and 99.97% of the labeled bacteria were immobilized in commercially available magnetic cell separation (MACS) columns. Longer incubation times led to more efficient capture, with S. aureus being immobilized to a greater extent than E. coli Finally, low numbers of magnetically labeled E. coli bacteria (<100 CFU per ml) were immobilized with 100% efficiency and concentrated 7-fold within 15 min. Therefore, our study provides a novel protocol for rapid and highly efficient magnetic labeling, capture, and concentration of both Gram-positive and Gram-negative bacteria. Antimicrobial resistance (AMR) is a significant global challenge. Rapid identification of pathogens will retard the spread of AMR by enabling targeted treatment with suitable agents and by reducing inappropriate antimicrobial use. Rapid detection methods based on microfluidic devices require that bacteria are concentrated from large volumes into much smaller ones. Concentration of bacteria is also important to detect low numbers of pathogens with confidence. Here, we demonstrate that magnetic separation columns capture small amounts of bacteria with 100% efficiency. Rapid magnetization was achieved by exposing bacteria to cationic magnetic nanoparticles, and magnetized bacteria were concentrated 7-fold inside the column. Thus, bacterial capture and concentration were achieved within 15 min. This approach could be extended to encompass the capture and concentration of specific pathogens, for example, by functionalizing magnetic nanoparticles with antibodies or small molecule probes. Copyright © 2016 Correia Carreira et al.

Discovery and characterization of a novel plant pathogen protease

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins are fungal proteases that attack specific plant defense chitinases. At least three unrelated types of proteases have evolved to have this function. They all truncate the targeted chitinases by cleaving near their amino termini, but each protease type targets a different ...

Carbohydrates, proteins, cell surfaces, and the biochemistry of pathogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albersheim, P.; Anderson-Prouty, A.J.

1975-01-01

General plant resistance to pathogenic attack by a myriad of microorganisms, viruses, nematodes, and insects are reviewed. Specifically discussed are: The role of the cell wall and wall-degrading enzymes in infective processes; an hypothesis to account for varietal specificity in gene-for-gene host-pathogen systems; examples which demonstrate that cell surface recognition phenomena are mediated through the interaction of carbohydrate-containing macromolecules and proteins; elicitors of phytoalexin production; and further consideration of the hypothesis and how the gene-for-gene relationship may have evolved. (JWP)

Antifungal activity in thrips soldiers suggests a dual role for this caste.

PubMed

Turnbull, Christine; Caravan, Holly; Chapman, Thomas; Nipperess, David; Dennison, Siobhan; Schwarz, Michael; Beattie, Andrew

2012-08-23

The social insect soldier is perhaps the most widely known caste, because it often exhibits spectacular weapons, such as highly enlarged jaws or reinforced appendages, which are used to defend the colony against enemies ranging in size from wasps to anteaters. We examined the function of the enlarged forelimbs of soldiers (both male and female) of the eusocial, gall-inhabiting insect Kladothrips intermedius, and discovered that they have little impact on their ability to repel the specialized invading thrips Koptothrips species. While the efficacy of the enlarged forelimb appears equivocal, we show that soldiers secrete strong antifungal compounds capable of controlling the specialized insect fungal pathogen, Cordyceps bassiana. Our data suggest that these thrips soldiers have evolved in response to selection by both macro- and micro-organisms. While it is unknown whether specialized fungal pathogens have been major selective agents in the evolution of the soldier caste in general, they were probably present when sociality first evolved and may have been the primordial enemies of social insects.

Population genomics reveals the origin and asexual evolution of human infective trypanosomes

PubMed Central

Weir, William; Capewell, Paul; Foth, Bernardo; Clucas, Caroline; Pountain, Andrew; Steketee, Pieter; Veitch, Nicola; Koffi, Mathurin; De Meeûs, Thierry; Kaboré, Jacques; Camara, Mamadou; Cooper, Anneli; Tait, Andy; Jamonneau, Vincent; Bucheton, Bruno; Berriman, Matt; MacLeod, Annette

2016-01-01

Evolutionary theory predicts that the lack of recombination and chromosomal re-assortment in strictly asexual organisms results in homologous chromosomes irreversibly accumulating mutations and thus evolving independently of each other, a phenomenon termed the Meselson effect. We apply a population genomics approach to examine this effect in an important human pathogen, Trypanosoma brucei gambiense. We determine that T.b. gambiense is evolving strictly asexually and is derived from a single progenitor, which emerged within the last 10,000 years. We demonstrate the Meselson effect for the first time at the genome-wide level in any organism and show large regions of loss of heterozygosity, which we hypothesise to be a short-term compensatory mechanism for counteracting deleterious mutations. Our study sheds new light on the genomic and evolutionary consequences of strict asexuality, which this pathogen uses as it exploits a new biological niche, the human population. DOI: http://dx.doi.org/10.7554/eLife.11473.001 PMID:26809473

Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria.

PubMed

Fuzi, Miklos; Szabo, Dora; Csercsik, Rita

2017-01-01

The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated.

Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria

PubMed Central

Fuzi, Miklos; Szabo, Dora; Csercsik, Rita

2017-01-01

The major international sequence types/lineages of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and ESBL-producing E. coli were demonstrated to have been advanced by favorable fitness balance associated with high-level resistance to fluoroquinolones. The paper shows that favorable fitness in the major STs/lineages of these pathogens was principally attained by the capacity of evolving mutations in the fluoroquinolone-binding serine residues of both the DNA gyrase and topoisomerase IV enzymes. The available information on fitness balance incurred by individual and various combinations of mutations in the enzymes is reviewed in multiple species. Moreover, strong circumstantial evidence is presented that major STs/lineages of other multi-drug resistant bacteria, primarily vancomycin-resistant Enterococcus faecium (VRE), emerged by a similar mechanism. The reason(s) why the major ST/lineage strains of various pathogens proved more adept at evolving favorable mutations than most isolates of the same species remains to be elucidated. PMID:29250038

Making your skin crawl: The role of tactile sensitivity in disease avoidance.

PubMed

Hunt, David Francis; Cannell, Grace; Davenhill, Nicholas A; Horsford, Stephanie A; Fleischman, Diana S; Park, Justin H

2017-07-01

Mounting evidence indicates that animals, including humans, have evolved a behavioral disease-avoidance system designed to facilitate the detection and avoidance of sources of pathogens, and that this system interacts with physiological defenses. The skin acts as an important anatomical barrier, yet little research has investigated the role of tactile sensitivity in disease avoidance. Increased tactile sensitivity in the presence of potential sources of pathogens may facilitate prophylactic behaviors such as self-grooming. Across multiple studies, we tested the hypothesis that the induction of disgust-the key emotion underlying disease avoidance-may lead to greater tactile sensitivity compared to control conditions. A nonsignificant trend was found in a pilot study, which was replicated (and found to be significant) in Studies 1 and 2. To our knowledge, these results are the first to demonstrate disgust-induced changes in tactile sensitivity, and they contribute to the growing literature on the integrated evolved defenses against infectious disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Plates and Mantle Convection: A Far-From Equilibrium Self-Organized System

NASA Astrophysics Data System (ADS)

King, S. D.; Lowman, J. P.; Gable, C. W.

2001-12-01

A common observation of plate tectonics is that plate velocities change over short time scales. Some have speculated that these reorganization events are triggered by evolving plate boundaries. This work presents an alternative mechanism, due to the interaction of mobil plates and internally heated convection. We present numerical models of 3D Cartesian convection in an internally-heated fluid with mobile plates that exhibit rapid changes in plate motion. A persistent feature of these calculations is that plate motion is relatively uniform punctuated by rapid reorganization events where plate speed and direction change over a short time period. The rapid changes in plate motion result solely from the interaction of internally-heated convection and the mobile plates. Without plates, the convective planform of an internally-heated fluid evolves into a pattern with a larger number of small cells. When plates are included, the fluid is dominated by plate-scale structures; however, isolated regions develop where heat builds up. These isolated regions are near the location of mature slabs where the plates are older and thicker. As the system evolves, the temperature (and buoyancy) in these isolated regions increases, they become unstable and, as they rise, the net force on the plate is no longer dominated by `slab pull' from the mature slab. The plate reorganization allows the system to transfer heat from the short-wavelength, internal-heating scale, to the longer-wavelength, plate-cooling scale. As we will demonstrate, the interaction between plate motions and the mantle is sufficiently dynamic that evolving plate boundaries are not necessary to achieve rapid changes in plate motion.

Recent advances in rapid pathogen detection method based on biosensors.

PubMed

Chen, Ying; Wang, Zhenzhen; Liu, Yingxun; Wang, Xin; Li, Ying; Ma, Ping; Gu, Bing; Li, Hongchun

2018-06-01

As strain variation and drug resistance become more pervasive, the prevention and control of infection have been a serious problem in recent years. The detection of pathogen is one of the most important parts of the process of diagnosis. Having a series of advantages, such as rapid response, high sensitivity, ease of use, and low cost, biosensors have received much attention and been studied deeply. Moreover, relying on its characteristics of small size, real time, and multiple analyses, biosensors have developed rapidly and used widely and are expected to be applied for microbiological detection in order to meet higher accuracy required by clinical diagnosis. The main goal of this contribution is not to simply collect and list all papers related to pathogen detection based on biosensors published recently, but to discuss critically the development and application of many kinds of biosensors such as electrochemical (amperometric, impedimetric, potentiometric, and conductometric), optical (fluorescent, fibre optic and surface plasmon resonance), and piezoelectric (quartz crystal microbalances and atomic force microscopy) biosensors in pathogen detection as well as the comparisons with the existing clinical detection methods (traditional culture, enzyme-linked immunosorbent assay, polymerase chain reaction, and mass spectrometry).

Identification of urinary tract pathogens after 3-hours urine culture by MALDI-TOF mass spectrometry.

PubMed

Haiko, Johanna; Savolainen, Laura E; Hilla, Risto; Pätäri-Sampo, Anu

2016-10-01

Complicated urinary tract infections, such as pyelonephritis, may lead to sepsis. Rapid diagnosis is needed to identify the causative urinary pathogen and to verify the appropriate empirical antimicrobial therapy. We describe here a rapid identification method for urinary pathogens: urine is incubated on chocolate agar for 3h at 35°C with 5% CO2 and subjected to MALDI-TOF MS analysis by VITEK MS. Overall 207 screened clinical urine samples were tested in parallel with conventional urine culture. The method, called U-si-MALDI-TOF (urine short incubation MALDI-TOF), showed correct identification for 86% of Gram-negative urinary tract pathogens (Escherichia coli, Klebsiella pneumoniae, and other Enterobacteriaceae), when present at >10(5)cfu/ml in culture (n=107), compared with conventional culture method. However, Gram-positive bacteria (n=28) were not successfully identified by U-si-MALDI-TOF. This method is especially suitable for rapid identification of E. coli, the most common cause of urinary tract infections and urosepsis. Turnaround time for identification using U-si-MALDI-TOF compared with conventional urine culture was improved from 24h to 4-6h. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid and field-deployable biological and chemical Raman-based identification

NASA Astrophysics Data System (ADS)

Botonjic-Sehic, Edita; Paxon, Tracy L.; Boudries, Hacene

2011-06-01

Pathogen detection using Raman spectroscopy is achieved through the use of a sandwich immunoassay. Antibody-modified magnetic beads are used to capture and concentrate target analytes in solution and surface-enhanced Raman spectroscopy (SERS) tags are conjugated with antibodies and act as labels to enable specific detection of biological pathogens. The rapid detection of biological pathogens is critical to first responders, thus assays to detect E.Coli and Anthrax have been developed and will be reported. The problems associated with pathogen detection resulting from the spectral complexity and variability of microorganisms are overcome through the use of SERS tags, which provide an intense, easily recognizable, and spectrally consistent Raman signal. The developed E. coli assay has been tested with 5 strains of E. coli and shows a low limit of detection, on the order of 10 and 100 c.f.u. per assay. Additionally, the SERS assay utilizes magnetic beads to collect the labeled pathogens into the focal point of the detection laser beam, making the assay robust to commonly encountered white powder interferants such as flour, baking powder, and corn starch. The reagents were also found to be stable at room temperature over extended periods of time with testing conducted over a one year period. Finally, through a specialized software algorithm, the assays are interfaced to the Raman instrument, StreetLab Mobile, for rapid-field-deployable biological identification.

Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node.

PubMed

Chtanova, Tatyana; Han, Seong-Ji; Schaeffer, Marie; van Dooren, Giel G; Herzmark, Paul; Striepen, Boris; Robey, Ellen A

2009-08-21

Memory T cells circulate through lymph nodes where they are poised to respond rapidly upon re-exposure to a pathogen; however, the dynamics of memory T cell, antigen-presenting cell, and pathogen interactions during recall responses are largely unknown. We used a mouse model of infection with the intracellular protozoan parasite, Toxoplasma gondii, in conjunction with two-photon microscopy, to address this question. After challenge, memory T cells migrated more rapidly than naive T cells, relocalized toward the subcapsular sinus (SCS) near invaded macrophages, and engaged in prolonged interactions with infected cells. Parasite invasion of T cells occurred by direct transfer of the parasite from the target cell into the T cell and corresponded to an antigen-specific increase in the rate of T cell invasion. Our results provide insight into cellular interactions during recall responses and suggest a mechanism of pathogen subversion of the immune response.

Real-Time Continuous Identification of Greenhouse Plant Pathogens Based on Recyclable Microfluidic Bioassay System.

PubMed

Qu, Xiangmeng; Li, Min; Zhang, Hongbo; Lin, Chenglie; Wang, Fei; Xiao, Mingshu; Zhou, Yi; Shi, Jiye; Aldalbahi, Ali; Pei, Hao; Chen, Hong; Li, Li

2017-09-20

The development of a real-time continuous analytical platform for the pathogen detection is of great scientific importance for achieving better disease control and prevention. In this work, we report a rapid and recyclable microfluidic bioassay system constructed from oligonucleotide arrays for selective and sensitive continuous identification of DNA targets of fungal pathogens. We employ the thermal denaturation method to effectively regenerate the oligonucleotide arrays for multiple sample detection, which could considerably reduce the screening effort and costs. The combination of thermal denaturation and laser-induced fluorescence detection technique enables real-time continuous identification of multiple samples (<10 min per sample). As a proof of concept, we have demonstrated that two DNA targets of fungal pathogens (Botrytis cinerea and Didymella bryoniae) can be sequentially analyzed using our rapid microfluidic bioassay system, which provides a new paradigm in the design of microfluidic bioassay system and will be valuable for chemical and biomedical analysis.

Osmoregulatory physiology and rapid evolution of salinity tolerance in threespine stickleback recently introduced to fresh water

USGS Publications Warehouse

Divino, Jeffrey N; Monette, Michelle Y.; McCormick, Stephen; Yancey, Paul H.; Flannery, Kyle G.; Bell, Michael A.; Rollins, Jennifer L.; von Hippel, Frank A.; Schultz, Eric T.

2016-01-01

Conclusion: Enhanced freshwater tolerance has evolved rapidly in recently landlocked stickleback compared with their anadromous ancestors (0.569 haldanes), but the former have retained ancestral seawater-osmoregulatory function.

RAPIDLY ROTATING, X-RAY BRIGHT STARS IN THE KEPLER FIELD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howell, Steve B.; Mason, Elena; Boyd, Patricia

We present Kepler light curves and optical spectroscopy of twenty X-ray bright stars located in the Kepler field of view. The stars, spectral type F-K, show evidence for rapid rotation including chromospheric activity 100 times or more above the Sun at maximum and flaring behavior in their light curves. Eighteen of our objects appear to be (sub)giants and may belong to the class of FK Com variables, which are evolved rapidly spinning single stars with no excretion disk and high levels of chromospheric activity. Such stars are rare and are likely the result of W UMa binary mergers, a processmore » believed to produce the FK Com class of variable and their descendants. The FK Com stage, including the presence of an excretion disk, is short lived but leads to longer-lived stages consisting of single, rapidly rotating evolved (sub)giants with high levels of stellar activity.« less

Rapidly Rotating, X-Ray Bright Stars in the Kepler Field

NASA Technical Reports Server (NTRS)

Howell, Steve B.; Mason, Elena; Boyd, Patricia; Smith, Krista Lynne; Gelino, Dawn M.

2016-01-01

We present Kepler light curves and optical spectroscopy of twenty X-ray bright stars located in the Kepler field of view. The stars, spectral type F-K, show evidence for rapid rotation including chromospheric activity 100 times or more above the Sun at maximum and flaring behavior in their light curves. Eighteen of our objects appear to be (sub)giants and may belong to the class of FK Com variables, which are evolved rapidly spinning single stars with no excretion disk and high levels of chromospheric activity. Such stars are rare and are likely the result of W UMa binary mergers, a process believed to produce the FK Com class of variable and their descendants. The FK Com stage, including the presence of an excretion disk, is short lived but leads to longer-lived stages consisting of single, rapidly rotating evolved (sub)giants with high levels of stellar activity.

Evolutionary suicide through a non-catastrophic bifurcation: adaptive dynamics of pathogens with frequency-dependent transmission.

PubMed

Boldin, Barbara; Kisdi, Éva

2016-03-01

Evolutionary suicide is a riveting phenomenon in which adaptive evolution drives a viable population to extinction. Gyllenberg and Parvinen (Bull Math Biol 63(5):981-993, 2001) showed that, in a wide class of deterministic population models, a discontinuous transition to extinction is a necessary condition for evolutionary suicide. An implicit assumption of their proof is that the invasion fitness of a rare strategy is well-defined also in the extinction state of the population. Epidemic models with frequency-dependent incidence, which are often used to model the spread of sexually transmitted infections or the dynamics of infectious diseases within herds, violate this assumption. In these models, evolutionary suicide can occur through a non-catastrophic bifurcation whereby pathogen adaptation leads to a continuous decline of host (and consequently pathogen) population size to zero. Evolutionary suicide of pathogens with frequency-dependent transmission can occur in two ways, with pathogen strains evolving either higher or lower virulence.

Immune subversion by chromatin manipulation: a 'new face' of host-bacterial pathogen interaction.

PubMed

Arbibe, Laurence

2008-08-01

Bacterial pathogens have evolved various strategies to avoid immune surveillance, depending of their in vivo'lifestyle'. The identification of few bacterial effectors capable to enter the nucleus and modifying chromatin structure in host raises the fascinating questions of how pathogens modulate chromatin structure and why. Chromatin is a dynamic structure that maintains the stability and accessibility of the host DNA genome to the transcription machinery. This review describes the various strategies used by pathogens to interface with host chromatin. In some cases, chromatin injury can be a strategy to take control of major cellular functions, such as the cell cycle. In other cases, manipulation of chromatin structure at specific genomic locations by modulating epigenetic information provides a way for the pathogen to impose its own transcriptional signature onto host cells. This emerging field should strongly influence our understanding of chromatin regulation at interphase nucleus and may provide invaluable openings to the control of immune gene expression in inflammatory and infectious diseases.

Institutions, Parasites and the Persistence of In-group Preferences

PubMed Central

Hruschka, Daniel J.; Henrich, Joseph

2013-01-01

Much research has established reliable cross-population differences in motivations to invest in one’s in-group. We compare two current historical-evolutionary hypotheses for this variation based on (1) effective large-scale institutions and (2) pathogen threats by analyzing cross-national differences (N = 122) in in-group preferences measured in three ways. We find that the effectiveness of government institutions correlates with favoring in-group members, even when controlling for pathogen stress and world region, assessing reverse causality, and providing a check on endogeneity with an instrumental variable analysis. Conversely, pathogen stress shows inconsistent associations with in-group favoritism when controlling for government effectiveness. Moreover, pathogen stress shows little to no association with in-group favoritism within major world regions whereas government effectiveness does. These results suggest that variation in in-group preferences across contemporary nation-states is more consistent with a generalized response to institutions that meet basic needs rather than an evolved response dedicated to pathogens. PMID:23704926

Identification of secreted bacterial proteins by noncanonical amino acid tagging

PubMed Central

Mahdavi, Alborz; Szychowski, Janek; Ngo, John T.; Sweredoski, Michael J.; Graham, Robert L. J.; Hess, Sonja; Schneewind, Olaf; Mazmanian, Sarkis K.; Tirrell, David A.

2014-01-01

Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation of azidonorleucine (Anl), a methionine surrogate that requires a mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched by affinity purification. Application of the method to analysis of the type III secretion system of the human pathogen Yersinia enterocolitica enabled efficient identification of secreted proteins, identification of distinct secretion profiles for intracellular and extracellular bacteria, and determination of the order of substrate injection into host cells. This approach should be widely useful for the identification of virulence factors in microbial pathogens and the development of potential new targets for antimicrobial therapy. PMID:24347637

Botrytis cinerea Manipulates the Antagonistic Effects between Immune Pathways to Promote Disease Development in Tomato[C][W][OA

PubMed Central

El Oirdi, Mohamed; El Rahman, Taha Abd; Rigano, Luciano; El Hadrami, Abdelbasset; Rodriguez, María Cecilia; Daayf, Fouad; Vojnov, Adrian; Bouarab, Kamal

2011-01-01

Plants have evolved sophisticated mechanisms to sense and respond to pathogen attacks. Resistance against necrotrophic pathogens generally requires the activation of the jasmonic acid (JA) signaling pathway, whereas the salicylic acid (SA) signaling pathway is mainly activated against biotrophic pathogens. SA can antagonize JA signaling and vice versa. Here, we report that the necrotrophic pathogen Botrytis cinerea exploits this antagonism as a strategy to cause disease development. We show that B. cinerea produces an exopolysaccharide, which acts as an elicitor of the SA pathway. In turn, the SA pathway antagonizes the JA signaling pathway, thereby allowing the fungus to develop its disease in tomato (Solanum lycopersicum). SA-promoted disease development occurs through Nonexpressed Pathogen Related1. We also show that the JA signaling pathway required for tomato resistance against B. cinerea is mediated by the systemin elicitor. These data highlight a new strategy used by B. cinerea to overcome the plant’s defense system and to spread within the host. PMID:21665999

Parasitic, fungal and prion zoonoses: an expanding universe of candidates for human disease.

PubMed

Akritidis, N

2011-03-01

Zoonotic infections have emerged as a burden for millions of people in recent years, owing to re-emerging or novel pathogens often causing outbreaks in the developing world in the presence of inadequate public health infrastructure. Among zoonotic infections, those caused by parasitic pathogens are the ones that affect millions of humans worldwide, who are also at risk of developing chronic disease. The present review discusses the global effect of protozoan pathogens such as Leishmania sp., Trypanosoma sp., and Toxoplasma sp., as well as helminthic pathogens such as Echinococcus sp., Fasciola sp., and Trichinella sp. The zoonotic aspects of agents that are not essentially zoonotic are also discussed. The review further focuses on the zoonotic dynamics of fungal pathogens and prion diseases as observed in recent years, in an evolving environment in which novel patient target groups have developed for agents that were previously considered to be obscure or of minimal significance. © 2011 The Author. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

PubMed

Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

2009-03-10

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function

PubMed Central

Osborne, Suzanne E.; Walthers, Don; Tomljenovic, Ana M.; Mulder, David T.; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J.; Wickham, Mark E.; Waller, Ross F.; Kenney, Linda J.; Coombes, Brian K.

2009-01-01

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones. PMID:19234126

DNA aptamers as a novel approach to neutralize Staphylococcus aureus α-toxin.

PubMed

Vivekananda, Jeevalatha; Salgado, Christi; Millenbaugh, Nancy J

2014-02-14

Staphylococcus aureus is a versatile pathogen capable of causing a broad spectrum of diseases ranging from superficial skin infections to life threatening conditions such as endocarditis, septicemia, pneumonia and toxic shock syndrome. In vitro and in vivo studies identified an exotoxin, α-toxin, as a major cause of S. aureus toxicity. Because S. aureus has rapidly evolved resistance to a number of antibiotics, including methicillin, it is important to identify new therapeutic strategies, other than antibiotics, for inhibiting the harmful effects of this pathogen. Aptamers are single-stranded DNA or RNA oligonucleotides with three-dimensional folded conformations that bind with high affinity and selectivity to targets and modulate their biological functions. The goal of this study was to isolate DNA aptamers that specifically inhibit the cytotoxic activity of α-toxin. After 10 rounds of Systematic Evolution of Ligands by EXponential Enrichment (SELEX), 49 potential anti-α-toxin aptamers were identified. In vitro neutralization assays demonstrated that 4 of these 49 aptamers, AT-27, AT-33, AT-36, and AT-49, significantly inhibited α-toxin-mediated cell death in Jurkat T cells. Furthermore, RT-PCR analysis revealed that α-toxin increased the transcription of the inflammatory cytokines TNF-α and IL-17 and that anti-α-toxin aptamers AT-33 and AT-36 inhibited the upregulation of these genes. Collectively, the data suggest the feasibility of generating functionally effective aptamers against α-toxin for treatment of S. aureus infections. Published by Elsevier Inc.

Ironing Out the Unconventional Mechanisms of Iron Acquisition and Gene Regulation in Chlamydia

PubMed Central

Pokorzynski, Nick D.; Thompson, Christopher C.; Carabeo, Rey A.

2017-01-01

The obligate intracellular pathogen Chlamydia trachomatis, along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron in vitro induces an aberrant morphological phenotype termed “persistence.” This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute Chlamydia-associated chronic diseases in susceptible populations. Given the importance of iron to Chlamydia, relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria. Analysis of the genome sequences of a variety of chlamydial species hinted at the involvement of unconventional mechanisms, being that Chlamydia lack many conventional systems of iron homeostasis that are highly conserved in other bacteria. Herein we detail past and current research regarding chlamydial iron biology in an attempt to provide context to the rapid progress of the field in recent years. We aim to highlight recent discoveries and innovations that illuminate the strategies involved in chlamydial iron homeostasis, including the vesicular mode of acquiring iron from the intracellular environment, and the identification of a putative iron-dependent transcriptional regulator that is synthesized as a fusion with a ABC-type transporter subunit. These recent findings, along with the noted absence of iron-related homologs, indicate that Chlamydia have evolved atypical approaches to the problem of iron homeostasis, reinvigorating research into the iron biology of this pathogen. PMID:28951853

White spot syndrome virus (WSSV) genome stability maintained over six passages through three different penaeid shrimp species.

PubMed

Sindhupriya, M; Saravanan, P; Otta, S K; Amarnath, C Bala; Arulraj, R; Bhuvaneswari, T; Praveena, P Ezhil; Jithendran, K P; Ponniah, A G

2014-08-21

White spot syndrome virus (WSSV) replicates rapidly, can be extremely pathogenic and is a common cause of mass mortality in cultured shrimp. Variable number tandem repeat (VNTR) sequences present in the open reading frame (ORF)94, ORF125 and ORF75 regions of the WSSV genome have been used widely as genetic markers in epidemiological studies. However, reports that VNTRs might evolve rapidly following even a single transmission through penaeid shrimp or other crustacean hosts have created confusion as to how VNTR data is interpreted. To examine VNTR stability again, 2 WSSV strains (PmTN4RU and LvAP11RU) with differing ORF94 tandem repeat numbers and slight differences in apparent virulence were passaged sequentially 6 times through black tiger shrimp Penaeus monodon, Indian white shrimp Feneropenaeus indicus or Pacific white leg shrimp Litopenaeus vannamei. PCR analyses to genotype the ORF94, ORF125 and ORF75 VNTRs did not identify any differences from either of the 2 parental WSSV strains after multiple passages through any of the shrimp species. These data were confirmed by sequence analysis and indicate that the stability of the genome regions containing these VNTRs is quite high at least for the WSSV strains, hosts and number of passages examined and that the VNTR sequences thus represent useful genetic markers for studying WSSV epidemiology.

Emerging nanotechnology based strategies for diagnosis and therapeutics of urinary tract infections: A review.

PubMed

Kumar, M S; Das, A P

2017-11-01

At present, various diagnostic and therapeutic approaches are available for urinary tract infections. But, still the quest for development of more rapid, accurate and reliable approach is an unending process. The pathogens, especially uropathogens are adapting to new environments and antibiotics day by day rapidly. Therefore, urinary tract infections are evolving as hectic and difficult to eradicate, increasing the economic burden to the society. The technological advances should be able to compete the adaptability characteristics of microorganisms to combat their growth in new environments and thereby preventing their infections. Nanotechnology is at present an extensively developing area of immense scientific interest since it has diverse potential applications in biomedical field. Nanotechnology may be combined with cellular therapy approaches to overcome the limitations caused by conventional therapeutics. Nanoantibiotics and drug delivery using nanotechnology are currently growing areas of research in biomedical field. Recently, various categories of antibacterial nanoparticles and nanocarriers for drug delivery have shown their potential in the treatment of infectious diseases. Nanoparticles, compared to conventional antibiotics, are more beneficial in terms of decreasing toxicity, prevailing over resistance and lessening costs. Nanoparticles present long term therapeutic effects since they are retained in body for relatively longer periods. This review focuses on recent advances in the field of nanotechnology, principally emphasizing diagnostics and therapeutics of urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Evolutionary dynamics of interactions between plants and their enemies: comparison of herbivorous insects and pathogens.

PubMed

Wininger, Kerry; Rank, Nathan

2017-11-01

Plants colonized land over 400 million years ago. Shortly thereafter, organisms began to consume terrestrial plant tissue as a nutritional resource. Most plant enemies are plant pathogens or herbivores, and they impose natural selection for plants to evolve defenses. These traits generate selection pressures on enemies. Coevolution between terrestrial plants and their enemies is an important element of the evolutionary history of both groups. However, coevolutionary studies of plant-pathogen interactions have tended to focus on different research topics than plant-herbivore interactions. Specifically, studies of plant-pathogen interactions often adopt a "gene-for-gene" conceptual framework. In contrast, studies of plants and herbivores often investigate escalation or elaboration of plant defense and herbivore adaptations to overcome it. The main exceptions to the general pattern are studies that focus on small, sessile herbivores that share many features with plant pathogens, studies that incorporate both herbivores and pathogens into a single investigation, and studies that test aspects of Thompson's geographic mosaic theory for coevolution. We discuss the implications of these findings for future research. © 2017 New York Academy of Sciences.

Genome Content and Phylogenomics Reveal both Ancestral and Lateral Evolutionary Pathways in Plant-Pathogenic Streptomyces Species

PubMed Central

Huguet-Tapia, Jose C.; Lefebure, Tristan; Badger, Jonathan H.; Guan, Dongli; Stanhope, Michael J.

2016-01-01

Streptomyces spp. are highly differentiated actinomycetes with large, linear chromosomes that encode an arsenal of biologically active molecules and catabolic enzymes. Members of this genus are well equipped for life in nutrient-limited environments and are common soil saprophytes. Out of the hundreds of species in the genus Streptomyces, a small group has evolved the ability to infect plants. The recent availability of Streptomyces genome sequences, including four genomes of pathogenic species, provided an opportunity to characterize the gene content specific to these pathogens and to study phylogenetic relationships among them. Genome sequencing, comparative genomics, and phylogenetic analysis enabled us to discriminate pathogenic from saprophytic Streptomyces strains; moreover, we calculated that the pathogen-specific genome contains 4,662 orthologs. Phylogenetic reconstruction suggested that Streptomyces scabies and S. ipomoeae share an ancestor but that their biosynthetic clusters encoding the required virulence factor thaxtomin have diverged. In contrast, S. turgidiscabies and S. acidiscabies, two relatively unrelated pathogens, possess highly similar thaxtomin biosynthesis clusters, which suggests that the acquisition of these genes was through lateral gene transfer. PMID:26826232

Global climate change and vector-borne diseases

USGS Publications Warehouse

Ginsberg, H.S.

2002-01-01

Global warming will have different effects on different diseases because of the complex and idiosynchratic interactions between vectors, hosts, and pathogens that influence transmission dynamics of each pathogen. Human activities, including urbanization, rapid global travel, and vector management, have profound effects on disease transmission that can operate on more rapid time scales than does global climate change. The general concern about global warming encouraging the spread of tropical diseases is legitimate, but the effects vary among diseases, and the ecological implications are difficult to predict.

Genetic basis for rapidly evolved tolerance in the wild: adaptation to toxic pollutants by an estuarine fish species

EPA Science Inventory

Atlantic killifish (Fundulus heteroclitus) residing in some urban and industrialized estuaries of the US eastern seaboard demonstrate recently evolved and extreme tolerance to toxic aryl hydrocarbon pollutants, characterized as dioxin-like compounds (DLCs). Here we provide an unu...

Detection and Characterization of Cancer Cells and Pathogenic Bacteria Using Aptamer-Based Nano-Conjugates

PubMed Central

Gedi, Vinayakumar; Kim, Young-Pil

2014-01-01

Detection and characterization of cells using aptamers and aptamer-conjugated nanoprobes has evolved a great deal over the past few decades. This evolution has been driven by the easy selection of aptamers via in vitro cell-SELEX, permitting sensitive discrimination between target and normal cells, which includes pathogenic prokaryotic and cancerous eukaryotic cells. Additionally, when the aptamer-based strategies are used in conjunction with nanomaterials, there is the potential for cell targeting and therapeutic effects with improved specificity and sensitivity. Here we review recent advances in aptamer-based nano-conjugates and their applications for detecting cancer cells and pathogenic bacteria. The multidisciplinary research utilized in this field will play an increasingly significant role in clinical medicine and drug discovery. PMID:25268922

Bacterial spread from cell to cell: beyond actin-based motility.

PubMed

Kuehl, Carole J; Dragoi, Ana-Maria; Talman, Arthur; Agaisse, Hervé

2015-09-01

Several intracellular pathogens display the ability to propagate within host tissues by displaying actin-based motility in the cytosol of infected cells. As motile bacteria reach cell-cell contacts they form plasma membrane protrusions that project into adjacent cells and resolve into vacuoles from which the pathogen escapes, thereby achieving spread from cell to cell. Seminal studies have defined the bacterial and cellular factors that support actin-based motility. By contrast, the mechanisms supporting the formation of protrusions and their resolution into vacuoles have remained elusive. Here, we review recent advances in the field showing that Listeria monocytogenes and Shigella flexneri have evolved pathogen-specific mechanisms of bacterial spread from cell to cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent.

PubMed

States, S L; Huang, C I; Davis, S; Tufts, D M; Diuk-Wasser, M A

2017-06-01

Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R 0 , the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding - such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A distributed national network for label-free rapid identification of emerging pathogens

NASA Astrophysics Data System (ADS)

Robinson, J. Paul; Rajwa, Bartek P.; Dundar, M. Murat; Bae, Euiwon; Patsekin, Valery; Hirleman, E. Daniel; Roumani, Ali; Bhunia, Arun K.; Dietz, J. Eric; Davisson, V. Jo; Thomas, John G.

2011-05-01

Typical bioterrorism prevention scenarios assume well-known and well-characterized pathogens like anthrax or tularemia, which are serious public concerns if released into food and/or water supplies or distributed using other vectors. Common governmental contingencies include rapid response to these biological threats with predefined treatments and management operations. However, bioterrorist attacks may follow a far more sophisticated route. With the widely known and immense progress in genetics and the availability of molecular biology tools worldwide, the potential for malicious modification of pathogenic genomes is very high. Common non-pathogenic microorganisms could be transformed into dangerous, debilitating pathogens. Known pathogens could also be modified to avoid detection, because organisms are traditionally identified on the basis of their known physiological or genetic properties. In the absence of defined primers a laboratory using genetic biodetection methods such as PCR might be unable to quickly identify a modified microorganism. Our concept includes developing a nationwide database of signatures based on biophysical (such as elastic light scattering (ELS) properties and/or Raman spectra) rather than genetic properties of bacteria. When paired with a machine-learning system for emerging pathogen detection these data become an effective detection system. The approach emphasizes ease of implementation using a standardized collection of phenotypic information and extraction of biophysical features of pathogens. Owing to the label-free nature of the detection modalities ELS is significantly less costly than any genotypic or mass spectrometry approach.

Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

NASA Astrophysics Data System (ADS)

Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

2012-10-01

The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

PubMed

Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

2012-01-01

The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

Evolution of Mycobacterium tuberculosis.

PubMed

Behr, Marcel A

2013-01-01

Genomic studies have provided a refined understanding of the genetic diversity within the Mycobacterium genus, and more specifically within Mycobacterium tuberculosis. These results have informed a new perspective on the macro- and micro-evolution of the tubercle bacillus. In the first step, a M. kansasii-like opportunistic pathogen acquired new genes, through horizontal gene transfer, that enabled it to better exploit an intracellular niche and ultimately evolve into a professional pathogen. In the second step, different subspecies and strains of the M. tuberculosis complex emerged through mutation and deletion of unnecessary DNA. Understanding the differences between M. tuberculosis and related less pathogenic mycobacteria is expected to reveal key bacterial virulence mechanisms and provide opportunities to understand host resistance to mycobacterial infection. Understanding differences within the M. tuberculosis complex and the evolutionary forces shaping these differences is important for investigating the basis of its success as both a symbiont and a pathogen.

The role of the plasma membrane H+-ATPase in plant-microbe interactions.

PubMed

Elmore, James Mitch; Coaker, Gitta

2011-05-01

Plasma membrane (PM) H+-ATPases are the primary pumps responsible for the establishment of cellular membrane potential in plants. In addition to regulating basic aspects of plant cell function, these enzymes contribute to signaling events in response to diverse environmental stimuli. Here, we focus on the roles of the PM H+-ATPase during plant-pathogen interactions. PM H+-ATPases are dynamically regulated during plant immune responses and recent quantitative proteomics studies suggest complex spatial and temporal modulation of PM H+-ATPase activity during early pathogen recognition events. Additional data indicate that PM H+-ATPases cooperate with the plant immune signaling protein RIN4 to regulate stomatal apertures during bacterial invasion of leaf tissue. Furthermore, pathogens have evolved mechanisms to manipulate PM H+-ATPase activity during infection. Thus, these ubiquitous plant enzymes contribute to plant immune responses and are targeted by pathogens to increase plant susceptibility.

The proportional lack of archaeal pathogens: Do viruses/phages hold the key?

PubMed Central

Gill, Erin E; Brinkman, Fiona S L

2011-01-01

Although Archaea inhabit the human body and possess some characteristics of pathogens, there is a notable lack of pathogenic archaeal species identified to date. We hypothesize that the scarcity of disease-causing Archaea is due, in part, to mutually-exclusive phage and virus populations infecting Bacteria and Archaea, coupled with an association of bacterial virulence factors with phages or mobile elements. The ability of bacterial phages to infect Bacteria and then use them as a vehicle to infect eukaryotes may be difficult for archaeal viruses to evolve independently. Differences in extracellular structures between Bacteria and Archaea would make adsorption of bacterial phage particles onto Archaea (i.e. horizontal transfer of virulence) exceedingly hard. If phage and virus populations are indeed exclusive to their respective host Domains, this has important implications for both the evolution of pathogens and approaches to infectious disease control. PMID:21328413

The evolution of sex-specific virulence in infectious diseases

PubMed Central

Úbeda, Francisco; Jansen, Vincent A. A.

2016-01-01

Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females. PMID:27959327

Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

PubMed

Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

2007-07-27

Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

PubMed

Rao, Sheila; Schieber, Alexandria M Palaferri; O'Connor, Carolyn P; Leblanc, Mathias; Michel, Daniela; Ayres, Janelle S

2017-01-26

Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1β-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence. Copyright © 2017 Elsevier Inc. All rights reserved.

The evolution of sex-specific virulence in infectious diseases.

PubMed

Úbeda, Francisco; Jansen, Vincent A A

2016-12-13

Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females.

Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective

PubMed Central

Martínez-Chavarría, Luary C.; Vadyvaloo, Viveka

2015-01-01

Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens. PMID:26441890

Rapidly expanding range of highly pathogenic avian influenza viruses

USGS Publications Warehouse

Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

2015-01-01

The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

Rapidly Expanding Range of Highly Pathogenic Avian Influenza Viruses.

PubMed

Hall, Jeffrey S; Dusek, Robert J; Spackman, Erica

2015-07-01

The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus' propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens

Treesearch

Justin B. Runyon; Mark C. Mescher; Consuelo M. De Moraes

2010-01-01

Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling and response to herbivores and pathogens has expanded rapidly in recent years...

Blufensin1 Negatively Impacts Basal Defense in Response to Barley Powdery Mildew

USDA-ARS?s Scientific Manuscript database

Plants have evolved complex regulatory mechanisms to control the defense response against microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSIN1 (BLN1), a small peptide ...

Plant antimicrobial peptides

USDA-ARS?s Scientific Manuscript database

Disease afflicts crop productivity as well as nutritional attributes. Pathogens have the ability to mutate rapidly and thereby develop resistance to pesticides. Despite the plant’s multilayer of innate defense against pathogens, the latter are often able to penetrate and establish themselves on th...

Rapid Methods for the Detection of General Fecal Indicators

EPA Science Inventory

Specified that EPA should develop: appropriate and effective indicators for improving detection in a timely manner of pathogens in coastal waters appropriate, accurate, expeditious and cost-effective methods for the timely detection of pathogens in coastal waters

Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach.

PubMed

Perkins, Sarah E; Fenton, Andy

2006-07-01

Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.

Practical Value of Food Pathogen Traceability through Building a Whole-Genome Sequencing Network and Database

PubMed Central

Strain, Errol; Melka, David; Bunning, Kelly; Musser, Steven M.; Brown, Eric W.; Timme, Ruth

2016-01-01

The FDA has created a United States-based open-source whole-genome sequencing network of state, federal, international, and commercial partners. The GenomeTrakr network represents a first-of-its-kind distributed genomic food shield for characterizing and tracing foodborne outbreak pathogens back to their sources. The GenomeTrakr network is leading investigations of outbreaks of foodborne illnesses and compliance actions with more accurate and rapid recalls of contaminated foods as well as more effective monitoring of preventive controls for food manufacturing environments. An expanded network would serve to provide an international rapid surveillance system for pathogen traceback, which is critical to support an effective public health response to bacterial outbreaks. PMID:27008877

Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood

PubMed Central

Nölling, Jörk; Rapireddy, Srinivas; Amburg, Joel I.; Crawford, Elizabeth M.; Prakash, Ranjit A.; Rabson, Arthur R.

2016-01-01

ABSTRACT Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention. PMID:27094328

Pathogen Webs in Collapsing Honey Bee Colonies

PubMed Central

Cornman, R. Scott; Tarpy, David R.; Chen, Yanping; Jeffreys, Lacey; Lopez, Dawn; Pettis, Jeffery S.; vanEngelsdorp, Dennis; Evans, Jay D.

2012-01-01

Recent losses in honey bee colonies are unusual in their severity, geographical distribution, and, in some cases, failure to present recognized characteristics of known disease. Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens. Here we explore the incidence and abundance of currently known honey bee pathogens in colonies suffering from Colony Collapse Disorder (CCD), otherwise weak colonies, and strong colonies from across the United States. Although pathogen identities differed between the eastern and western United States, there was a greater incidence and abundance of pathogens in CCD colonies. Pathogen loads were highly covariant in CCD but not control hives, suggesting that CCD colonies rapidly become susceptible to a diverse set of pathogens, or that co-infections can act synergistically to produce the rapid depletion of workers that characterizes the disorder. We also tested workers from a CCD-free apiary to confirm that significant positive correlations among pathogen loads can develop at the level of individual bees and not merely as a secondary effect of CCD. This observation and other recent data highlight pathogen interactions as important components of bee disease. Finally, we used deep RNA sequencing to further characterize microbial diversity in CCD and non-CCD hives. We identified novel strains of the recently described Lake Sinai viruses (LSV) and found evidence of a shift in gut bacterial composition that may be a biomarker of CCD. The results are discussed with respect to host-parasite interactions and other environmental stressors of honey bees. PMID:22927991

Transcriptome Analysis of the Entomopathogenic Oomycete Lagenidium giganteum Reveals Putative Virulence Factors

PubMed Central

Quiroz Velasquez, Paula F.; Abiff, Sumayyah K.; Fins, Katrina C.; Conway, Quincy B.; Salazar, Norma C.; Delgado, Ana Paula; Dawes, Jhanelle K.; Douma, Lauren G.

2014-01-01

A combination of 454 pyrosequencing and Sanger sequencing was used to sample and characterize the transcriptome of the entomopathogenic oomycete Lagenidium giganteum. More than 50,000 high-throughput reads were annotated through homology searches. Several selected reads served as seeds for the amplification and sequencing of full-length transcripts. Phylogenetic analyses inferred from full-length cellulose synthase alignments revealed that L giganteum is nested within the peronosporalean galaxy and as such appears to have evolved from a phytopathogenic ancestor. In agreement with the phylogeny reconstructions, full-length L. giganteum oomycete effector orthologs, corresponding to the cellulose-binding elicitor lectin (CBEL), crinkler (CRN), and elicitin proteins, were characterized by domain organizations similar to those of pathogenicity factors of plant-pathogenic oomycetes. Importantly, the L. giganteum effectors provide a basis for detailing the roles of canonical CRN, CBEL, and elicitin proteins in the infectious process of an oomycete known principally as an animal pathogen. Finally, phylogenetic analyses and genome mining identified members of glycoside hydrolase family 5 subfamily 27 (GH5_27) as putative virulence factors active on the host insect cuticle, based in part on the fact that GH5_27 genes are shared by entomopathogenic oomycetes and fungi but are underrepresented in nonentomopathogenic genomes. The genomic resources gathered from the L. giganteum transcriptome analysis strongly suggest that filamentous entomopathogens (oomycetes and fungi) exhibit convergent evolution: they have evolved independently from plant-associated microbes, have retained genes indicative of plant associations, and may share similar cores of virulence factors, such as GH5_27 enzymes, that are absent from the genomes of their plant-pathogenic relatives. PMID:25107973

Rapid Analysis of Pharmacology for Infectious Diseases

PubMed Central

Hopkins, Andrew L; Bickerton, G. Richard; Carruthers, Ian M; Boyer, Stephen K; Rubin, Harvey; Overington, John P

2011-01-01

Pandemic, epidemic and endemic infectious diseases are united by a common problem: how do we rapidly and cost-effectively identify potential pharmacological interventions to treat infections? Given the large number of emerging and neglected infectious diseases and the fact that they disproportionately afflict the poorest members of the global society, new ways of thinking are required to develop high productivity discovery systems that can be applied to a large number of pathogens. The growing availability of parasite genome data provides the basis for developing methods to prioritize, a priori potential drug targets and analyze the pharmacological landscape of an infectious disease. Thus the overall objective of infectious disease informatics is to enable the rapid generation of plausible, novel medical hypotheses of test-able pharmacological experiments, by uncovering undiscovered relationships in the wealth of biomedical literature and databases that were collected for other purposes. In particular our goal is to identify potential drug targets present in a pathogen genome and prioritize which pharmacological experiments are most likely to discover drug-like lead compounds rapidly against a pathogen (i.e. which specific compounds and drug targets should be screened, in which assays and where they can be sourced). An integral part of the challenge is the development and integration of methods to predict druggability, essentiality, synthetic lethality and polypharmocology in pathogen genomes, while simultaneously integrating the inevitable issues of chemical tractability and the potential for acquired drug resistance from the start. PMID:21401504

Chromatin versus pathogens: the function of epigenetics in plant immunity.

PubMed

Ding, Bo; Wang, Guo-Liang

2015-01-01

To defend against pathogens, plants have developed a sophisticated innate immunity that includes effector recognition, signal transduction, and rapid defense responses. Recent evidence has demonstrated that plants utilize the epigenetic control of gene expression to fine-tune their defense when challenged by pathogens. In this review, we highlight the current understanding of the molecular mechanisms of histone modifications (i.e., methylation, acetylation, and ubiquitination) and chromatin remodeling that contribute to plant immunity against pathogens. Functions of key histone-modifying and chromatin remodeling enzymes are discussed.

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

PubMed Central

Byrne, Barry; Stack, Edwina; Gilmartin, Niamh; O'Kennedy, Richard

2009-01-01

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided. PMID:22408533

The genomes of Mycosphaerella graminicola and M. fijiensis

USDA-ARS?s Scientific Manuscript database

Mycosphaerella graminicola and M. fijiensis are two of the most important pathogens of wheat and banana, respectively. Both pathogens cause economically significant diseases that can be controlled with fungicides, but have rapidly developed resistance rendering chemical control less than satisfactor...

Personalized diagnostics and biosensors: a review of the biology and technology needed for personalized medicine.

PubMed

Ahmed, Minhaz Uddin; Saaem, Ishtiaq; Wu, Pae C; Brown, April S

2014-06-01

Exploiting the burgeoning fields of genomics, proteomics and metabolomics improves understanding of human physiology and, critically, the mutations that signal disease susceptibility. Through these emerging fields, rational design approaches to diagnosis, drug development and ultimately personalized medicine are possible. Personalized medicine and point-of-care testing techniques must fulfill a host of constraints for real-world applicability. Point-of-care devices (POCDs) must ultimately provide a cost-effective alternative to expensive and time-consuming laboratory tests in order to assist health care personnel with disease diagnosis and treatment decisions. Sensor technologies are also expanding beyond the more traditional classes of biomarkers--nucleic acids and proteins--to metabolites and direct detection of pathogens, ultimately increasing the palette of available techniques for the use of personalized medicine. The technologies needed to perform such diagnostics have also been rapidly evolving, with each generation being increasingly sensitive and selective while being more resource conscious. Ultimately, the final hurdle for all such technologies is to be able to drive consumer adoption and achieve a meaningful medical outcome for the patient.

DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

PubMed Central

Lee, Andrew H.; Symington, Lorraine S.

2014-01-01

SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

West nile virus: characteristics of an african virus adapting to the third millennium world.

PubMed

Monini, Marina; Falcone, Emiliana; Busani, Luca; Romi, Roberto; Ruggeri, Franco Maria

2010-04-22

The emergence and spread of West Nile Virus (WNV) from North through South America during the last decade, and the recent outbreaks of disease in both humans and horses in Europe suggest that the epidemiology of this infection is evolving. WNV is now considered among the emerging threats for both human and veterinary public health in areas like Europe where it was previously regarded to as an exotic agent. Further knowledge has built up from studies investigating the characteristics of the virus and its genome evolution capacity, the adaptation to new avian host species, the changes in vector competence and biology, and the host-pathogen interactions, including the immune response. Also, the new needs for preparedness to future major outbursts of disease have stimulated research on virus detection and characterization, filling the gaps in both specialized diagnostic technology and the need for field rapid assays. This review will present an overview of WNV virology, remarking the impact of virus diversity and evolution on theoretical and practical aspects involved in both risk definition, detection and control of infection.

Current Technology in the Discovery and Development of Novel Antibacterials.

PubMed

Chung, Pooi Yin

2018-01-01

Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis. This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria. With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Autophagy and bacterial infection: an evolving arms race.

PubMed

Choy, Augustine; Roy, Craig R

2013-09-01

Autophagy is an important membrane transport pathway that is conserved among eukaryotic cells. Although first described as an intracellular catabolic pathway used to break down self-components, autophagy has been found to play an important role in the elimination of intracellular pathogens. A variety of host mechanisms exist for recognizing and targeting intracellular bacteria to autophagosomes. Several intracellular bacteria have evolved ways to manipulate, inhibit, or avoid autophagy in order to survive in the cell. Thus, the autophagy pathway can be viewed as an evolutionarily conserved host response to infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Novel R tools for analysis of genome-wide population genetic data with emphasis on clonality

USDA-ARS?s Scientific Manuscript database

To gain a detailed understanding of how plant microbes evolve and adapt to hosts, pesticides, and other factors, knowledge of the population dynamics and evolutionary history of populations is crucial. Plant pathogen populations are often clonal or partially clonal which requires different analytica...

The role of somatic recombination in natural populations of the root pathogen Armillaria mellea

USDA-ARS?s Scientific Manuscript database

Fungi have evolved various mechanisms of shuffling genetic material, which can occur in the absence of fruiting and meiosis. In the homobasidiomycete Armillaria (causal agent of Armillaria root disease), the predominant vegetative stage is diploid. Diploid and haploid mycelia can fuse and undergo ka...

The effect of zinc limitation on the transcriptome of Pseudomonas fluorescens Pf-5

USDA-ARS?s Scientific Manuscript database

Pseudomonas fluorescens Pf-5 is a soil bacterium that can protect several plant species from diseases caused by fungal and bacterial pathogens. Zinc is a vital micronutrient for bacteria but is deficient in some soil environments and toxic in large quantities. Hence, bacteria have evolved elaborate ...

Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog

USDA-ARS?s Scientific Manuscript database

Leptospira interrogans is the causative agent of leptospirosis, a zoonosis of global significance. Iron is essential for growth of most bacterial species. Since availability of iron is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In ...

Practical aspects of vaccination of poultry against avian influenza virus

USDA-ARS?s Scientific Manuscript database

Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic (HP) AIV has become endemic in several regions of the world. Vaccination f...

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMARON2 pair

USDA-ARS?s Scientific Manuscript database

Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the...

Virtual Genomes in Flux: An Interplay of Neutrality and Adaptability Explains Genome Expansion and Streamlining

PubMed Central

Cuypers, Thomas D.; Hogeweg, Paulien

2012-01-01

The picture that emerges from phylogenetic gene content reconstructions is that genomes evolve in a dynamic pattern of rapid expansion and gradual streamlining. Ancestral organisms have been estimated to possess remarkably rich gene complements, although gene loss is a driving force in subsequent lineage adaptation and diversification. Here, we study genome dynamics in a model of virtual cells evolving to maintain homeostasis. We observe a pattern of an initial rapid expansion of the genome and a prolonged phase of mutational load reduction. Generally, load reduction is achieved by the deletion of redundant genes, generating a streamlining pattern. Load reduction can also occur as a result of the generation of highly neutral genomic regions. These regions can expand and contract in a neutral fashion. Our study suggests that genome expansion and streamlining are generic patterns of evolving systems. We propose that the complex genotype to phenotype mapping in virtual cells as well as in their biological counterparts drives genome size dynamics, due to an emerging interplay between adaptation, neutrality, and evolvability. PMID:22234601

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

PubMed

Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

2018-01-01

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

Rapid Magnetic Nanobiosensor for the detection of Serratia marcescen

NASA Astrophysics Data System (ADS)

Aljabali, Alaa A. A.; Hussein, Emad; Aljumaili, Omar; Zoubi, Mazhar Al; Altrad, Bahaa; Albatayneh, Khaled; Al-razaq, Mutaz A. Abd

2018-02-01

The development of rapid, sensitive, accurate and reliable bacterial detection methods are of keen interest to ensure food safety and hospital security. Therefore, the development of a fast, specific, low-cost and trusted methods is in high demand. Magnetic nanoparticles with their unique material properties have been utilized as a tool for pathogen detection. Here, we present a novel iron oxide nanoparticles labeled with specific targeting antibodies to improve specificity and extend the use of nanoparticles as nanosensors. The results indicated that antibody labeled iron oxide platform that binds specifically to Serriata marcescenst in a straightforward method is very specific and sensitive. The system is capable of rapid and specific detection of various clinically relevant bacterial species, with sensitivity down to single bacteria. The generic platform could be used to identify pathogens for a variety of applications rapidly.

Rapid pathogen detection with bacterial-assembled magnetic mesoporous silica.

PubMed

Lee, Soo Youn; Lee, Jiho; Lee, Hye Sun; Chang, Jeong Ho

2014-03-15

We report rapid and accurate pathogen detection by coupling with high efficiency magnetic separation of pathogen by Ni(2+)-heterogeneous magnetic mesoporous silica (Ni-HMMS) and real time-polymerase chain reaction (RT-PCR) technique. Ni-HMMS was developed with a significant incorporation of Fe particles within the silica mesopores by programmed thermal hydrogen reaction and functionalized with Ni(2+) ion on the surface by the wet impregnation process. High abundant Ni(2+) ions on the Ni-HMMS surface were able to assemble with cell wall component protein NikA (nickel-binding membrane protein), which contains several pathogenic bacteria including Escherichia coli O157:H7. NikA protein expression experiment showed the outstanding separation rate of the nikA gene-overexpressed E. coli (pSY-Nik) when comparing with wild-type E. coli (44.5 ± 13%) or not over-expressed E. coli (pSY-Nik) (53.2 ± 2.7%). Moreover, Ni-HMMS showed lower obstacle effect by large reaction volume (10 mL) than spherical core/shell-type silica magnetic nanoparticles functionalized with Ni(2+) (ca. 40 nm-diameters). Finally, the Ni-HMMS was successfully assessed to separate pathogenic E. coli O157:H7 and applied to direct and rapid RT-PCR to quantitative detection at ultralow concentration (1 Log10 cfu mL(-1)) in the real samples (milk and Staphylococcus aureus culture broth) without bacterial amplification and DNA extraction step. © 2013 Elsevier B.V. All rights reserved.

Continuous-Flow Detector for Rapid Pathogen Identification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barrett, Louise M.; Skulan, Andrew J.; Singh, Anup K.

2006-09-01

This report describes the continued development of a low-power, portable detector for the rapid identification of pathogens such as B. anthracis and smallpox. Based on our successful demonstration of the continuous filter/concentrator inlet, we believe strongly that the inlet section will enable differentiation between viable and non-viable populations, between types of cells, and between pathogens and background contamination. Selective, continuous focusing of particles in a microstream enables highly selective and sensitive identification using fluorescently labeled antibodies and other receptors such as peptides, aptamers, or small ligands to minimize false positives. Processes such as mixing and lysing will also benefit frommore » the highly localized particle streams. The concentrator is based on faceted prisms to contract microfluidic flows while maintaining uniform flowfields. The resulting interfaces, capable of high throughput, serve as high-, low-, and band-pass filters to direct selected bioparticles to a rapid, affinity-based detection system. The proposed device is superior to existing array-based detectors as antibody-pathogen binding can be accomplished in seconds rather than tens of minutes or even hours. The system is being designed to interface with aerosol collectors under development by the National Laboratories or commercial systems. The focused stream is designed to be interrogated using diode lasers to differentiate pathogens by light scattering. Identification of particles is done using fluorescently labeled antibodies to tag the particles, followed by multiplexed laser-induced fluorescence (LIF) detection (achieved by labeling each antibody with a different dye).« less

Microbial antagonism as a potential solution for controlling selected root pathogens of crops

NASA Astrophysics Data System (ADS)

Cooper, Sarah; Agnew, Linda; Pereg, Lily

2016-04-01

Root pathogens of crops can cause large reduction in yield, however, there is a limited range of effective methods to control such pathogens. Soilborne pathogens that infect roots often need to survive in the rhizosphere, where there is high competition from other organisms. In such hot spots of microbial activity and growth, supported by root exudates, microbes have evolved antagonistic mechanisms that give them competitive advantages in winning the limited resources. Among these mechanisms is antibiosis, with production of some significant antifungal compounds including, antibiotics, volatile organic compounds, hydrogen cyanide and lytic enzymes. Some of these mechanisms may suppress disease through controlling the growth of root pathogens. In this project we isolated various fungi and bacteria that suppress the growth of cotton pathogens in vitro. The pathogen-suppressive microbes were isolated from cotton production soils that are under different management strategies, with and without the use of organic amendments. The potential of pathogen-suppressing microbes for controlling the black root rot disease, caused by the soilborne pathogen Thielaviopsis basicola, was confirmed using soil assays. We identified isolates with potential use as inoculant for cotton production in Australia. Having isolated a diverse group of antagonistic microbes enhances the probability that some would survive well in the soil and provide an alternative approach to address the problem of root disease affecting agricultural crops.

Targeting of the hydrophobic metabolome by pathogens.

PubMed

Helms, J Bernd; Kaloyanova, Dora V; Strating, Jeroen R P; van Hellemond, Jaap J; van der Schaar, Hilde M; Tielens, Aloysius G M; van Kuppeveld, Frank J M; Brouwers, Jos F

2015-05-01

The hydrophobic molecules of the metabolome - also named the lipidome - constitute a major part of the entire metabolome. Novel technologies show the existence of a staggering number of individual lipid species, the biological functions of which are, with the exception of only a few lipid species, unknown. Much can be learned from pathogens that have evolved to take advantage of the complexity of the lipidome to escape the immune system of the host organism and to allow their survival and replication. Different types of pathogens target different lipids as shown in interaction maps, allowing visualization of differences between different types of pathogens. Bacterial and viral pathogens target predominantly structural and signaling lipids to alter the cellular phenotype of the host cell. Fungal and parasitic pathogens have complex lipidomes themselves and target predominantly the release of polyunsaturated fatty acids from the host cell lipidome, resulting in the generation of eicosanoids by either the host cell or the pathogen. Thus, whereas viruses and bacteria induce predominantly alterations in lipid metabolites at the host cell level, eukaryotic pathogens focus on interference with lipid metabolites affecting systemic inflammatory reactions that are part of the immune system. A better understanding of the interplay between host-pathogen interactions will not only help elucidate the fundamental role of lipid species in cellular physiology, but will also aid in the generation of novel therapeutic drugs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evolution of acuteness in pathogen metapopulations: conflicts between “classical” and invasion-persistence trade-offs

PubMed Central

Shrestha, Sourya; Bjørnstad, Ottar N.; King, Aaron A.

2014-01-01

Classical life-history theory predicts that acute, immunizing pathogens should maximize between-host transmission. When such pathogens induce violent epidemic outbreaks, however, a pathogen’s short-term advantage at invasion may come at the expense of its ability to persist in the population over the long term. Here, we seek to understand how the classical and invasion-persistence trade-offs interact to shape pathogen life-history evolution as a function of the size and structure of the host population. We develop an individual-based infection model at three distinct levels of organization: within an individual host, among hosts within a local population, and among local populations within a metapopulation. We find a continuum of evolutionarily stable pathogen strategies. At one end of the spectrum—in large well-mixed populations—pathogens evolve to greater acuteness to maximize between-host transmission: the classical trade-off theory applies in this regime. At the other end of the spectrum—when the host population is broken into many small patches—selection favors less acute pathogens, which persist longer within a patch and thereby achieve enhanced between-patch transmission: the invasion-persistence tradeoff dominates in this regime. Between these extremes, we explore the effects of the size and structure of the host population in determining pathogen strategy. In general, pathogen strategies respond to evolutionary pressures arising at both scales. PMID:25214895

CONDUCTING-POLYMER NANOWIRE IMMUNOSENSOR ARRAYS FOR MICROBIAL PATHOGENS

EPA Science Inventory

The lack of methods for routine rapid and sensitive detection and quantification of specific pathogens has limited the amount of information available on their occurrence in drinking water and other environmental samples. The nanowire biosensor arrays developed in this study w...

Curriculum evaluation and revision in a nascent field: the utility of the retrospective pretest--posttest model in a homeland security program of study.

PubMed

Pelfrey, William V; Pelfrey, William V

2009-02-01

Although most academic disciplines evolve at a measured pace, the emerging field of homeland security must, for reasons of safety and security, evolve rapidly. The Department of Homeland Security sponsored the establishment of a graduate educational program for key officials holding homeland security roles. Because homeland security is a nascent field, the establishment of a program curriculum was forced to draw from a variety of disciplines. Curriculum evaluation was complicated by the rapid changes occurring in the emerging discipline, producing response shift bias, and interfering with the pre-post assessments. To compensate for the validity threat associated with response shift bias, a retrospective pretest-posttest evaluative methodology was used. Data indicate the program has evolved in a significant and orderly fashion and these data support the use of this innovative evaluation approach in the development of any discipline.

A Rapid and Simple Real-Time PCR Assay for Detecting Foodborne Pathogenic Bacteria in Human Feces.

PubMed

Hanabara, Yutaro; Ueda, Yutaka

2016-11-22

A rapid, simple method for detecting foodborne pathogenic bacteria in human feces is greatly needed. Here, we examined the efficacy of a method that employs a combination of a commercial PCR master mix, which is insensitive to PCR inhibitors, and a DNA extraction method which used sodium dodecyl benzene sulfonate (SDBS), and Tween 20 to counteract the inhibitory effects of SDBS on the PCR assay. This method could detect the target genes (stx1 and stx2 of enterohemorrhagic Escherichia coli, invA of Salmonella Enteritidis, tdh of Vibrio parahaemolyticus, gyrA of Campylobacter jejuni, ceuE of Campylobacter coli, SEA of Staphylococcus aureus, ces of Bacillus cereus, and cpe of Clostridium perfringens) in a fecal suspension containing 1.0 × 10 1 to 1.0 × 10 3 CFU/ml. Furthermore, the assay was neither inhibited nor influenced by individual differences among the fecal samples of 10 subjects or fecal concentration (40-160 mg/ml in the fecal suspension). When we attempted to detect the genes of pathogenic bacteria in 4 actual clinical cases, we found that this method was more sensitive than standard culture method. These results showed that this assay is a rapid, simple detection method for foodborne pathogenic bacteria in human feces.

Sensitive Detection of Xanthomonas oryzae Pathovars oryzae and oryzicola by Loop-Mediated Isothermal Amplification

PubMed Central

Lang, Jillian M.; Langlois, Paul; Nguyen, Marian Hanna R.; Triplett, Lindsay R.; Purdie, Laura; Holton, Timothy A.; Djikeng, Appolinaire; Vera Cruz, Casiana M.; Verdier, Valérie

2014-01-01

Molecular diagnostics for crop diseases can enhance food security by enabling the rapid identification of threatening pathogens and providing critical information for the deployment of disease management strategies. Loop-mediated isothermal amplification (LAMP) is a PCR-based tool that allows the rapid, highly specific amplification of target DNA sequences at a single temperature and is thus ideal for field-level diagnosis of plant diseases. We developed primers highly specific for two globally important rice pathogens, Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight (BB) disease, and X. oryzae pv. oryzicola, the causal agent of bacterial leaf streak disease (BLS), for use in reliable, sensitive LAMP assays. In addition to pathovar distinction, two assays that differentiate X. oryzae pv. oryzae by African or Asian lineage were developed. Using these LAMP primer sets, the presence of each pathogen was detected from DNA and bacterial cells, as well as leaf and seed samples. Thresholds of detection for all assays were consistently 104 to 105 CFU ml−1, while genomic DNA thresholds were between 1 pg and 10 fg. Use of the unique sequences combined with the LAMP assay provides a sensitive, accurate, rapid, simple, and inexpensive protocol to detect both BB and BLS pathogens. PMID:24837384

Frequency of word-use predicts rates of lexical evolution throughout Indo-European history.

PubMed

Pagel, Mark; Atkinson, Quentin D; Meade, Andrew

2007-10-11

Greek speakers say "omicronupsilonrho", Germans "schwanz" and the French "queue" to describe what English speakers call a 'tail', but all of these languages use a related form of 'two' to describe the number after one. Among more than 100 Indo-European languages and dialects, the words for some meanings (such as 'tail') evolve rapidly, being expressed across languages by dozens of unrelated words, while others evolve much more slowly--such as the number 'two', for which all Indo-European language speakers use the same related word-form. No general linguistic mechanism has been advanced to explain this striking variation in rates of lexical replacement among meanings. Here we use four large and divergent language corpora (English, Spanish, Russian and Greek) and a comparative database of 200 fundamental vocabulary meanings in 87 Indo-European languages to show that the frequency with which these words are used in modern language predicts their rate of replacement over thousands of years of Indo-European language evolution. Across all 200 meanings, frequently used words evolve at slower rates and infrequently used words evolve more rapidly. This relationship holds separately and identically across parts of speech for each of the four language corpora, and accounts for approximately 50% of the variation in historical rates of lexical replacement. We propose that the frequency with which specific words are used in everyday language exerts a general and law-like influence on their rates of evolution. Our findings are consistent with social models of word change that emphasize the role of selection, and suggest that owing to the ways that humans use language, some words will evolve slowly and others rapidly across all languages.

Prospective evaluation of a high multiplexing real-time polymerase chain reaction array for the rapid identification and characterization of bacteria causative of nosocomial pneumonia from clinical specimens: a proof-of-concept study.

PubMed

Roisin, S; Huang, T-D; de Mendonça, R; Nonhoff, C; Bogaerts, P; Hites, M; Delaere, B; Hamels, S; de Longueville, F; Glupczynski, Y; Denis, O

2018-01-01

The purpose of this study was evaluation of the VAPChip assay based on the "Rapid-Array-PCR-technology" which targets 13 respiratory pathogens and 24 β-lactam resistance genes directly on respiratory clinical specimens. The first step included analysis of 45 respiratory specimens in order to calibrate and determine the threshold for target genes. The second prospective step involved 85 respiratory samples from patients suspected of nosocomial pneumonia collected in two academic hospitals over an 8-month period. Results of the VAPChip assay were compared to routine methods. The first step showed a large proportion of positive signals for H. influenzae and/or S. pneumoniae. For identification, discrepancies were observed in seven samples. Thresholds were adapted and two probes were re-designed to create a new version of the cartridge. In the second phase, sensitivity and specificity of the VAPchip for bacterial identification were 72.9% and 99.1%, respectively. Seventy (82%) pathogens were correctly identified by both methods. Nine pathogens detected by the VAPChip were culture negative and 26 pathogens identified by culture were VAPChip negative. For resistance mechanisms, 11 probes were positive without identification of pathogens with an antimicrobial-susceptibility testing compatible by culture. However, the patient's recent microbiological history was able to explain most of these positive signals. The VAPChip assay simultaneously detects different pathogens and resistance mechanisms directly from clinical samples. This system seems very promising but the extraction process needs to be automated for routine implementation. This kind of rapid point-of-care automated platform permitting a syndromic approach will be the future challenge in the management of infectious diseases.

Colonize, evade, flourish

PubMed Central

Rubin, Erica J; Trent, M Stephen

2013-01-01

Helicobacter pylori is an adapted gastric pathogen that colonizes the human stomach, causing severe gastritis and gastric cancer. A hallmark of infection is the ability of this organism to evade detection by the human immune system. H. pylori has evolved a number of features to achieve this, many of which involve glyco-conjugates including the lipopolysaccharide, peptidoglycan layer, glycoproteins, and glucosylated cholesterol. These major bacterial components possess unique features from those of other gram-negative organisms, including differences in structure, assembly, and modification. These defining characteristics of H. pylori glycobiology help the pathogen establish a long-lived infection by providing camouflage, modulating the host immune response, and promoting virulence mechanisms. In this way, glyco-conjugates are essential for H. pylori pathogenicity and survival, allowing it to carve out a niche in the formidable environment of the human stomach. PMID:23859890

Increased detection of mastitis pathogens by real-time PCR compared to bacterial culture.

PubMed

Keane, O M; Budd, K E; Flynn, J; McCoy, F

2013-09-21

Rapid and accurate identification of mastitis pathogens is important for disease control. Bacterial culture and isolate identification is considered the gold standard in mastitis diagnosis but is time consuming and results in many culture-negative samples. Identification of mastitis pathogens by PCR has been proposed as a fast and sensitive alternative to bacterial culture. The results of bacterial culture and PCR for the identification of the aetiological agent of clinical mastitis were compared. The pathogen identified by traditional culture methods was also detected by PCR in 98 per cent of cases indicating good agreement between the positive results of bacterial culture and PCR. A mastitis pathogen could not be recovered from approximately 30 per cent of samples by bacterial culture, however, an aetiological agent was identified by PCR in 79 per cent of these samples. Therefore, a mastitis pathogen was detected in significantly more milk samples by PCR than by bacterial culture (92 per cent and 70 per cent, respectively) although the clinical relevance of PCR-positive culture-negative results remains controversial. A mixed infection of two or more mastitis pathogens was also detected more commonly by PCR. Culture-negative samples due to undetected Staphylococcus aureus infections were rare. The use of PCR technology may assist in rapid mastitis diagnosis, however, accurate interpretation of PCR results in the absence of bacterial culture remains problematic.

The design of a microfluidic biochip for the rapid, multiplexed detection of foodborne pathogens by surface plasmon resonance imaging

NASA Astrophysics Data System (ADS)

Zordan, Michael D.; Grafton, Meggie M. G.; Park, Kinam; Leary, James F.

2010-02-01

The rapid detection of foodborne pathogens is increasingly important due to the rising occurrence of contaminated food supplies. We have previously demonstrated the design of a hybrid optical device that has the capability to perform realtime surface plasmon resonance (SPR) and epi-fluorescence imaging. We now present the design of a microfluidic biochip consisting of a two-dimensional array of functionalized gold spots. The spots on the array have been functionalized with capture peptides that specifically bind E. coli O157:H7 or Salmonella enterica. This array is enclosed by a PDMS microfluidic flow cell. A magnetically pre-concentrated sample is injected into the biochip, and whole pathogens will bind to the capture array. The previously constructed optical device is being used to detect the presence and identity of captured pathogens using SPR imaging. This detection occurs in a label-free manner, and does not require the culture of bacterial samples. Molecular imaging can also be performed using the epi-fluorescence capabilities of the device to determine pathogen state, or to validate the identity of the captured pathogens using fluorescently labeled antibodies. We demonstrate the real-time screening of a sample for the presence of E. coli O157:H7 and Salmonella enterica. Additionally the mechanical properties of the microfluidic flow cell will be assessed. The effect of these properties on pathogen capture will be examined.

Fungal Production and Manipulation of Plant Hormones.

PubMed

Fonseca, Sandra; Radhakrishnan, Dhanya; Prasad, Kalika; Chini, Andrea

2018-01-01

Living organisms are part of a highly interconnected web of interactions, characterised by species nurturing, competing, parasitizing and preying on one another. Plants have evolved cooperative as well as defensive strategies to interact with neighbour organisms. Among these, the plant-fungus associations are very diverse, ranging from pathogenic to mutualistic. Our current knowledge of plant-fungus interactions suggests a sophisticated coevolution to ensure dynamic plant responses to evolving fungal mutualistic/pathogenic strategies. The plant-fungus communication relies on a rich chemical language. To manipulate the plant defence mechanisms, fungi produce and secrete several classes of biomolecules, whose modeof- action is largely unknown. Upon perception of the fungi, plants produce phytohormones and a battery of secondary metabolites that serve as defence mechanism against invaders or to promote mutualistic associations. These mutualistic chemical signals can be co-opted by pathogenic fungi for their own benefit. Among the plant molecules regulating plant-fungus interaction, phytohormones play a critical role since they modulate various aspects of plant development, defences and stress responses. Intriguingly, fungi can also produce phytohormones, although the actual role of fungalproduced phytohormones in plant-fungus interactions is poorly understood. Here, we discuss the recent advances in fungal production of phytohormone, their putative role as endogenous fungal signals and how fungi manipulate plant hormone balance to their benefits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of saline tolerance among genetically similar species of Fusarium and Meloidogyne recovered from marine and terrestrial habitats

NASA Astrophysics Data System (ADS)

Elmer, W. H.; LaMondia, J. A.

2014-08-01

Successful plant pathogens co-evolve and adapt to the environmental constraints placed on host plants. We compared the salt tolerance of two salt marsh pathogens, Fusarium palustre and Meloidogyne spartinae, to genetically related terrestrial species, F. sporotrichioides and Meloidogyne hapla, to assess whether the salt marsh species had acquired selective traits for persisting in saline environments or if salt tolerance was comparable among Fusarium and Meloidogyne species. Comparisons of both species were made in vitro in vessels containing increasing concentration of NaCl. We observed that F. palustre was more tolerant to NaCl than F. sporotrichioides. The radial expansion of F. palustre on NaCl-amended agar plates was unaffected by increasing concentrations up to 0.3 M. F. sporotrichioides showed large reductions in growth at the same concentrations. Survival of M. hapla was greatest at 0 M, and reduced by half in a 0.3 M solution for 4 days. No juveniles survived exposure to 0.3 M NaCl for 12 days. M. spartinae survived at all NaCl concentrations tested, including 1.0 M for at least 12 days. These findings are consistent with the hypothesis that marine organisms in the upper tidal zone must osmoregulate to withstand a wide range of salinity and provide evidence that these pathogens evolved in saline conditions and are not recent introductions from terrestrial niches.

The role of immunostimulatory nucleic acids in septic shock

PubMed Central

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V; Tai, TC; Saleh, Mazen; Parrillo, Joseph E; Kumar, Anand; Kumar, Aseem

2012-01-01

Sepsis and its associated syndromes represent the systemic host response to severe infection and is manifested by varying degrees of hypotension, coagulopathy, and multiorgan dysfunction. Despite great efforts being made to understand this condition and designing therapies to treat sepsis, mortality rates are still high in septic patients. Characterization of the complex molecular signaling networks between the various components of host-pathogen interactions, highlights the difficulty in identifying a single driving force responsible for sepsis. Although triggering the inflammatory response is generally considered as protective against pathogenic threats, the interplay between the signaling pathways that are induced or suppressed during sepsis may harm the host. Numerous surveillance mechanisms have evolved to discriminate self from foreign agents and accordingly provoke an effective cellular response to target the pathogens. Nucleic acids are not only an essential genetic component, but sensing their molecular signature is also an important quality control mechanism which has evolved to maintain the integrity of the human genome. Evidence that has accumulated recently indicated that distinct pattern recognition receptors sense nucleic acids released from infectious organisms or from damaged host cells, resulting in the modulation of intracellular signalling cascades. Immunoreceptor-mediated detection of these nucleic acids induces antigen-specific immunity, secretion of proinflammatory cytokines and reactive oxygen/nitrogen species and thus are implicated in a range of diseases including septic shock. PMID:22328944

Practical Value of Food Pathogen Traceability through Building a Whole-Genome Sequencing Network and Database.

PubMed

Allard, Marc W; Strain, Errol; Melka, David; Bunning, Kelly; Musser, Steven M; Brown, Eric W; Timme, Ruth

2016-08-01

The FDA has created a United States-based open-source whole-genome sequencing network of state, federal, international, and commercial partners. The GenomeTrakr network represents a first-of-its-kind distributed genomic food shield for characterizing and tracing foodborne outbreak pathogens back to their sources. The GenomeTrakr network is leading investigations of outbreaks of foodborne illnesses and compliance actions with more accurate and rapid recalls of contaminated foods as well as more effective monitoring of preventive controls for food manufacturing environments. An expanded network would serve to provide an international rapid surveillance system for pathogen traceback, which is critical to support an effective public health response to bacterial outbreaks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Detection of Salmonella enteritidis Using a Miniature Optical Surface Plasmon Resonance Biosensor

NASA Astrophysics Data System (ADS)

Son, J. R.; Kim, G.; Kothapalli, A.; Morgan, M. T.; Ess, D.

2007-04-01

The frequent outbreaks of foodborne illness demand rapid detection of foodborne pathogens. Unfortunately, conventional methods for pathogen detection and identification are labor-intensive and take days to complete. Biosensors have shown great potential for the rapid detection of foodborne pathogens. Surface plasmon resonance (SPR) sensors have been widely adapted as an analysis tool for the study of various biological binding reactions. SPR biosensors could detect antibody-antigen bindings on the sensor surface by measuring either a resonance angle or refractive index value. In this study, the feasibility of a miniature SPR sensor (Spreeta, TI, USA) for detection of Salmonella enteritidis has been evaluated. Anti-Salmonella antibodies were immobilized on the gold sensor surface by using neutravidin. Salmonella could be detected by the Spreeta biosensor at concentrations down to 105 cfu/ml.

AUTOMATED BIOCHEMICAL IDENTIFICATION OF BACTERIAL FISH PATHOGENS USING THE ABBOTT QUANTUM II

EPA Science Inventory

The Quantum II, originally designed by Abbott Diagnostics for automated rapid identification of members of Enterobacteriaceae, was adapted for the identification of bacterial fish pathogens. he instrument operates as a spectrophotometer at a wavelength of 492.600 nm. ample cartri...

Light Scattering based detection of food pathogens

USDA-ARS?s Scientific Manuscript database

The current methods for detecting foodborne pathogens are mostly destructive (i.e., samples need to be pretreated), and require time, personnel, and laboratories for analyses. Optical methods including light scattering based techniques have gained a lot of attention recently due to its their rapid a...

P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster

USDA-ARS?s Scientific Manuscript database

Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect transmitted infectious diseases. The fact that many viruses carry...

Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. [Corrected].

PubMed

Wu, Liang; Chen, Huan; Curtis, Chad; Fu, Zheng Qing

2014-01-01

Plant resistance (R) proteins perceive specific pathogen effectors from diverse plant pathogens to initiate defense responses, designated effector-triggered immunity (ETI). Plant R proteins are mostly nucleotide binding-leucine rich repeat (NB-LRR) proteins, which recognize pathogen effectors directly or indirectly through sophisticated mechanisms. Upon activation by effector proteins, R proteins elicit robust defense responses, including a rapid burst of reactive oxygen species (ROS), induced biosynthesis and accumulation of salicylic acid (SA), a rapid programmed cell death (PCD) called hypersensitive response (HR) at the infection sites, and increased expression of pathogenesis-related (PR) genes. Initiation of ETI is correlated with a complex network of defense signaling pathways, resulting in defensive cellular responses and large-scale transcriptional reprogramming events. In this review, we highlight important recent advances on the recognition of effectors, regulation and activation of plant R proteins, dynamic intracellular trafficking of R proteins, induction of cell death, and transcriptional reprogramming associated with ETI. Current knowledge gaps and future research directions are also discussed in this review.

Molecular Biosensors for Electrochemical Detection of Infectious Pathogens in Liquid Biopsies: Current Trends and Challenges

PubMed Central

Yáñez-Sedeño, Paloma

2017-01-01

Rapid and reliable diagnosis of infectious diseases caused by pathogens, and timely initiation of appropriate treatment are critical determinants to promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in electrochemical affinity biosensors have demonstrated to surpass conventional standards in regards to time, simplicity, accuracy and cost in this field. The tremendous potential offered by electrochemical affinity biosensors to detect on-site infectious pathogens at clinically relevant levels in scarcely treated body fluids is clearly stated in this review. The development and application of selected examples using different specific receptors, assay formats and electrochemical approaches focusing on the determination of specific circulating biomarkers of different molecular (genetic, regulatory and functional) levels associated with bacterial and viral pathogens are critically discussed. Existing challenges still to be addressed and future directions in this rapidly advancing and highly interesting field are also briefly pointed out. PMID:29099764

Whole-Genome Sequencing in Outbreak Analysis

PubMed Central

Turner, Stephen D.; Riley, Margaret F.; Petri, William A.; Hewlett, Erik L.

2015-01-01

SUMMARY In addition to the ever-present concern of medical professionals about epidemics of infectious diseases, the relative ease of access and low cost of obtaining, producing, and disseminating pathogenic organisms or biological toxins mean that bioterrorism activity should also be considered when facing a disease outbreak. Utilization of whole-genome sequencing (WGS) in outbreak analysis facilitates the rapid and accurate identification of virulence factors of the pathogen and can be used to identify the path of disease transmission within a population and provide information on the probable source. Molecular tools such as WGS are being refined and advanced at a rapid pace to provide robust and higher-resolution methods for identifying, comparing, and classifying pathogenic organisms. If these methods of pathogen characterization are properly applied, they will enable an improved public health response whether a disease outbreak was initiated by natural events or by accidental or deliberate human activity. The current application of next-generation sequencing (NGS) technology to microbial WGS and microbial forensics is reviewed. PMID:25876885

Molecular Biosensors for Electrochemical Detection of Infectious Pathogens in Liquid Biopsies: Current Trends and Challenges.

PubMed

Campuzano, Susana; Yáñez-Sedeño, Paloma; Pingarrón, José Manuel

2017-11-03

Rapid and reliable diagnosis of infectious diseases caused by pathogens, and timely initiation of appropriate treatment are critical determinants to promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in electrochemical affinity biosensors have demonstrated to surpass conventional standards in regards to time, simplicity, accuracy and cost in this field. The tremendous potential offered by electrochemical affinity biosensors to detect on-site infectious pathogens at clinically relevant levels in scarcely treated body fluids is clearly stated in this review. The development and application of selected examples using different specific receptors, assay formats and electrochemical approaches focusing on the determination of specific circulating biomarkers of different molecular (genetic, regulatory and functional) levels associated with bacterial and viral pathogens are critically discussed. Existing challenges still to be addressed and future directions in this rapidly advancing and highly interesting field are also briefly pointed out.

ROS open roads to roundworm infection.

PubMed

Feng, Baomin; Shan, Libo

2014-04-08

The rapid production of reactive oxygen species (ROS) upon pathogen attack is generally considered a defense mechanism for microbial killing and an initiation of host defense responses in plants and animals. In this issue, Siddique et al. show that nicotinamide adenine dinucleotide phosphate oxidase-derived ROS function as a pathogenicity factor to promote the roundworm nematode infection in Arabidopsis thaliana, revealing the complex action of ROS in host-pathogen interactions.

Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of Legionella pneumophila

PubMed Central

Nogueira, Catarina V.; Lindsten, Tullia; Jamieson, Amanda M.; Case, Christopher L.; Shin, Sunny; Thompson, Craig B.; Roy, Craig R.

2009-01-01

Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication. PMID:19521510

MESSENGER Observations of Rapid and Impulsive Magnetic Reconnection in Mercury's Magnetotail

NASA Astrophysics Data System (ADS)

Zhong, J.; Wei, Y.; Pu, Z. Y.; Wang, X. G.; Wan, W. X.; Slavin, J. A.; Cao, X.; Raines, J. M.; Zhang, H.; Xiao, C. J.; Du, A. M.; Wang, R. S.; Dewey, R. M.; Chai, L. H.; Rong, Z. J.; Li, Y.

2018-06-01

The nature of magnetic reconnection in planetary magnetospheres may differ between various planets. We report the first observations of a rapidly evolving magnetic reconnection process in Mercury’s magnetotail by the MESSENGER spacecraft. The reconnection process was initialized in the plasma sheet and then evolved into the lobe region during a ∼35 s period. The tailward reconnection fronts of primary and secondary flux ropes with clear Hall signatures and energetic electron bursts were observed. The reconnection timescale of a few seconds is substantially shorter than that of terrestrial magnetospheric plasmas. The normalized reconnection rate during a brief quasi-steady period is estimated to be ∼0.2 on average. The observations show the rapid and impulsive nature of the exceedingly driven reconnection in Mercury’s magnetospheric plasma that may be responsible for the much more dynamic magnetosphere of Mercury.

Strain-Level Metagenomic Analysis of the Fermented Dairy Beverage Nunu Highlights Potential Food Safety Risks.

PubMed

Walsh, Aaron M; Crispie, Fiona; Daari, Kareem; O'Sullivan, Orla; Martin, Jennifer C; Arthur, Cornelius T; Claesson, Marcus J; Scott, Karen P; Cotter, Paul D

2017-08-15

The rapid detection of pathogenic strains in food products is essential for the prevention of disease outbreaks. It has already been demonstrated that whole-metagenome shotgun sequencing can be used to detect pathogens in food but, until recently, strain-level detection of pathogens has relied on whole-metagenome assembly, which is a computationally demanding process. Here we demonstrated that three short-read-alignment-based methods, i.e., MetaMLST, PanPhlAn, and StrainPhlAn, could accurately and rapidly identify pathogenic strains in spinach metagenomes that had been intentionally spiked with Shiga toxin-producing Escherichia coli in a previous study. Subsequently, we employed the methods, in combination with other metagenomics approaches, to assess the safety of nunu, a traditional Ghanaian fermented milk product that is produced by the spontaneous fermentation of raw cow milk. We showed that nunu samples were frequently contaminated with bacteria associated with the bovine gut and, worryingly, we detected putatively pathogenic E. coli and Klebsiella pneumoniae strains in a subset of nunu samples. Ultimately, our work establishes that short-read-alignment-based bioinformatics approaches are suitable food safety tools, and we describe a real-life example of their utilization. IMPORTANCE Foodborne pathogens are responsible for millions of illnesses each year. Here we demonstrate that short-read-alignment-based bioinformatics tools can accurately and rapidly detect pathogenic strains in food products by using shotgun metagenomics data. The methods used here are considerably faster than both traditional culturing methods and alternative bioinformatics approaches that rely on metagenome assembly; therefore, they can potentially be used for more high-throughput food safety testing. Overall, our results suggest that whole-metagenome sequencing can be used as a practical food safety tool to prevent diseases or to link outbreaks to specific food products. Copyright © 2017 American Society for Microbiology.

The Current Status of Instructional Design Theories in Relation to Today's Authoring Systems

ERIC Educational Resources Information Center

O'Neil, A. Fred

2008-01-01

It is of course very difficult to accurately project important characteristics of the future state of any rapidly evolving field, and the field of authoring systems for computer-assisted instruction (CAI) is no exception. However, strong trends in evolving CAI systems of today would seem to indicate some important characteristics of the software…

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

PubMed

Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

2014-07-15

Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule.

Behavioral Immunity Suppresses an Epizootic in Caribbean Spiny Lobsters.

PubMed

Butler, Mark J; Behringer, Donald C; Dolan, Thomas W; Moss, Jessica; Shields, Jeffrey D

2015-01-01

Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of "behavioral immunity"; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We capitalized on a "natural experiment" in which a die-off of sponges in the Florida Keys (USA) resulted in a loss of shelters for juvenile lobsters over a ~2500km2 region. Lobsters were thus concentrated in the few remaining shelters, presumably increasing their exposure to the contagious virus. Despite this spatial reorganization of the population, viral prevalence in lobsters remained unchanged after the sponge die-off and for years thereafter. A field experiment in which we introduced either a healthy or PaV1-infected lobster into lobster aggregations in natural dens confirmed that spiny lobsters practice behavioral immunity. Healthy lobsters vacated dens occupied by PaV1-infected lobsters despite the scarcity of alternative shelters and the higher risk of predation they faced when searching for a new den. Simulations from a spatially-explicit, individual-based model confirmed our empirical results, demonstrating the efficacy of behavioral immunity in preventing epizootics in this system.

Behavioral Immunity Suppresses an Epizootic in Caribbean Spiny Lobsters

PubMed Central

Butler, Mark J.; Behringer, Donald C.; Dolan, Thomas W.; Moss, Jessica; Shields, Jeffrey D.

2015-01-01

Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of “behavioral immunity”; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We capitalized on a "natural experiment" in which a die-off of sponges in the Florida Keys (USA) resulted in a loss of shelters for juvenile lobsters over a ~2500km2 region. Lobsters were thus concentrated in the few remaining shelters, presumably increasing their exposure to the contagious virus. Despite this spatial reorganization of the population, viral prevalence in lobsters remained unchanged after the sponge die-off and for years thereafter. A field experiment in which we introduced either a healthy or PaV1-infected lobster into lobster aggregations in natural dens confirmed that spiny lobsters practice behavioral immunity. Healthy lobsters vacated dens occupied by PaV1-infected lobsters despite the scarcity of alternative shelters and the higher risk of predation they faced when searching for a new den. Simulations from a spatially-explicit, individual-based model confirmed our empirical results, demonstrating the efficacy of behavioral immunity in preventing epizootics in this system. PMID:26061629

Genetic characterisation and phylogenetic analysis of PCV2 isolates from India: indications for emergence of natural inter-genotypic recombinants.

PubMed

Anoopraj, R; Rajkhowa, Tridib K; Cherian, Susan; Arya, Rahul S; Tomar, Neelam; Gupta, Ashish; Ray, Pradeep K; Somvanshi, R; Saikumar, G

2015-04-01

Porcine circovirus type 2 (PCV2), the necessary agent in pathogenesis of porcine circovirus diseases (PCVDs), has a worldwide distribution and is considered as one of the most important emerging viral pathogens of economic importance. PCV2 has been divided into four major genotypes namely PCV2a with five clusters or subtypes (2A-2E), PCV2b with three clusters (1A-1C), PCV2c and PCV2d, based on capsid (cap) gene analysis. PCV2 genome is rapidly evolving through events of recombination and mutation. Though, PCV2a was the predominant genotype initially, PCV2b shared majority of PCV2 sequences submitted to GenBank since 2003. In India, data regarding molecular characterisation of PCV2 is scant or absent. In the present study, we thoroughly analysed genetic heterogeneity of PCV2 strains circulating in Indian pig population. The results revealed that pigs in this region harboured PCV2 viruses of different genotypes including PCV2a-2D, PCV2b-1C and PCV2d. More interestingly, two isolates (PCV2Izn-89-13 and PCV2Izn-218-13) were classified as recombinant strains. Further detailed analysis suggested that these strains evolved from inter-genotypic recombination between PCV2a-2C and PCV2b-1C genotypes within cap gene. This study reports for the first time, the emergence of recombinant PCV2 strains in the Indian pig population. Copyright © 2015 Elsevier B.V. All rights reserved.

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.

PubMed

Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, María; Galán, Jorge E

2016-02-10

Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome sequence of Plasmopara viticola and insight into the pathogenic mechanism

PubMed Central

Yin, Ling; An, Yunhe; Qu, Junjie; Li, Xinlong; Zhang, Yali; Dry, Ian; Wu, Huijuan; Lu, Jiang

2017-01-01

Plasmopara viticola causes downy mildew disease of grapevine which is one of the most devastating diseases of viticulture worldwide. Here we report a 101.3 Mb whole genome sequence of P. viticola isolate ‘JL-7-2’ obtained by a combination of Illumina and PacBio sequencing technologies. The P. viticola genome contains 17,014 putative protein-coding genes and has ~26% repetitive sequences. A total of 1,301 putative secreted proteins, including 100 putative RXLR effectors and 90 CRN effectors were identified in this genome. In the secretome, 261 potential pathogenicity genes and 95 carbohydrate-active enzymes were predicted. Transcriptional analysis revealed that most of the RXLR effectors, pathogenicity genes and carbohydrate-active enzymes were significantly up-regulated during infection. Comparative genomic analysis revealed that P. viticola evolved independently from the Arabidopsis downy mildew pathogen Hyaloperonospora arabidopsidis. The availability of the P. viticola genome provides a valuable resource not only for comparative genomic analysis and evolutionary studies among oomycetes, but also enhance our knowledge on the mechanism of interactions between this biotrophic pathogen and its host. PMID:28417959

Strategies for new and improved vaccines against ticks and tick-borne diseases.

PubMed

de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C

2016-12-01

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.

Money for microbes-Pathogen avoidance and out-group helping behaviour.

PubMed

Laakasuo, Michael; Köbis, Nils; Palomäki, Jussi; Jokela, Markus

2017-02-23

Humans have evolved various adaptations against pathogens, including the physiological immune system. However, not all of these adaptations are physiological: the cognitive mechanisms whereby we avoid potential sources of pathogens-for example, disgust elicited by uncleanliness-can be considered as parts of a behavioural immune system (BIS). The mechanisms of BIS extend also to inter-group relations: Pathogen cues have been shown to increase xenophobia/ethnocentrism, as people prefer to keep their societal in-group norms unaltered and "clean." Nonetheless, little is known how pathogen cues influence people's willingness to provide humanitarian aid to out-group members. We examined how pathogen cues affected decisions of providing humanitarian aid in either instrumental (sending money) or non-instrumental form (sending personnel to help, or accepting refugees), and whether these effects were moderated by individual differences in BIS sensitivity. Data were collected in two online studies (Ns: 188 and 210). When the hypothetical humanitarian crisis involved a clear risk of infection, participants with high BIS sensitivity preferred to send money rather than personnel or to accept refugees. The results suggest that pathogen cues influence BIS-sensitive individuals' willingness to provide humanitarian aid when there is a risk of contamination to in-group members. © 2017 International Union of Psychological Science.

SIMULTANEOUS CONCENTRATION AND REAL-TIME DETECTION OF MULTIPLE CLASSES OF MICROBIAL PATHOGENS FROM DRINKING WATER

EPA Science Inventory

Key CCL viruses will be rapidly detected at low levels in water samples concentrated by a rapid HFUF or a new thin-sheet (TSM) electropositive filter adsorption-elution method and compared with the approved EPA method (1MDS VIRADEL). A unified and rapid virus concentration, n...

Chromatin versus pathogens: the function of epigenetics in plant immunity

PubMed Central

Ding, Bo; Wang, Guo-Liang

2015-01-01

To defend against pathogens, plants have developed a sophisticated innate immunity that includes effector recognition, signal transduction, and rapid defense responses. Recent evidence has demonstrated that plants utilize the epigenetic control of gene expression to fine-tune their defense when challenged by pathogens. In this review, we highlight the current understanding of the molecular mechanisms of histone modifications (i.e., methylation, acetylation, and ubiquitination) and chromatin remodeling that contribute to plant immunity against pathogens. Functions of key histone-modifying and chromatin remodeling enzymes are discussed. PMID:26388882

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

PubMed

Kurian, Allison W; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Hawley, Sarah T; Morrow, Monica; McLeod, M Chandler; Jagsi, Reshma; Katz, Steven J

2017-07-10

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

The knottin-like Blufensin family regulates genes involved in nuclear import and the secretory pathway in barley-powdery mildew interactions

USDA-ARS?s Scientific Manuscript database

Plants have evolved complex regulatory mechanisms to control a multi-layered defense response to microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSINs, small knottin-like...

Methicillin-Resistant "Staphylococcus aureus" on Campus: A New Challenge to College Health

ERIC Educational Resources Information Center

Weiner, H. Richard

2008-01-01

As new drugs to control bacterial pathogens are developed, the organisms evolve to survive. "Staphylococcus aureus", a common organism, has steadily developed resistance to antibiotics. For more than 40 years, resistant "S. aureus" presented a formidable problem to hospitalized patients; in the past decade, however, it has begun to appear outside…

Various antibiotic alternative strategies to reduce pathogen-induced inflammation and to maintain gut homeostasis in broiler chickens

USDA-ARS?s Scientific Manuscript database

The gut represents a continuously evolving ecosystem consisting of trillions of commensal bacteria living in symbiosis with the host. This host-microbe interplay plays a crucial role in physiological development and health of the host. There is increasing evidence that shows a dynamic interaction b...

Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens.

PubMed

Shaffer, J Scott; Moore, Penny L; Kardar, Mehran; Chakraborty, Arup K

2016-10-24

Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs.

Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens

PubMed Central

Shaffer, J. Scott; Moore, Penny L.; Kardar, Mehran; Chakraborty, Arup K.

2016-01-01

Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs. PMID:27791170

Rapidly expanding range of highly pathogenic avian influenza viruses

USDA-ARS?s Scientific Manuscript database

The recent introduction of highly pathogenic avian influenza virus (HPAIV) H5N8 into Europe and North America poses significant risks to poultry industries and wildlife populations and warrants continued and heightened vigilance. First discovered in South Korean poultry and wild birds in early 2014...

Sarcococca blight: Use of whole genome sequencing as a strategy for fungal disease diagnosis

USDA-ARS?s Scientific Manuscript database

Early and accurate diagnosis of new plant pathogens is vital for the rapid implementation of effective mitigation strategies and appropriate regulatory responses. Most commonly, pathogen identification relies on morphology and DNA marker analysis. However, for new diseases, these approaches may not...

Hyperspectral microscope imaging methods to classify gram-positive and gram-negative foodborne pathogenic bacteria

USDA-ARS?s Scientific Manuscript database

An acousto-optic tunable filter-based hyperspectral microscope imaging method has potential for identification of foodborne pathogenic bacteria from microcolony rapidly with a single cell level. We have successfully developed the method to acquire quality hyperspectral microscopic images from variou...

Classification of gram-positive and gram-negative foodborne pathogenic bacteria with hyperspectral microscope imaging

USDA-ARS?s Scientific Manuscript database

Optical method with hyperspectral microscope imaging (HMI) has potential for identification of foodborne pathogenic bacteria from microcolonies rapidly with a cell level. A HMI system that provides both spatial and spectral information could be an effective tool for analyzing spectral characteristic...

EVALUATION OF RAPID, QUANTITATIVE REAL-TIME PCR METHOD FOR ENUMERATION OF PATHOGENIC CANDIDA CELLS IN WATER

EPA Science Inventory

Quantitative Real-Time PCR (QRT-PCR) technology, incorporating fluorigenic 5' nuclease (TaqMan (trademark)) chemistry, was developed for the specific detection and quantification of six pathogenic species of Candida (C. albicans, C. tropicalis, C. krusei, C. parapsilosis, C. glab...

Stand Dynamics of Coast Redwood/Tanoak Forests Following Tanoak Decline

Treesearch

Kristen M. Waring; Kevin L. O' Hara

2007-01-01

Current threats to North American forests increasingly include exotic tree pathogens that cause extensive mortality. In California, tanoak (Lithocarpus densiflorus) mortality has increased rapidly since 1995, due to Phytophthora ramorum, believed to be an introduced pathogen. Tanoak frequently grows as a major component of redwood...

Label-free screening of foodborne Salmonella using surface plasmon resonance imaging

USDA-ARS?s Scientific Manuscript database

Since 15 pathogens cause approximately 95% of the foodborne infections, it is desirable to develop rapid and simultaneous screening methods for these major pathogens. In this study, we developed an immunoassay for Salmonella based on surface plasmon resonance imaging (SPRi). The sensor surface modif...

Demonstrating concepts of pathogenesis using effectors of Phytophthora infestans

USDA-ARS?s Scientific Manuscript database

Pathogenesis, or how pathogens cause disease, is an important concept in plant pathology. The study of pathogenesis in plant pathology has rapidly expanded and is now a significant portion of plant pathology research (especially research at the molecular level of host-pathogen interaction). With the...

A Customized DNA Microarray for Microbial Source Tracking in Environmental Systems

EPA Science Inventory

It is estimated that more than 160, 000 miles of rivers and streams in the United States are impaired due to the presence of waterborne pathogens. These pathogens typically originate from human and other animal fecal pollution sources; therefore, a rapid microbial source tracking...

IMPACTS OF ANTHROPOGENIC CHANGE ON THE ECOLOGY OF HUMAN PATHOGENS IN A EUTROPHYING ESTUARY: THE NEUSE RIVER ESTUARY

EPA Science Inventory

Approximately 75% of people in the U.S. live in coastal watersheds, with coastal urbanization and agricultural and industrial development increasing at rapid rates. Accelerating nutrient- and pathogen-enriched wastewater discharges accompanying coastal development are putting un...

Detection of foodborne pathogens using microarray technology

USDA-ARS?s Scientific Manuscript database

Assays based on the polymerase chain reaction (PCR) are now accepted methods for rapidly confirming the presence or absence of specific pathogens in foods and other types of samples. Conventional PCR requires the use of agarose gel electrophoresis to detect the PCR product; whereas, real-time PCR c...

The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences

PubMed Central

Brooks, Cory L.; Arutyunova, Elena; Lemieux, M. Joanne

2014-01-01

Pathogens have evolved a range of mechanisms to acquire iron from the host during infection. Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host glycoproteins lactoferrin and transferrin. The homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. While the mechanism behind iron acquisition from transferrin is well understood, relatively little is known regarding how iron is extracted from lactoferrin. Here, the crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein lactoferrin-binding protein B (LbpB) from the pathogen Neisseria meningitidis is reported. The structure is highly homologous to the previously determined structures of the accessory lipoprotein transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB structure with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity of iron-loaded lactoferrin. The specificity of LbpB safeguards proper delivery of iron-bound lactoferrin to the transporter lactoferrin-binding protein A (LbpA). The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region. This may provide a venue for preventing the production of the peptide by proteolysis, or directly sequestering the peptide, protecting the bacteria from the toxic effects of lactoferricin. PMID:25286931

Recent advances in the use of laser-induced breakdown spectroscopy (LIBS) as a rapid point-of-care pathogen diagnostic

NASA Astrophysics Data System (ADS)

Rehse, Steven; Trojand, Daniel; Putnam, Russell; Gillies, Derek; Woodman, Ryan; Sheikh, Khadija; Daabous, Andrew

2013-05-01

There is a well-known and urgent need in the fields of medicine, environmental health and safety, food-processing, and defense/security to develop new 21st Century technologies for the rapid and sensitive identification of bacterial pathogens. In only the last five years, the use of a real-time elemental (atomic) analysis performed with laser-induced breakdown spectroscopy (LIBS) has made tremendous progress in becoming a viable technology for rapid bacterial pathogen detection and identification. In this talk we will show how this laser-based optical emission spectroscopic technique is able to sensitively assay the elemental composition of bacterial cells in situ. We will also present the latest achievements of our lab to fully develop LIBS-based bacterial sensing including simulation of a rapid urinary tract infection diagnosis and investigation of a variety of autonomous multivariate analysis algorithms. Lastly, we will show how this technology is now ready to be transitioned from the laboratory to field-portable and potentially man-portable instrumentation. The introduction of such a technology into popular use could very well transform the field of bacterial biosensing - a market valued at approximately 10 billion/year world-wide. Funding for this project was provided in part by a Natural Sciences and Engineering Research Council of Canada Discovery Grant.