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Sample records for por moraxella catarrhalis

  1. Activity of Aristolochia bracteolata against Moraxella catarrhalis

    PubMed Central

    Khedr, Amgad I. M.; Abd AlGadir, Haidar; Takeshita, Satoshi; Shah, Mohammad Monir; Ichinose, Yoshio; Maki, Toshihide

    2014-01-01

    A bioassay-guided fractionation of methanol extract of Aristolochia bracteolata whole plant was carried out in order to evaluate its antimicrobial activity and to identify the active compounds in this extract. Antibacterial and antifungal activities of methanol extract against gram-positive, gram-negative, and fungal strains were investigated by the agar disk diffusion method. Among the strains tested, Moraxella catarrhalis and sea urchin-derived Bacillus sp. showed the highest sensitivity towards the methanol extract and hence they are used as test organisms for the bioassay-guided fractionation. From this extract, aristolochic acid 1 (AA-1) has been isolated and has showed the greatest antibacterial activity against both standard strain and clinical isolates of Moraxella catarrhalis with equal minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 25 and 50 μg/mL. Modification of the AA-1 to AA-1 methyl ester completely abolished the antibacterial activity of the compound and the piperonylic acid moiety of AA-1 which suggested that the coexistence of phenanthrene ring and free carboxylic acid is essential for AA-1 antibacterial activity. PMID:26904734

  2. Large unilateral pleural effusion secondary to Moraxella catarrhalis infection.

    PubMed

    Naha, Kushal; Prabhu, Ravindra

    2011-01-01

    A 43-year-old male with chronic kidney disease on maintenance hemodialysis presented with breathlessness, cough and right-sided abdominal pain. Examination revealed a large right-sided pleural effusion and subsequent thoracocentesis yielded an exudate. Although the fluid culture was sterile, sputum culture produced Moraxella catarrhalis. Tuberculosis was ruled out by pleural fluid analysis and pleural biopsy. Antibiotics were administered and subsequent radiograms indicated resolution of the effusion. This is a rare case of a large unilateral pleural effusion secondary to M. catarrhalis infection in a nonsmoker with no pre-existing pulmonary pathology. PMID:23393539

  3. Epidemiological typing of Moraxella catarrhalis by using DNA probes.

    PubMed Central

    Beaulieu, D; Scriver, S; Bergeron, M G; Low, D E; Parr, T R; Patterson, J E; Matlow, A; Roy, P H

    1993-01-01

    Small-fragment restriction enzyme analysis and DNA-DNA hybridization were used to compare 60 strains of Moraxella catarrhalis isolated from various geographic locations. Restriction enzyme analysis with HaeIII resulted in 46 different patterns, 7 of which were shared by more than one isolate. Hybridizations with two DNA probes resulted in 18 different patterns, 11 of which were shared by more than one isolate. Strains with the same restriction enzyme pattern always had the same hybridization pattern. However, of the 50 strains that shared the 11 hybridization patterns, 39 could be further differentiated by restriction enzyme analysis. We found that hybridization is a method that is specific for the epidemiological typing of M. catarrhalis, but because of limited sensitivity, combination with small-fragment restriction enzyme analysis may be necessary to better determine the relatedness of strains. Images PMID:8096219

  4. Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

    PubMed Central

    Singh, Birendra; Al-Jubair, Tamim; Voraganti, Chandrashekar; Andersson, Tobias; Mukherjee, Oindrilla; Su, Yu-Ching; Zipfel, Peter

    2015-01-01

    Several bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of human serum. It was recently demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n = 58) of the respiratory pathogen Moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein A2 (UspA2) and hybrid UspA2 (UspA2H) were identified as the plasminogen-binding factors in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H proteins followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) values of full-length UspA230–539 (amino acids 30 to 539 of UspA2) and full-length UspA2H50–720 for immobilized plasminogen were 4.8 × 10−8 M and 3.13 × 10−8 M, respectively, as measured by biolayer interferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/UspA2H was readily accessible for a urokinase plasminogen activator that converted the zymogen into active plasmin, as verified by the specific substrate S-2251 and a degradation assay with fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5, which consequently may contribute to reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and, hence, more efficient colonization of the host. PMID:26099590

  5. Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity.

    PubMed

    Singh, Birendra; Al-Jubair, Tamim; Voraganti, Chandrashekar; Andersson, Tobias; Mukherjee, Oindrilla; Su, Yu-Ching; Zipfel, Peter; Riesbeck, Kristian

    2015-09-01

    Several bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of human serum. It was recently demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n = 58) of the respiratory pathogen Moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein A2 (UspA2) and hybrid UspA2 (UspA2H) were identified as the plasminogen-binding factors in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H proteins followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (KD) values of full-length UspA2(30-539) (amino acids 30 to 539 of UspA2) and full-length UspA2H(50-720) for immobilized plasminogen were 4.8 × 10(-8) M and 3.13 × 10(-8) M, respectively, as measured by biolayer interferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/UspA2H was readily accessible for a urokinase plasminogen activator that converted the zymogen into active plasmin, as verified by the specific substrate S-2251 and a degradation assay with fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5, which consequently may contribute to reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and, hence, more efficient colonization of the host. PMID:26099590

  6. Community-Acquired Moraxella catarrhalis Bacteremic Pneumonia: Two Case Reports and Review of the Literature

    PubMed Central

    Ariza-Prota, Miguel Angel; Pando-Sandoval, Ana; García-Clemente, Marta; Fole-Vázquez, David; Casan, Pere

    2016-01-01

    Moraxella (formerly Branhamella) catarrhalis was discovered at the end of the nineteenth century, and for many decades it was considered to be a harmless commensal of the upper respiratory tract. It is a Gram-negative, aerobic diplococcus considered to be the third most common pathogen isolated in childhood sinusitis and otitis media and in adult chronic lower respiratory disease, as well as an etiological agent of pneumonia in immunosuppressed patients or those with chronic obstructive pulmonary disease. Moraxella catarrhalis pneumonia is rarely associated with bacteremia. Here, we present two cases of community-acquired Moraxella catarrhalis bacteremic pneumonia. PMID:26989548

  7. Study of the Moraxella Group I. Genus Moraxella and the Neisseria catarrhalis Group1

    PubMed Central

    Baumann, P.; Doudoroff, M.; Stanier, R. Y.

    1968-01-01

    A number of strains of oxidase-positive moraxellas and of neisserias related to Neisseria catarrhalis were characterized with respect to a number of nutritional and physiological properties and could be assigned to several species or species groups on the basis of their phenotypic traits. This grouping was consistent with that established by Bövre on the basis of transformation frequencies for streptomycin resistance. It is proposed to reserve the generic name Moraxella for the oxidase-positive rodshaped organisms, and a redescription of the genus is offered. Following the recent taxonomic proposals of Bövre and Henriksen, the specific name Moraxella osloensis is applied to the nutritionally unexacting strains that accumulate poly-β-hydroxybutyrate as carbon reserve. The nutritionally exacting strains are assigned to three distinct groups which can be regarded as separate species or as varieties of M. lacunata. The epithets applicable to these groups appear to be lacunata, nonliquefaciens, and bovis. The “false neisserias” could be assigned to at least three subgroups, one of which constitutes the clearly defined entity, N. catarrhalis, which could be distinguished from N. caviae and N. ovis. Images PMID:4866103

  8. Draft Genome Sequence of Moraxella catarrhalis Type Strain CCUG 353T

    PubMed Central

    Jakobsson, Hedvig E.; Gonzales-Siles, Lucia; Boulund, Fredrik; Karlsson, Roger; Sikora, Per; Kristiansson, Erik

    2016-01-01

    Moraxella catarrhalis is a Gram-negative commensal and pathogenic bacterium found in the human respiratory tract. It is associated with otitis media and respiratory tract infections. Here, we report the draft genome sequence of M. catarrhalis type strain CCUG 353T, composed of 18 contigs and a total size of 1.89 Mb. PMID:27313296

  9. Comparison of restriction enzymes for pulsed-field gel electrophoresis typing of Moraxella catarrhalis.

    PubMed

    Marti, Sara; Puig, Carmen; Domenech, Arnau; Liñares, Josefina; Ardanuy, Carmen

    2013-07-01

    NotI, the most prevalent restriction enzyme used for typing Moraxella catarrhalis, failed to digest genomic DNA from respiratory samples. An improved pulsed-field gel electrophoresis (PFGE) methodology determined SpeI as the best choice for typing this bacterial species, with a good restriction of clinical samples and a good clustering correlation with NotI. PMID:23678064

  10. Development of a LacZ-based transcriptional reporter system for use with Moraxella catarrhalis.

    PubMed

    Evans, Amanda S; Pybus, Christine; Hansen, Eric J

    2013-03-01

    The lack of a transcriptional reporter system for use in Moraxella catarrhalis has hindered studies of gene regulation in this pathogen. PCR and recombinant DNA methods were used to insert a multicloning site (MCS) and promoterless full-length Escherichia coli lacZ gene, flanked by transcriptional terminators both immediately upstream and downstream, into the M. catarrhalis recombinant plasmid pWW115. Insertion into the MCS in the newly constructed plasmid pASE222 of M. catarrhalis promoter regions controlled by either a repressor (i.e., NsrR) or activator (i.e., PhoB) yielded transcriptional fusion constructs that were appropriately responsive to signal inputs dependent on the host strain genotype, as measured quantitatively by means of a Miller β-galactosidase assay. The transcriptional reporter plasmid pASE222 should prove to be a useful tool for rapid screening of factors affecting gene expression in M. catarrhalis. PMID:23219721

  11. Molecular epidemiological characterization of respiratory isolates of Moraxella catarrhalis in a pediatric intensive care unit

    PubMed Central

    Matlow, Anne G; Low, Donald E; Paret, Gideon; Jarrett, Scott; Bohn, Desmond; Barker, Geoffrey; Boulanger, Jean; Ford-Jones, E Lee

    1992-01-01

    A perceived increase in the number of isolates of Moraxella catarrhalis from the respiratory secretions of patients intubated in the pediatric intensive care unit prompted a review of the clinical profiles of such patients and restriction enzyme analysis of the strains involved. Over two months, of 192 patients admitted to the unit, 154 were intubated. Of the 46 for whom endotracheal tube specimens were submitted to the laboratory, M catarrhalis was isolated in 12. M catarrhalis was not felt to be a significant respiratory pathogen by the attending medical staff in any of the patients from whom it was isolated. In only two patients (17%) could nosocomial acquisition be firmly invoked. Restriction enzyme analysis of the 12 strains ruled out the presence of an epidemic strain. Isolation of M catarrhalis from intubated children does not necessarily imply pathogenicity nor an outbreak situation. PMID:22514369

  12. Differential gene expression of Moraxella catarrhalis upon exposure to human serum

    PubMed Central

    de Vries, Stefan P.W.; Bootsma, Hester J.

    2014-01-01

    The complement system is an important part of the innate defense against invading pathogens (Blom et al., 2009; [1]). The ability to resist complement-mediated killing is considered to be an important virulence trait for the human-restricted respiratory tract pathogen Moraxella catarrhalis, as most disease-associated M. catarrhalis isolates are complement-resistant (Wirth et al., 2007; [2]). Here we provide a detailed overview of the experimental methods that we have used to study the molecular basis of M. catarrhalis complement-resistance by transcriptome profiling of the bacterium upon exposure to 10% normal human serum (NHS), associated with the study of de Vries et al. published in Molecular Microbiology in 2014 [3]. PMID:26484117

  13. The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues

    PubMed Central

    Singh, Birendra; Alvarado-Kristensson, Maria; Johansson, Martin; Hallgren, Oskar; Westergren-Thorsson, Gunilla; Mörgelin, Matthias

    2016-01-01

    ABSTRACT Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n = 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins. M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2 (UspA2) and UspA2H were identified as major collagen-binding receptors. M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that the M. catarrhalis UspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease. PMID:27006460

  14. Role of the Zinc Uptake ABC Transporter of Moraxella catarrhalis in Persistence in the Respiratory Tract

    PubMed Central

    Brauer, Aimee L.; Kirkham, Charmaine; Johnson, Antoinette; Koszelak-Rosenblum, Mary; Malkowski, Michael G.

    2013-01-01

    Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract. PMID:23817618

  15. Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis.

    PubMed

    Murphy, Timothy F; Kirkham, Charmaine; Johnson, Antoinette; Brauer, Aimee L; Koszelak-Rosenblum, Mary; Malkowski, Michael G

    2016-07-19

    Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M. catarrhalis in these populations. Using a genome mining approach we have identified a sulfate binding protein, CysP, of an ATP binding cassette (ABC) transporter system as a novel candidate vaccine antigen. CysP expresses epitopes on the bacterial surface and is highly conserved among strains. Immunization with CysP induces potentially protective immune responses in a murine pulmonary clearance model. In view of these features that indicate CysP is a promising vaccine antigen, we conducted further studies to elucidate its function. These studies demonstrated that CysP binds sulfate and thiosulfate ions, plays a nutritional role for the organism and functions in intracellular survival of M. catarrhalis in human respiratory epithelial cells. The observations that CysP has features of a vaccine antigen and also plays an important role in growth and survival of the organism indicate that CysP is an excellent candidate vaccine antigen to prevent M. catarrhalis otitis media and infections in adults with COPD. PMID:27265455

  16. Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen▿

    PubMed Central

    Yang, Min; Johnson, Antoinette; Murphy, Timothy F.

    2011-01-01

    Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis. PMID:21134967

  17. Assessment of complement-mediated killing of Moraxella (Branhamella) catarrhalis isolates by a simple method.

    PubMed Central

    Verduin, C M; Hol, C; Van Dijke, E; Faber, J A; Jansze, M; Verhoef, J; Van Dijk, H

    1995-01-01

    Recently, we showed that complement resistance is an important virulence factor of Moraxella (Branhamella) catarrhalis. Our study used a serum bactericidal assay to determine complement resistance in M. catarrhalis. Although the serum bactericidal assay is considered the "gold standard" for determining complement resistance, it is laborious and time-consuming and therefore not well suited for large-scale studies. Using a large number (n = 324) of M. catarrhalis isolates obtained from the sputa of patients with lower respiratory tract infections (n = 200) and young carriers (n = 124), we assessed the value of a simple "culture-and-spot" test as an alternative to the serum bactericidal assay. For both groups of isolates, the degree of concordance between the two tests used was very significant (P < 0.0001). The agreement between the two assays was estimated to be "excellent beyond chance" (as determined by Cohen's kappa test). The culture-and-spot assay is a valuable alternative to the serum bactericidal assay, not only for screening purposes as shown here but also for studying the mechanism of complement resistance in M. catarrhalis at the molecular level. PMID:7664184

  18. Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis.

    PubMed

    Gu, X X; Chen, J; Barenkamp, S J; Robbins, J B; Tsai, C M; Lim, D J; Battey, J

    1998-05-01

    Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. PMID:9573066

  19. Expression of the Oligopeptide Permease Operon of Moraxella catarrhalis Is Regulated by Temperature and Nutrient Availability.

    PubMed

    Jones, Megan M; Murphy, Timothy F

    2015-09-01

    Moraxella catarrhalis causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Together, these two conditions contribute to enormous morbidity and mortality worldwide. The oligopeptide permease (opp) ABC transport system is a nutritional virulence factor important for the utilization of peptides. The substrate binding protein OppA, which binds peptides for uptake, is a potential vaccine antigen, but little was known about the regulation of gene expression. The five opp genes oppB, oppC, oppD, oppF, and oppA are in the same open reading frame. Sequence analysis predicted two promoters, one located upstream of oppB and one within the intergenic region between oppF and oppA. We have characterized the gene cluster as an operon with two functional promoters and show that cold shock at 26°C for ≤ 0.5 h and the presence of a peptide substrate increase gene transcript levels. Additionally, the putative promoter upstream of oppA contributes to the transcription of oppA but is not influenced by the same environmental cues as the promoter upstream of oppB. We conclude that temperature and nutrient availability contribute to the regulation of the Opp system, which is an important nutritional virulence factor in M. catarrhalis. PMID:26099587

  20. Construction and Characterization of Moraxella catarrhalis Mutants Defective in Expression of Transferrin Receptors

    PubMed Central

    Luke, Nicole R.; Campagnari, Anthony A.

    1999-01-01

    We have previously reported the construction of an isogenic mutant defective in expression of OmpB1, the TbpB homologue, in Moraxella catarrhalis 7169. In this report, we have extended these studies by constructing and characterizing two new isogenic mutants in this clinical isolate. One mutant is defective in expression of TbpA, and the other mutant is defective in expression of both TbpA and TbpB. These isogenic mutants were confirmed by using PCR analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sequencing. In vitro growth studies, comparing all three mutants, demonstrated that the tbpA mutant and the tbpAB mutant were severely limited in their ability to grow with human holotransferrin as the sole source of iron. In contrast, the ompB1 (tbpB) mutant was capable of utilizing iron from human transferrin, although not to the extent of the parental strain. While affinity chromatography with human holotransferrin showed that each Tbp was capable of binding independently to transferrin, solid-phase transferrin binding studies using whole cells demonstrated that the tbpA mutant exhibited binding characteristics similar to those seen with the wild-type bacteria. However, the ompB1 (tbpB) mutant exhibited a diminished capacity for binding transferrin, and no binding was detected with the double mutant. These data suggest that the M. catarrhalis TbpA is necessary for the acquisition of iron from transferrin. In contrast, TbpB is not essential but may serve as a facilitory protein that functions to optimize this process. Together these mutants are essential to provide a more thorough understanding of iron acquisition mechanisms utilized by M. catarrhalis. PMID:10531234

  1. In Vitro Activity of ABT-773, a New Ketolide, against Recent Clinical Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

    PubMed Central

    Brueggemann, Angela B.; Doern, Gary V.; Huynh, Holly K.; Wingert, Elizabeth M.; Rhomberg, Paul R.

    2000-01-01

    The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae. ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin. PMID:10639382

  2. Enhancement of pulmonary clearance of Moraxella (Branhamella) catarrhalis following immunization with outer membrane protein CD in a mouse model.

    PubMed

    Murphy, T F; Kyd, J M; John, A; Kirkham, C; Cripps, A W

    1998-12-01

    Moraxella (Branhamella) catarrhalis is an important human respiratory tract pathogen. Outer membrane protein (OMP) CD is highly conserved among strains and has characteristics that indicate it may be an effective vaccine antigen. This study investigated the effect of immunization with OMP CD on pulmonary clearance following intratracheal challenge of mice with M. catarrhalis. Two routes of immunization were studied: mucosal immunization (intra-Peyer's patch followed by intratracheal boost) and intramuscular immunization with OMP CD. Both resulted in enhanced pulmonary clearance of M. catarrhalis compared with sham-immunized controls. Immunization with OMP CD induced specific antibodies in serum and bronchoalveolar lavage fluid and induced a specific lymphocyte proliferative response in T cells from mesenteric lymph nodes from mice mucosally immunized with OMP CD. On the basis of these results, OMP CD should undergo continued testing to determine whether it will induce a protective immune response in humans. PMID:9815219

  3. Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

    PubMed Central

    Otsuka, Taketo; Kirkham, Charmaine; Johnson, Antoinette; Jones, Megan M.

    2014-01-01

    Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-μg and 50-μg doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis. PMID:24914218

  4. ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence

    PubMed Central

    Murphy, Timothy F; Brauer, Aimee L.; Johnson, Antoinette; Kirkham, Charmaine

    2016-01-01

    Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract. PMID:27391026

  5. ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence.

    PubMed

    Murphy, Timothy F; Brauer, Aimee L; Johnson, Antoinette; Kirkham, Charmaine

    2016-01-01

    Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract. PMID:27391026

  6. Outer membrane porin M35 of Moraxella catarrhalis mediates susceptibility to aminopenicillins

    PubMed Central

    2009-01-01

    Background The outer membrane protein M35 is a conserved porin of type 1 strains of the respiratory pathogen Moraxella catarrhalis. It was previously shown that M35 is involved in the uptake of essential nutrients required for bacterial growth and for nasal colonization in mice. The aim of this study was (i) to characterize the potential roles of M35 in the host-pathogen interactions considering the known multifunctionality of porins and (ii) to characterize the degree of conservation in the phylogenetic older subpopulation (type 2) of M. catarrhalis. Results Isogenic m35 mutants of the type 1 strains O35E, 300 and 415 were tested for their antimicrobial susceptibility against 15 different agents. Differences in the MIC (Minimum Inhibitory Concentration) between wild-type and mutant strains were found for eight antibiotics. For ampicillin and amoxicillin, we observed a statistically significant 2.5 to 2.9-fold MIC increase (p < 0.03) in the m35 mutants. Immunoblot analysis demonstrated that human saliva contains anti-M35 IgA. Wild-type strains and their respective m35 mutants were indistinguishable with respect to the phenotypes of autoagglutination, serum resistance, iron acquisition from human lactoferrin, adherence to and invasion of respiratory tract epithelial cells, and proinflammatory stimulation of human monocytes. DNA sequencing of m35 from the phylogenetic subpopulation type 2 strain 287 revealed 94.2% and 92.8% identity on the DNA and amino acid levels, respectively, in comparison with type 1 strains. Conclusion The increase in MIC for ampicillin and amoxicillin, respectively, in the M35-deficient mutants indicates that this porin affects the outer membrane permeability for aminopenicillins in a clinically relevant manner. The presence of IgA antibodies in healthy human donors indicates that M35 is expressed in vivo and recognized as a mucosal antigen by the human host. However, immunoblot analysis of human saliva suggests the possibility of antigenic

  7. Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model

    PubMed Central

    Joslin, Stephanie N.; Pybus, Christine; Evans, Amanda S.; Lichaa, Flora; Brautigam, Chad A.

    2014-01-01

    Colonization of the human nasopharynx by Moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of M. catarrhalis to human bronchial epithelial (HBE) cells in vitro affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant M. catarrhalis strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate in vitro, in its ability to attach to HBE cells in vitro, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of M. catarrhalis to persist in an animal model. PMID:24643539

  8. Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis

    PubMed Central

    Verhaegh, Suzanne J. C.; Flores, Anthony R.; van Belkum, Alex; Musser, James M.; Hays, John P.

    2013-01-01

    Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (≥4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (≥4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence. PMID:23626831

  9. 1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity.

    PubMed

    Maračić, Silvija; Kraljević, Tatjana Gazivoda; Paljetak, Hana Čipčić; Perić, Mihaela; Matijašić, Mario; Verbanac, Donatella; Cetina, Mario; Raić-Malić, Silvana

    2015-12-01

    Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. Hybridization approach using environmentally friendly Cu(I)-catalyzed click reaction under microwave irradiation was adopted in the synthesis of regioselective 1,4-disubstituted 1,2,3-triazole tethered heterocycles (9-23 and 25-30), while post-N-alkylation of NH-1,2,3-triazoles afforded both 2,4- (31a-38a) and 1,4-disubstituted (31b-33b, 35b-37b) 1,2,3-triazole regioisomers. The compounds 18-23 and 25-30 revealed fluorescence in the violet region of the visible spectrum with a strong influence of phenyl spacer in 25-30 on both wavelength and emission intensity. Fusion of selected subunits led to new hybrid architecture, benzothiazole-1,2,3-triazole-coumarin 29 that demonstrated extremely narrow spectrum activity towards fastidious Gram-negative bacteria Moraxella catarrhalis. Selected hybrid showed the potency against Moraxella catarrhalis (MIC⩽0.25μg/mL) comparable to that of reference antibiotic azithromycin, which suggested that further investigations are necessary to optimize this potential hit compound as a new anti-Moraxella catarrhalis agent. PMID:26578325

  10. Role of the Oligopeptide Permease ABC Transporter of Moraxella catarrhalis in Nutrient Acquisition and Persistence in the Respiratory Tract

    PubMed Central

    Jones, Megan M.; Johnson, Antoinette; Koszelak-Rosenblum, Mary; Kirkham, Charmaine; Brauer, Aimee L.; Malkowski, Michael G.

    2014-01-01

    Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wild-type M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires l-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract. PMID:25156736

  11. Moraxella catarrhalis Outer Membrane Vesicles Carry β-Lactamase and Promote Survival of Streptococcus pneumoniae and Haemophilus influenzae by Inactivating Amoxicillin▿

    PubMed Central

    Schaar, Viveka; Nordström, Therése; Mörgelin, Matthias; Riesbeck, Kristian

    2011-01-01

    Moraxella catarrhalis is a common pathogen found in children with upper respiratory tract infections and in patients with chronic obstructive pulmonary disease during exacerbations. The bacterial species is often isolated together with Streptococcus pneumoniae and Haemophilus influenzae. Outer membrane vesicles (OMVs) are released by M. catarrhalis and contain phospholipids, adhesins, and immunomodulatory compounds such as lipooligosaccharide. We have recently shown that M. catarrhalis OMVs exist in patients upon nasopharyngeal colonization. As virtually all M. catarrhalis isolates are β-lactamase positive, the goal of this study was to investigate whether M. catarrhalis OMVs carry β-lactamase and to analyze if OMV consequently can prevent amoxicillin-induced killing. Recombinant β-lactamase was produced and antibodies were raised in rabbits. Transmission electron microscopy, flow cytometry, and Western blotting verified that OMVs carried β-lactamase. Moreover, enzyme assays revealed that M. catarrhalis OMVs contained active β-lactamase. OMVs (25 μg/ml) incubated with amoxicillin for 1 h completely hydrolyzed amoxicillin at concentrations up to 2.5 μg/ml. In functional experiments, preincubation of amoxicillin (10× MIC) with M. catarrhalis OMVs fully rescued amoxicillin-susceptible M. catarrhalis, S. pneumoniae, and type b or nontypeable H. influenzae from β-lactam-induced killing. Our results suggest that the presence of amoxicillin-resistant M. catarrhalis originating from β-lactamase-containing OMVs may pave the way for respiratory pathogens that by definition are susceptible to β-lactam antibiotics. PMID:21576428

  12. Comparative Genomic Analyses of the Moraxella catarrhalis Serosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution

    PubMed Central

    Earl, Joshua P.; de Vries, Stefan P.W.; Ahmed, Azad; Powell, Evan; Schultz, Matthew P.; Hermans, Peter W.M.; Hill, Darryl J.; Zhou, Zhemin; Constantinidou, Crystala I.; Hu, Fen Z.; Bootsma, Hester J.; Ehrlich, Garth D.

    2016-01-01

    The bacterial species Moraxella catarrhalis has been hypothesized as being composed of two distinct lineages (referred to as the seroresistant [SR] and serosensitive [SS]) with separate evolutionary histories based on several molecular typing methods, whereas 16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SR-lineage isolates, which revealed a relatively small supragenome when compared with other opportunistic nasopharyngeal pathogens, suggestive of a relatively short evolutionary history. Here, we performed whole-genome sequencing on 18 strains from both ribotypes of the SS lineage, an additional SR strain, as well as four previously identified highly divergent strains based on multilocus sequence typing analyses. All 35 strains were subjected to a battery of comparative genomic analyses which clearly show that there are three lineages—the SR, SS, and the divergent. The SR and SS lineages are closely related, but distinct from each other based on three different methods of comparison: Allelic differences observed among core genes; possession of lineage-specific sets of core and distributed genes; and by an alignment of concatenated core sequences irrespective of gene annotation. All these methods show that the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longer or faster than the SR lineage. There is evidence of extensive horizontal gene transfer (HGT) within both of these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these two lineages for ß-lactamase genes. The four divergent strains are sui generis, being much more distantly related to both the SR and SS groups than these other two groups are to each other. Based on average nucleotide identities, gene content, GC content, and genome size, this group could be considered as a separate

  13. Moraxella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Moraxellae are short, plump gram-negative rods, 11.5 µm X 1.5 to 2.5 mm, and are often arranged in pairs (“diplo¬ bacilli”) or short chains. The cell wall is typical of gram-negative bacteria being com¬ posed of lipopolysaccharide and protein. The lipo¬poly¬saccharide of Moraxellae does not contain ...

  14. The Vaccine Candidate Substrate Binding Protein SBP2 Plays a Key Role in Arginine Uptake, Which Is Required for Growth of Moraxella catarrhalis

    PubMed Central

    Otsuka, Taketo; Kirkham, Charmaine; Brauer, Aimee; Koszelak-Rosenblum, Mary; Malkowski, Michael G.

    2015-01-01

    Moraxella catarrhalis is an exclusively human pathogen that is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent M. catarrhalis infections would have an enormous global impact in reducing morbidity resulting from these infections. Substrate binding protein 2 (SBP2) of an ABC transporter system has recently been identified as a promising vaccine candidate antigen on the bacterial surface of M. catarrhalis. In this study, we showed that SBP1, -2, and -3 individually bind different basic amino acids with exquisite specificity. We engineered mutants that each expressed a single SBP from this gene cluster and showed in growth experiments that SBP1, -2, and -3 serve a nutritional function through acquisition of amino acids for the bacterium. SBP2 mediates uptake of arginine, a strict growth requirement of M. catarrhalis. Adherence and invasion assays demonstrated that SBP1 and SBP3 play a role in invasion of human respiratory epithelial cells, consistent with a nutritional role in intracellular survival in the human respiratory tract. This work demonstrates that the SBPs of an ABC transporter system function in the uptake of basic amino acids to support growth of M. catarrhalis. The critical role of SBP2 in arginine uptake may contribute to its potential as a vaccine antigen. PMID:26597985

  15. Use of an Isogenic Mutant Constructed in Moraxella catarrhalis To Identify a Protective Epitope of Outer Membrane Protein B1 Defined by Monoclonal Antibody 11C6

    PubMed Central

    Luke, Nicole R.; Russo, Thomas A.; Luther, Neal; Campagnari, Anthony A.

    1999-01-01

    Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds human transferrin, is OMP B1. As the human host presents a naturally iron-limited environment, proteins, like OMP B1, which are expressed in response to this nutritional stress are potential vaccine antigens. In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is the M. catarrhalis homologue to the transferrin binding protein B described for pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the surface of Escherichia coli confers transferrin binding activity, confirming that this protein is likely involved in iron acquisition. In addition, ompB1 was used to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed 7169b12, was used as the control in bactericidal assays designed to determine if OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the ompB1 isogenic mutant was resistant to this bactericidal activity. Further analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the clinical isolates tested. These data suggest that OMP B1 is a potential vaccine antigen against M. catarrhalis infections. PMID:9916077

  16. Activities of Faropenem, an Oral β-Lactam, against Recent U.S. Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

    PubMed Central

    Critchley, Ian A.; Karlowsky, James A.; Draghi, Deborah C.; Jones, Mark E.; Thornsberry, Clyde; Murfitt, Kate; Sahm, Daniel F.

    2002-01-01

    The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725 Streptococcus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 μg/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respectively; 0.5 and 1 μg/ml for β-lactamase-positive and -negative H. influenzae strains, respectively; and 0.12 and 0.5 μg/ml for β-lactamase-negative and -positive M. catarrhalis strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections. PMID:11796376

  17. Activities of faropenem, an oral beta-lactam, against recent U.S. isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

    PubMed

    Critchley, Ian A; Karlowsky, James A; Draghi, Deborah C; Jones, Mark E; Thornsberry, Clyde; Murfitt, Kate; Sahm, Daniel F

    2002-02-01

    The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725 Streptococcus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 microg/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respectively; 0.5 and 1 microg/ml for beta-lactamase-positive and -negative H. influenzae strains, respectively; and 0.12 and 0.5 microg/ml for beta-lactamase-negative and -positive M. catarrhalis strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections. PMID:11796376

  18. The Moraxella catarrhalis immunoglobulin D-binding protein MID has conserved sequences and is regulated by a mechanism corresponding to phase variation.

    PubMed

    Möllenkvist, Andrea; Nordström, Therése; Halldén, Christer; Christensen, Jens Jørgen; Forsgren, Arne; Riesbeck, Kristian

    2003-04-01

    The prevalence of the Moraxella catarrhalis immunoglobulin D (IgD)-binding outer membrane protein MID and its gene was determined in 91 clinical isolates and in 7 culture collection strains. Eighty-four percent of the clinical Moraxella strains expressed MID-dependent IgD binding. The mid gene was detected in all strains as revealed by homology of the signal peptide sequence and a conserved area in the 3' end of the gene. When MID proteins from five different strains were compared, an identity of 65.3 to 85.0% and a similarity of 71.2 to 89.1% were detected. Gene analyses showed several amino acid repeat motifs in the open reading frames, and MID could be called a putative autotransport protein. Interestingly, homopolymeric [polyguanine [poly(G)

  19. Comparative Genomic Analyses of the Moraxella catarrhalis Serosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution.

    PubMed

    Earl, Joshua P; de Vries, Stefan P W; Ahmed, Azad; Powell, Evan; Schultz, Matthew P; Hermans, Peter W M; Hill, Darryl J; Zhou, Zhemin; Constantinidou, Crystala I; Hu, Fen Z; Bootsma, Hester J; Ehrlich, Garth D

    2016-01-01

    The bacterial speciesMoraxella catarrhalishas been hypothesized as being composed of two distinct lineages (referred to as the seroresistant [SR] and serosensitive [SS]) with separate evolutionary histories based on several molecular typing methods, whereas 16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SR-lineage isolates, which revealed a relatively small supragenome when compared with other opportunistic nasopharyngeal pathogens, suggestive of a relatively short evolutionary history. Here, we performed whole-genome sequencing on 18 strains from both ribotypes of the SS lineage, an additional SR strain, as well as four previously identified highly divergent strains based on multilocus sequence typing analyses. All 35 strains were subjected to a battery of comparative genomic analyses which clearly show that there are three lineages-the SR, SS, and the divergent. The SR and SS lineages are closely related, but distinct from each other based on three different methods of comparison: Allelic differences observed among core genes; possession of lineage-specific sets of core and distributed genes; and by an alignment of concatenated core sequences irrespective of gene annotation. All these methods show that the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longer or faster than the SR lineage. There is evidence of extensive horizontal gene transfer (HGT) within both of these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these two lineages for ß-lactamase genes. The four divergent strains aresui generis, being much more distantly related to both the SR and SS groups than these other two groups are to each other. Based on average nucleotide identities, gene content, GC content, and genome size, this group could be considered as a separate

  20. Prevalence and molecular analysis of macrolide-resistant Moraxella catarrhalis clinical isolates in Japan, following emergence of the highly macrolide-resistant strain NSH1 in 2011.

    PubMed

    Kasai, Ayako; Ogihara, Shinji; Yamada, Kageto; Tanimichi, Yumiko; Nishiyama, Hiroyuki; Saito, Ryoichi

    2015-07-01

    Although Moraxella catarrhalis is known to be susceptible to macrolides, highly macrolide-resistant M. catarrhalis isolates have recently been reported in Japan and China. In this study, we investigated the prevalence of macrolide-resistant M. catarrhalis isolates in Tokyo and Chiba, Japan, and studied the mechanisms underlying their resistance. Specifically, we determined the susceptibility of 593 clinical isolates (collected between December 2011 and May 2014) to erythromycin, using the disk diffusion method. For isolates with erythromycin resistance, we identified the MICs of seven antimicrobial agents, including macrolides, and used PFGE to analyse the clonal spread. We also performed sequencing analysis to investigate macrolide-resistance targets. Thirteen isolates (2.2 %) were found to be resistant to erythromycin, showing a high MIC90 to erythromycin, clarithromycin, clindamycin and azithromycin. However, those isolates, in addition to 156 randomly selected erythromycin-susceptible strains, were susceptible to amoxicillin-clavulanate, cefixime and levofloxacin. The 13 highly macrolide-resistant isolates were classified into 10 clades and harboured three or four A2058T-mutated 23S rRNA alleles. Three highly macrolide-resistant isolates also exhibited mutations in ribosomal proteins L4 (V27A and R161C) and L22 (K68T). To the best of our knowledge, we have demonstrated for the first time that, whilst the prevalence of macrolide-resistant M. catarrhalis isolates is low in clinical settings in Japan, genetically diverse isolates with high-level macrolide resistance due to the acquisition of an A2058T mutation in the 23S rRNA have already spread. Our study therefore lays the basis for epidemiological studies of macrolide-resistant M. catarrhalis clinical isolates. PMID:25934551

  1. A Moraxella catarrhalis Two-Component Signal Transduction System Necessary for Growth in Liquid Media Affects Production of Two Lysozyme Inhibitors

    PubMed Central

    Joslin, Stephanie N.; Pybus, Christine; Labandeira-Rey, Maria; Evans, Amanda S.; Attia, Ahmed S.; Brautigam, Chad A.

    2014-01-01

    There are a paucity of data concerning gene products that could contribute to the ability of Moraxella catarrhalis to colonize the human nasopharynx. Inactivation of a gene (mesR) encoding a predicted response regulator of a two-component signal transduction system in M. catarrhalis yielded a mutant unable to grow in liquid media. This mesR mutant also exhibited increased sensitivity to certain stressors, including polymyxin B, SDS, and hydrogen peroxide. Inactivation of the gene (mesS) encoding the predicted cognate sensor (histidine) kinase yielded a mutant with the same inability to grow in liquid media as the mesR mutant. DNA microarray and real-time reverse transcriptase PCR analyses indicated that several genes previously shown to be involved in the ability of M. catarrhalis to persist in the chinchilla nasopharynx were upregulated in the mesR mutant. Two other open reading frames upregulated in the mesR mutant were shown to encode small proteins (LipA and LipB) that had amino acid sequence homology to bacterial adhesins and structural homology to bacterial lysozyme inhibitors. Inactivation of both lipA and lipB did not affect the ability of M. catarrhalis O35E to attach to a human bronchial epithelial cell line in vitro. Purified recombinant LipA and LipB fusion proteins were each shown to inhibit human lysozyme activity in vitro and in saliva. A lipA lipB deletion mutant was more sensitive than the wild-type parent strain to killing by human lysozyme in the presence of human apolactoferrin. This is the first report of the production of lysozyme inhibitors by M. catarrhalis. PMID:25312959

  2. Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from community-acquired respiratory tract infections in China: Results from the CARTIPS Antimicrobial Surveillance Program.

    PubMed

    Zhang, Yawei; Zhang, Feifei; Wang, Hui; Zhao, Chunjiang; Wang, Zhanwei; Cao, Bin; Du, Yan; Feng, Xianju; Hu, Yunjian; Hu, Bijie; Ji, Ping; Liu, Zhiyong; Liu, Yong; Liao, Wanzhen; Lu, Juan; Sun, Hongli; Wang, Zhongxin; Xu, Xiuli; Xu, Xuesong; Yang, Qing; Yu, Yunsong; Zhang, Rong; Zhuo, Chao

    2016-06-01

    This study investigated the antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates causing adult community-acquired respiratory tract infections (CARTIs) in China. A multicentre resistance surveillance study (CARTIPS) investigating 1046 clinical isolates from 19 hospitals in China was conducted from 2013 to 2014. Based on the minimum inhibitory concentration (MIC) breakpoints of oral penicillin, the percentages of penicillin-resistant, penicillin-intermediate and penicillin-susceptible S. pneumoniae were 44.1%, 13.7%, and 42.2%, respectively. The rates of penicillin-non-susceptible S. pneumoniae ranged from 27.9% to 72.2% in different cities, with the highest rate in Nanchang. Macrolides, including azithromycin, clarithromycin and erythromycin, showed the lowest activities against S. pneumoniae isolates, with resistance rates of 90.5%, 92.2% and 93.0%, respectively. However, 98% of these strains were susceptible to levofloxacin and moxifloxacin. For H. influenzae isolates, most of the antimicrobials agents exhibited good activities. However, ampicillin and trimethoprim/sulfamethoxazole showed relatively lower activity against H. influenzae, with resistance rates of 35.0% and 54.4%, respectively. β-lactamase production rates amongst H. influenzae and M. catarrhalis were 31.0% and 87.1%, respectively. In addition, a total of 15 β-lactamase-negative ampicillin-resistant (BLNAR) strains identified in this study were resistant to ampicillin, amoxicillin/clavulanic acid, cefaclor and cefuroxime. Most of the antimicrobial agents showed excellent activity against M. catarrhalis, with susceptibility rates of >90%. The results from the current study confirmed the regional variations in antimicrobial susceptibility of major CARTI pathogens and provided some choices for the treatment of these organisms. Continuous national surveillance of the epidemiology of CARTIs is strongly warranted in China. PMID:27436464

  3. A fusion protein derived from Moraxella catarrhalis and Neisseria meningitidis aimed for immune modulation of human B cells

    PubMed Central

    Mukherjee, Oindrilla; Singh, Birendra; Bayrak, Burcu; Jonsson, Ann-Beth; Mörgelin, Matthias; Riesbeck, Kristian

    2015-01-01

    Moraxella IgD-binding protein (MID) is a well characterized trimeric autotransporter that specifically targets the IgD of B cells. We fused the membrane anchor of the meningococcal autotransporter NhhA with the IgD-binding region of MID (aa 962–1200) to create a chimeric protein designated as NID. The aim was to use this specific targeting to provide a better vaccine candidate against meningococci, in particular serogroup B by enhancing the immunogenicity of NhhA. NID was thereafter recombinantly expressed in E. coli. The NID-expressing E. coli bound to peripheral B lymphocytes that resulted in cellular activation. Furthermore, we also successfully expressed NID on outer membrane vesicles, nanoparticles that are commonly used in meningococcal vaccines. This study thus highlights the applicability of the menigococcal-Moraxella fusion protein NID to be used for specific targeting of vaccine components to the IgD B cell receptor. PMID:26042357

  4. Moraxella catarrhalis lipooligosaccharide selectively upregulates ICAM-1 expression on human monocytes and stimulates adjacent naïve monocytes to produce TNF-alpha through cellular cross-talk.

    PubMed

    Xie, Hang; Gu, Xin-Xing

    2008-07-01

    To elucidate the role of Moraxella catarrhalis lipooligosaccharide (LOS) in otitis media with effusion (OME), the effects of LOS on adhesion antigens of human monocytes were investigated. M. catarrhalis LOS selectively enhanced intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on human monocytes by significantly increasing both the surface expression intensity and the percentage of ICAM-1(+) cells. ICAM-1 upregulation on human monocytes by the LOS required surface CD14, TLR4, NF-kappaB p65 and c-Jun N-terminal kinase (JNK) activity. Our study also revealed that the LOS-induced surface ICAM-1 expression was partially mediated through a TNF-alpha dependent autocrine mechanism and could be further augmented by lipopolysaccharide-binding protein in serum. In addition, M. catarrhalis LOS also stimulated human monocytes to produce pro-inflammatory cytokines in both TLR4- and CD14-dependent pathways. Our results also indicated that enhanced surface ICAM-1 expression on monocytes may hinder their adherence to the lung epithelial monolayer. Furthermore, the LOS-activated human monocytes secreted a significantly high level of IL-8, and could stimulate adjacent naïve monocytes to produce TNF-alpha which was partially mediated via membrane ICAM-1 and IL-8/IL-8RA. These results suggest that M. catarrhalis LOS could induce excessive middle ear inflammation through a cellular cross-talk mechanism during OME. PMID:18363879

  5. Ligand-bound structures of 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase from Moraxella catarrhalis reveal a water channel connecting to the active site for the second step of catalysis.

    PubMed

    Dhindwal, Sonali; Priyadarshini, Priyanka; Patil, Dipak N; Tapas, Satya; Kumar, Pramod; Tomar, Shailly; Kumar, Pravindra

    2015-02-01

    KdsC, the third enzyme of the 3-deoxy-D-manno-octulosonic acid (KDO) biosynthetic pathway, catalyzes a substrate-specific reaction to hydrolyze 3-deoxy-D-manno-octulosonate 8-phosphate to generate a molecule of KDO and phosphate. KdsC is a phosphatase that belongs to the C0 subfamily of the HAD superfamily. To understand the molecular basis for the substrate specificity of this tetrameric enzyme, the crystal structures of KdsC from Moraxella catarrhalis (Mc-KdsC) with several combinations of ligands, namely metal ion, citrate and products, were determined. Various transition states of the enzyme have been captured in these crystal forms. The ligand-free and ligand-bound crystal forms reveal that the binding of ligands does not cause any specific conformational changes in the active site. However, the electron-density maps clearly showed that the conformation of KDO as a substrate is different from the conformation adopted by KDO when it binds as a cleaved product. Furthermore, structural evidence for the existence of an intersubunit tunnel has been reported for the first time in the C0 subfamily of enzymes. A role for this tunnel in transferring water molecules from the interior of the tetrameric structure to the active-site cleft has been proposed. At the active site, water molecules are required for the formation of a water bridge that participates as a proton shuttle during the second step of the two-step phosphoryl-transfer reaction. In addition, as the KDO biosynthesis pathway is a potential antibacterial target, pharmacophore-based virtual screening was employed to identify inhibitor molecules for the Mc-KdsC enzyme. PMID:25664734

  6. Moraxella Catarrhalis: A Common Cause of Childhood Illnesses

    MedlinePlus

    ... Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental Disabilities Ear Nose & Throat Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth ...

  7. Connection between Trimethoprim-Sulfamethoxazole Use and Resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis▿

    PubMed Central

    Kärpänoja, Pauliina; Nyberg, Solja T.; Bergman, Miika; Voipio, Tinna; Paakkari, Pirkko; Huovinen, Pentti; Sarkkinen, Hannu

    2008-01-01

    The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates, and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998-2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results, it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence, resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring. PMID:18443116

  8. Branhamella catarrhalis: an organism gaining respect as a pathogen.

    PubMed Central

    Catlin, B W

    1990-01-01

    Branhamella catarrhalis was formerly regarded as a common, essentially harmless inhabitant of the pharynx. This misapprehension was caused, in part, by confusion with another pharyngeal resident, Neisseria cinerea. The two organisms can now be differentiated by the positive reactions of B. catarrhalis in tests for nitrate reduction and hydrolysis of tributyrin and DNase. B. catarrhalis is currently recognized as the third most frequent cause of acute otitis media and acute sinusitis in young children. It often causes acute exacerbations of chronic bronchopulmonary disease in older or immunocompromised adults and is incriminated occasionally in meningitis, endocarditis, bacteremia, conjunctivitis, keratitis, and urogenital infections. Virulence-associated factors, such as pili, capsules, outer membrane vesicles, iron acquisition proteins, histamine-synthesizing ability, resistance to the bactericidal action of normal human serum, and binding to the C1q complement component, have been identified in some strains. beta-Lactamase producing strains, first detected in 1976, have risen to approximately 75% worldwide. Thus far, however, practically all American strains of B. catarrhalis remain susceptible to alternative antibiotics. A possible selective advantage of recent isolates is their reportedly heightened tendency for adherence to oropharyngeal cells from patients with chronic bronchopulmonary disease. Images PMID:2121328

  9. Differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis

    PubMed Central

    Maboni, Grazieli; Gressler, Leticia T.; Espindola, Julia P.; Schwab, Marcelo; Tasca, Caiane; Potter, Luciana; de Vargas, Agueda Castagna

    2015-01-01

    The aim of this study was to determine the differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis. Thirty-two strains of Moraxella spp. isolated from cattle and sheep with infectious keratoconjunctivitis were tested via broth microdilution method to determine their susceptibility to ampicillin, cefoperazone, ceftiofur, cloxacillin, enrofloxacin, florfenicol, gentamicin, neomycin, oxytetracycline and penicillin. The results demonstrated that Moraxella spp. strains could be considered sensitive for most of the antimicrobials tested in this study, but differences between the antimicrobial susceptibility profiles of these three Moraxella species were found. M. bovis might differ from other species due to the higher MIC and MBC values it presented. PMID:26273272

  10. Morphogenetic expression of Moraxella bovis fimbriae (pili) in Pseudomonas aeruginosa.

    PubMed Central

    Beard, M K; Mattick, J S; Moore, L J; Mott, M R; Marrs, C F; Egerton, J R

    1990-01-01

    Type 4 fimbriae (pili) are found in a wide variety of gram-negative bacteria and are composed of small structural subunits which share significant sequence homology among different species, especially at their amino-terminal ends. Previous studies demonstrating morphogenetic expression of Bacteroides nodosus fimbriae from cloned subunit genes in Pseudomonas aeruginosa suggested that there is a common mechanism for type 4 fimbriae assembly and that the structural subunits are interchangeable (J. S. Mattick et al., J. Bacteriol. 169:33-41, 1987). Here we have examined the expression of Moraxella bovis fimbrial subunits in P. aeruginosa. M. bovis subunits were assembled into extracellular fimbriae in this host, in some cases as a homopolymer but in others as a mosaic with the indigenous subunit, indicating structural equivalence. This result contrasts with other studies in which recombinant P. aeruginosa expressing different subunits produced fimbriae composed almost exclusively of one subunit or the other (T. C. Elleman and J. E. Peterson, Mol. Microbiol. 1:377-380, 1987). Both observations can be explained by reversibility of subunit-subunit interactions at the site of assembly, with the forward equilibrium favoring chain extension between compatible subunits. Images PMID:1970564

  11. Moraxella species are primarily responsible for generating malodor in laundry.

    PubMed

    Kubota, Hiromi; Mitani, Asako; Niwano, Yu; Takeuchi, Kohei; Tanaka, Atsushi; Yamaguchi, Noriko; Kawamura, Yoshiaki; Hitomi, Jun

    2012-05-01

    Many people in Japan often detect an unpleasant odor generated from laundry that is hung to dry indoors or when using their already-dried laundry. Such an odor is often described as a "wet-and-dirty-dustcloth-like malodor" or an "acidic or sweaty odor." In this study, we isolated the major microorganisms associated with such a malodor, the major component of which has been identified as 4-methyl-3-hexenoic acid (4M3H). The isolates were identified as Moraxella osloensis by morphological observation and biochemical and phylogenetic tree analyses. M. osloensis has the potential to generate 4M3H in laundry. The bacterium is known to cause opportunistic infections but has never been known to generate a malodor in clothes. We found that M. osloensis exists at a high frequency in various living environments, particularly in laundry in Japan. The bacterium showed a high tolerance to desiccation and UV light irradiation, providing one of the possible reasons why they survive in laundry during and even after drying. PMID:22367080

  12. Moraxella Species Are Primarily Responsible for Generating Malodor in Laundry

    PubMed Central

    Mitani, Asako; Niwano, Yu; Takeuchi, Kohei; Tanaka, Atsushi; Yamaguchi, Noriko; Kawamura, Yoshiaki; Hitomi, Jun

    2012-01-01

    Many people in Japan often detect an unpleasant odor generated from laundry that is hung to dry indoors or when using their already-dried laundry. Such an odor is often described as a “wet-and-dirty-dustcloth-like malodor” or an “acidic or sweaty odor.” In this study, we isolated the major microorganisms associated with such a malodor, the major component of which has been identified as 4-methyl-3-hexenoic acid (4M3H). The isolates were identified as Moraxella osloensis by morphological observation and biochemical and phylogenetic tree analyses. M. osloensis has the potential to generate 4M3H in laundry. The bacterium is known to cause opportunistic infections but has never been known to generate a malodor in clothes. We found that M. osloensis exists at a high frequency in various living environments, particularly in laundry in Japan. The bacterium showed a high tolerance to desiccation and UV light irradiation, providing one of the possible reasons why they survive in laundry during and even after drying. PMID:22367080

  13. Antibiotic sensitivity of an Argentine strain collection of Moraxella bovis.

    PubMed

    Zielinski, G; Piscitelli, H; Perez-Monti, H; Stobbs, L A

    2000-01-01

    The antimicrobial susceptibility of 88 isolates of Moraxella bovis of Argentine origin was evaluated for 12 antimicrobials by broth microdilution procedures. The isolates had a minimum inhibitory concentration (MIC90) of < or = 0.06 microg/mL to enrofloxacin; < or = 0.12 microg/mL to ceftiofur; < or = 0.25 microg/mL to ampicillin; < or = 0.5 microg/mL to florfenicol and gentamicin; < or = 1.0 microg/mL to tilmicosin, erythromycin, and oxytetracycline; < or = 4.0 microg/mL to tylosin; < or = 8.0 microg/mL to spectinomycin; < or = 0.25/4.75 microg/mL to trimethoprim/sulfamethoxazole; and > or = 32 microg/mL to lincomycin. Modal MIC values for these antimicrobials were as follows: enrofloxacin, 0.03 microg/mL; ceftiofur, 0.06 pg/mL; ampicillin, 0.25 microg/mL; florfenicol, gentamicin, erythromycin, and oxytetracycline, 0.5 microg/mL; tilmicosin, 1.0 microg/mL; tylosin and spectinomycin, 4.0 microg/mL; lincomycin and erythromycin, 16 microg/mL; and trimethoprim/ sulfamethoxazole, < or = 0.25/4.75 microg/mL. These data show that all antimicrobials except lincomycin have MICs suggestive of sensitivity in vitro, though confirmation of clinical efficacy can only be properly assessed based on pharmacologic and/or clinical data to support the MIC values. PMID:19757583

  14. Septic Arthritis Due to Moraxella osloensis in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Wren, Melissa A; Caskey, John R; Liu, David X; Embers, Monica E

    2013-01-01

    A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus type D, and simian T-lymphotropic virus. The macaque's previous medical history included multiple occasions of swelling in the left tarsus, and trauma to the right arm and bilateral hands. In addition, the macaque had experienced osteomyelitis of the left distal tibia and rupture of the right cranial cruciate ligament that had been surgically repaired. Abnormal physical examination findings on presentation included a thin body condition, mild dehydration, and bilaterally swollen stifles that were warm to the touch, with the right stifle more severely affected. Mild instability in the left stifle was noted, and decreased range of motion and muscle atrophy were present bilaterally. Hematologic findings included marked neutrophilia and lymphopenia and moderate anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like organisms. Treatment with enrofloxacin was initiated empirically and subsequently switched to cephalexin, which over time alleviated the joint swelling and inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was made through isolation of the organism and sequencing of the 16S rDNA region. To our knowledge, this report is the first description of Moraxella osloensis septic arthritis in a rhesus macaque. PMID:24326229

  15. Minimum inhibitory concentrations of selected antimicrobial agents for Moraxella bovoculi associated with infectious bovine keratoconjunctivitis.

    PubMed

    Angelos, John A; Ball, Louise M; Byrne, Barbara A

    2011-05-01

    Infectious bovine keratoconjunctivitis (IBK) has been associated with ocular infections by Moraxella bovis, the established etiologic agent of IBK, and more recently, Moraxella bovoculi, a recently described species of Moraxella. To assist in designing rational treatment regimens for M. bovoculi infections associated with IBK, the in vitro susceptibilities of 57 M. bovoculi field isolates cultured from eyes of cattle with IBK in California from 2002 through 2007 were determined. The minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC(90)) of the following 18 antibiotics tested in the present study were: danofloxacin and enrofloxacin: ≤0.12 µg/ml; ampicillin and ceftiofur: ≤0.25 µg/ml; penicillin: 0.25 µg/ml; gentamicin: ≤1 µg/ml; chlortetracycline, oxytetracycline, and tiamulin: 1 µg/ml; florfenicol: 0.5 µg/ml; trimethoprim-sulfamethoxazole: ≤2/38 µg/ml; clindamycin: 2 µg/ml; neomycin and tilmicosin: ≤4 µg/ml; tulathromycin: 4 µg/ml; spectinomycin and tylosin: 16 µg/ml; and sulfadimethoxine: >256 µg/ml. The low MIC(90) of these M. bovoculi isolates suggests that commonly used antibiotics for treatment of IBK associated with M. bovis should also be effective against M. bovoculi. PMID:21908289

  16. Moraxella spp. isolated from field outbreaks of infectious bovine keratoconjunctivitis: a retrospective study of case submissions from 2010 to 2013.

    PubMed

    Loy, John Dustin; Brodersen, Bruce W

    2014-11-01

    Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is the most costly eye disease of cattle. The principal etiologic agent of IBK is the Gram-negative bacterium Moraxella bovis. However, there have been reports of IBK outbreaks associated with Moraxella bovoculi. A retrospective study of IBK diagnostic cases submitted from July 1, 2010 through October 31, 2013 was conducted. Included in the study were 1,042 Moraxella isolates from 1,538 swabs of lacrimal secretions collected from 282 herds from 30 U.S. states. Moraxella isolates were identified to the species level and were composed of M. bovoculi (701 isolates), M. bovis (295 isolates), Moraxella ovis (5 isolates), and other Moraxella spp. (41). Minimum inhibitory concentrations required for 90% growth inhibition (MIC90) was calculated for representative isolates. The MIC90 values for both M. bovis and M. bovoculi were as follows: ampicillin and ceftiofur: ≤0.25 µg/ml; clindamycin: 2 µg/ml; danofloxacin and enrofloxacin: ≤0.12 µg/ml; florfenicol: 0.5 µg/ml; gentamicin: 1 µg/ml; neomycin: 4 µg/ml; tulathromycin: 2 µg/ml; and tylosin: 8 µg/ml. The MIC90 values for M. bovoculi included the following: chlortetracycline: ≤0.5 µg/ml; oxytetracycline: 4 µg/ml; penicillin: 0.25 µg/ml; spectinomycin: 32 µg/ml; sulfadimethoxine: >256 µg/ml; tiamulin: 1 µg/ml; and trimethoprim-sulfamethoxazole: 4 µg/ml. For M. bovis, MIC90 values included the following: chlortetracycline and oxytetracycline: 1 µg/ml; penicillin: ≤0.12 µg/ml; spectinomycin: 16 µg/ml; sulfadimethoxine: ≤256 µg/ml; tiamulin: ≤0.5 µg/ml; and trimethoprim-sulfamethoxazole: ≤2 µg/ml. The current work describes the frequency of isolation and differences in antimicrobial sensitivity observed among Moraxella isolates from case submissions. PMID:25261461

  17. A Field Trial of a Pilated Moraxella bovis Bacterin for the Prevention of Infectious Bovine Keratoconjunctivitis

    PubMed Central

    Bateman, Kenneth G.; Leslie, Kenneth E.; Scholl, Thomas P.

    1986-01-01

    Two field trials were conducted to evaluate the efficacy of a Moraxella bovis bacterin in the control of infectious bovine keratoconjunctivitis. The bacterin did not affect the incidence of infectious bovine keratoconjunctivitis in either trial but did appear to reduce the severity of lesions, treatments required and withdrawals from pasture required in one trial. Possible reasons for the apparently contradictory results are offered. It is suggested that the bacterin may be of some value when used in conjunction with other preventive measures. PMID:17422610

  18. Characterization of pilin genes from seven serologically defined prototype strains of Moraxella bovis.

    PubMed Central

    Atwell, J L; Tennent, J M; Lepper, A W; Elleman, T C

    1994-01-01

    Numerous field isolates of Moraxella bovis have previously been classified by serological techniques into seven serogroups, each defined by homologous cross-reaction with antisera prepared against purified pili of a single prototype strain. The gene encoding pilin from each of the prototype strains has been characterized by nucleotide sequence determination. The coding sequences show extensive homology (70 to 80%) while the proximal downstream sequences show a dichotomy into nonhomologous sets. The pilin genes of three more strains were also characterized. The presence of an additional, partial pilin gene in each prototype strain was confirmed by Southern blot analysis, and the partial pilin genes from two strains of one serogroup were characterized by sequence determination. Features of the pilin gene sequences are considered in relation to pilin gene inversion and the serological variants of strains which may arise from gene inversion events. Images PMID:8051000

  19. Isolation, purification and spectrometric analysis of PSP toxins from moraxella sp., a bacterium associated with a toxic dinoflagellate

    SciTech Connect

    Boyce, S.D.; Doucette, G.J.

    1994-12-31

    Paralytic shellfish poisoning (PSP) is a seafood intoxication syndrome caused by the injestion of shellfish contaminated with toxins produced by algae known as dinoflagellates. The PSP toxins, saxitoxin and its derivatives, act to block voltage-dependent sodium channels and can cause paralysis and even death at higher doses. It is well documented that bacteria coexist with many harmful or toxic algal species, though the exact nature of the association in relation to toxin production is unknown. Recently, the bacterium Moraxella sp. was isolated from the PSP toxin producing dinoflagellate Alexandrium tamarense. Through HPLC analysis and saxitoxin receptor binding assays performed on crude bacterial extracts, it appears that Moraxella sp. is capable of producing saxitoxin and several of its derivatives. However, physical confirmation (e.g. mass spectrometry) of these results is still needed.

  20. Recombinant Moraxella bovoculi cytotoxin-ISCOM matrix adjuvanted vaccine to prevent naturally occurring infectious bovine keratoconjunctivitis

    PubMed Central

    Lane, V. Michael; Ball, Louise M.; Hess, John F.

    2010-01-01

    A randomized, blinded, controlled field trial was conducted during summer 2006 in a northern California, USA, herd of beef cattle to evaluate the efficacy of a recombinant Moraxella bovoculi cytotoxin subunit vaccine to prevent naturally occurring infectious bovine keratoconjunctivitis (IBK; pinkeye). A convenience sample comprised of 127 steers were administered a subcutaneous dose of either adjuvant alone (ISCOM matrices; control group) or recombinant M. bovoculi cytotoxin carboxy terminus adjuvanted with ISCOM matrices (MbvA group) and were boostered 21 days later. The steers were examined once weekly for 15 weeks for evidence of IBK. No significant difference in the cumulative proportion of corneal ulcerations was detected between groups. Compared to the control calves, the MbvA vaccinates had significantly higher increases in serum neutralizing titers to M. bovoculi hemolysin between week 0 and week 6. The prevalence of M. bovis isolations was higher from ulcerated eyes of calves vaccinated with MbvA as compared to control calves. Vaccination of calves against the carboxy terminus of M. bovoculi RTX toxin resulted in significant increases in serum hemolysin neutralizing titers and may modulate organism type cultured from ulcerated eyes of calves in herds where both M. bovis and M. bovoculi exist. Use of M. bovoculi antigens alone in vaccines to prevent IBK may not be beneficial in herds where IBK is associated with both M. bovoculi and M. bovis. PMID:20217228

  1. Degradation of naphthalene-2,6- and naphthalene-1,6-disulfonic acid by a Moraxella sp

    SciTech Connect

    Wittich, R.M.; Tast, H.G.; Knackmuss, H.J.

    1988-07-01

    A naphthalene-2,6-disulfonic acid (2,6NDS)-degrading Moraxella strain was isolated from an industrial sewage plant. This culture could also be adapted to naphthalene-1,6-disulfonic acid as growth substrate. Regioselective 1,2-dioxygenation effected desulfonation and catabolism to 5-sulfosalicylic acid (5SS), which also could be used a the sole carbon source. 5SS-grown cells exhibited high gentisate 1,2-dioxygenase activity. Neither 5SS- nor gentisate-grown cells oxidized 2,6NDS; therefore, 2,6NDS or an early metabolite must serve as an inducer of the initial catabolic enzymes(s).

  2. Inversion of Moraxella lacunata type 4 pilin gene sequences by a Neisseria gonorrhoeae site-specific recombinase.

    PubMed Central

    Rozsa, F W; Meyer, T F; Fussenegger, M

    1997-01-01

    A plasmid library of Neisseria gonorrhoeae sequences was screened for the ability to mediate recombinations on a sequence containing the Moraxella lacunata type 4 pilin gene invertible region in Escherichia coli. A plasmid containing the N. gonorrhoeae sequence encoding the putative recombinase (gcr) was identified and sequenced. Plasmids containing gcr were able to mediate site-specific recombinations despite a weak amino acid homology to Piv, the native M. lacunata pilin gene invertase. The gcr gene is present only in pathogenic strains of Neisseria tested; however, in our assays gene knockouts of gcr did not alter the variation of surface features that play a role in the pathogenesis of N. gonorrhoeae. PMID:9079926

  3. Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media.

    PubMed

    Karjalainen, H; Koskela, M; Luotonen, J; Herva, E; Sipilä, P

    1990-01-01

    Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question. PMID:2106760

  4. UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

    SciTech Connect

    Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

    1982-02-01

    A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance after ..gamma..-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process.

  5. Complete Genome Sequence of Moraxella osloensis Strain KMC41, a Producer of 4-Methyl-3-Hexenoic Acid, a Major Malodor Compound in Laundry.

    PubMed

    Goto, Takatsugu; Hirakawa, Hideki; Morita, Yuji; Tomida, Junko; Sato, Jun; Matsumura, Yuta; Mitani, Asako; Niwano, Yu; Takeuchi, Kohei; Kubota, Hiromi; Kawamura, Yoshiaki

    2016-01-01

    We report the complete genome sequence of Moraxella osloensis strain KMC41, isolated from laundry with malodor. The KMC41 genome comprises a 2,445,556-bp chromosome and three plasmids. A fatty acid desaturase and at least four β-oxidation-related genes putatively associated with 4-methyl-3-hexenoic acid generation were detected in the KMC41 chromosome. PMID:27445387

  6. Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with conjunctivitis versus the deep nasopharynx of asymptomatic cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or "pinkeye" in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine case...

  7. Shared antigenicity and immunogenicity of type 4 pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoaea, Dichelobacter nodosus, and Vibrio cholerae.

    PubMed

    Patel, P; Marrs, C F; Mattick, J S; Ruehl, W W; Taylor, R K; Koomey, M

    1991-12-01

    Immunoblotting with polyclonal rabbit antibodies raised against pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoeae, Dichelobacter nodosus, and Vibrio cholerae was used to demonstrate that these polypeptides display conserved antigenic and, in most cases, immunogenic determinants. These determinants appear to be localized to the highly homologous amino-terminal domains (residues 1 to 25). PMID:1682267

  8. Complete Genome Sequence of Moraxella osloensis Strain KMC41, a Producer of 4-Methyl-3-Hexenoic Acid, a Major Malodor Compound in Laundry

    PubMed Central

    Hirakawa, Hideki; Morita, Yuji; Tomida, Junko; Sato, Jun; Matsumura, Yuta; Mitani, Asako; Niwano, Yu; Takeuchi, Kohei; Kubota, Hiromi; Kawamura, Yoshiaki

    2016-01-01

    We report the complete genome sequence of Moraxella osloensis strain KMC41, isolated from laundry with malodor. The KMC41 genome comprises a 2,445,556-bp chromosome and three plasmids. A fatty acid desaturase and at least four β-oxidation-related genes putatively associated with 4-methyl-3-hexenoic acid generation were detected in the KMC41 chromosome. PMID:27445387

  9. Pilin-gene phase variation of Moraxella bovis is caused by an inversion of the pilin genes.

    PubMed Central

    Marrs, C F; Ruehl, W W; Schoolnik, G K; Falkow, S

    1988-01-01

    Moraxella bovis Epp63 can express either of two different pilin proteins, called alpha and beta. We have previously cloned and sequenced the beta-pilin gene and now report that DNAs isolated from bacteria expressing alpha pilin have hybridization patterns consistently different from those of bacteria expressing beta pilin. The phase variation between alpha- and beta-pilin gene expression appears to be associated with an inversion of about 2 kilobases of DNA, whose endpoints occur within the coding region of the expressed pilin gene. Comparisons of the beta-pilin gene sequence with those of well-studied bacterial inversion systems revealed a stretch of 58% sequence similarity (21 of 36 base pairs) between the left inverted repeat of the Salmonella typhimurium flagellar hin control region and the amino-terminal portion of the beta-pilin gene. Images PMID:2898471

  10. Amino acid sequence homology between Piv, an essential protein in site-specific DNA inversion in Moraxella lacunata, and transposases of an unusual family of insertion elements.

    PubMed Central

    Lenich, A G; Glasgow, A C

    1994-01-01

    Deletion analysis of the subcloned DNA inversion region of Moraxella lacunata indicates that Piv is the only M. lacunata-encoded factor required for site-specific inversion of the tfpQ/tfpI pilin segment. The predicted amino acid sequence of Piv shows significant homology solely with the transposases/integrases of a family of insertion sequence elements, suggesting that Piv is a novel site-specific recombinase. Images PMID:8021196

  11. Fermentation Products of Solvent Tolerant Marine Bacterium Moraxella spp. MB1 and Its Biotechnological Applications in Salicylic Acid Bioconversion

    PubMed Central

    Wahidullah, Solimabi; Naik, Deepak N.; Devi, Prabha

    2013-01-01

    As part of a proactive approach to environmental protection, emerging issues with potential impact on the environment is the subject of ongoing investigation. One emerging area of environmental research concerns pharmaceuticals like salicylic acid, which is the main metabolite of various analgesics including aspirin. It is a common component of sewage effluent and also an intermediate in the degradation pathway of various aromatic compounds which are introduced in the marine environment as pollutants. In this study, biotransformation products of salicylic acid by seaweed, Bryopsis plumosa, associated marine bacterium, Moraxella spp. MB1, have been investigated. Phenol, conjugates of phenol and hydroxy cinnamic acid derivatives (coumaroyl, caffeoyl, feruloyl and trihydroxy cinnamyl) with salicylic acid (3–8) were identified as the bioconversion products by electrospray ionization mass spectrometry. These results show that the microorganism do not degrade phenolic acid but catalyses oxygen dependent transformations without ring cleavage. The degradation of salicylic acid is known to proceed either via gentisic acid pathway or catechol pathway but this is the first report of biotransformation of salicylic acid into cinnamates, without ring cleavage. Besides cinnamic acid derivatives (9–12), metabolites produced by the bacterium include antimicrobial indole (13) and β-carbolines, norharman (14), harman (15) and methyl derivative (16), which are beneficial to the host and the environment. PMID:24391802

  12. Fermentation products of solvent tolerant marine bacterium Moraxella spp. MB1 and its biotechnological applications in salicylic acid bioconversion.

    PubMed

    Wahidullah, Solimabi; Naik, Deepak N; Devi, Prabha

    2013-01-01

    As part of a proactive approach to environmental protection, emerging issues with potential impact on the environment is the subject of ongoing investigation. One emerging area of environmental research concerns pharmaceuticals like salicylic acid, which is the main metabolite of various analgesics including aspirin. It is a common component of sewage effluent and also an intermediate in the degradation pathway of various aromatic compounds which are introduced in the marine environment as pollutants. In this study, biotransformation products of salicylic acid by seaweed, Bryopsis plumosa, associated marine bacterium, Moraxella spp. MB1, have been investigated. Phenol, conjugates of phenol and hydroxy cinnamic acid derivatives (coumaroyl, caffeoyl, feruloyl and trihydroxy cinnamyl) with salicylic acid (3-8) were identified as the bioconversion products by electrospray ionization mass spectrometry. These results show that the microorganism do not degrade phenolic acid but catalyses oxygen dependent transformations without ring cleavage. The degradation of salicylic acid is known to proceed either via gentisic acid pathway or catechol pathway but this is the first report of biotransformation of salicylic acid into cinnamates, without ring cleavage. Besides cinnamic acid derivatives (9-12), metabolites produced by the bacterium include antimicrobial indole (13) and β-carbolines, norharman (14), harman (15) and methyl derivative (16), which are beneficial to the host and the environment. PMID:24391802

  13. Injury and destruction of Moraxella-Acinetobacter in the radappertization process. Final Report Apr 78-1 May 80

    SciTech Connect

    Maxcy, R.B.; Rowley, D.B.

    1981-02-01

    Some highly radiation-resistant Moraxella-Acinetobacter (M-A) may survive the radappertization process for meat preservation, because these vegetative bacteria are more resistant than spores to radiation. They are, however, more susceptible than spores to other destructive factors. This work was to determine the effect of some environmental factors that influence the radappertization process. M-A, M. radiodurans, and B. cereus spores varied greatly in their response to changes in temperature of radiation and menstruum in which they were suspended. Available water was critical in response of vegetative cells to radiation. Salts at the level incorporated into meat for the radappertization process suppressed growth of both injured and uninjured M-A. This effect was attributed to reduction in water activity of the menstruum. Freezing and thawing of M-A indicated some destruction and some injury. The injured cells recovered during subsequent incubation. Thus, specific food products and conditions of radappertization must be considered for setting processing parameters. When all the factors of injury, destruction, and suppression of microbial growth are considered in the radappertization process, it is apparent there is little likelihood any of the low number of naturally occurring M-A cells would survive.

  14. Development of the radiation-resistant strain of Moraxella osloensis and effect of penicillin G on its growth

    NASA Astrophysics Data System (ADS)

    Lim, Sangyong; Yun, Hyejeong; Joe, Minho; Kim, Dongho

    2009-07-01

    A series of repeated exposures to γ-radiation with intervening outgrowth of survivors was used to develop radioresistant cultures of Moraxella osloensis that have been recognized as potential pathogenic microorganism. The D10 value of the radiation-resistant strain, 5.903±0.006 kGy, was increased by four-fold compared to the parent wild-type strain, 1.637±0.004 kGy. Since most strains of M. osloensis are sensitive to penicillin, we have surveyed the sensitivity of radiation-resistant strain to this antibiotic. When the optical density was monitored after the addition of penicillin G, the radioresistant strain appeared to be more resistant to only a low concentration of penicillin G (0.5 U/ml) than the parent strain. Interestingly, however, there was no apparent difference in the number of viable cells between both strains. Scanning electron microscope data showed that the resistance cells were generally larger than the parent cells, suggesting that this increase in size may cause a higher optical density of radioresistant cells. In conclusion, radiation mutation does not affect the penicillin resistance of M. osloensis.

  15. Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with infectious bovine keratoconjunctivitis versus the deep nasopharynx of asymptomatic cattle.

    PubMed

    Dickey, Aaron M; Loy, John D; Bono, James L; Smith, Timothy P L; Apley, Mike D; Lubbers, Brian V; DeDonder, Keith D; Capik, Sarah F; Larson, Robert L; White, Brad J; Blom, Jochen; Chitko-McKown, Carol G; Clawson, Michael L

    2016-01-01

    Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or "pinkeye" in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine cases and four from the deep nasopharynx of asymptomatic cattle. Isolates that originated from the eyes of IBK cases profoundly differed from those that originated from the nasopharynx of asymptomatic cattle in genome structure, gene content and polymorphism diversity and consequently placed into two distinct phylogenetic groups. These results suggest that there are genetically distinct strains of M. bovoculi that may not associate with IBK. PMID:26872821

  16. Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

    PubMed Central

    Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

    2016-01-01

    Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

  17. Effect of physiological age on radiation resistance of some bacteria that are highly radiation resistant. [Micrococcus radiodurans; Micrococcus sp. isolate C-3; Moraxella sp isolate 4; Escherichia coli

    SciTech Connect

    Keller, L.C.; Maxcy, R.B.

    1984-05-01

    Physiological age-dependent variation in radiation resistance was studied for three bacteria that are highly radiation resistant: Micrococcus radiodurans, Micrococcus sp. isolate C-3, and Moraxella sp. isolate 4. Stationary-phase cultures of M. radiodurans and isolate C-3 were much more resistant to gamma radiation than were log-phase cultures. This pattern of relative resistance was reversed for isolate 4. Resistance of isolate 4 to UV light was also greater during log phase, although heat resistance and NaCl tolerance after heat stresses were greater during stationary phase. Radiation-induced injury of isolate 4 compared with injury of Escherichia coli B suggested that the injury process, as well as the lethal process, was affected by growth phase. The hypothesis that growth rate affects radiation resistance was tested, and results were interpreted in light of the probable confounding effect of methods used to alter growth rates of bacteria. These results indicate that dose-response experiments should be designed to measure survival during the most resistant growth phase of the organism under study. The timing is particularly important when extrapolations of survival results might be made to potential irradiation processes for foods. 17 references.

  18. Activity of Faropenem against Middle Ear Fluid Pathogens from Children with Acute Otitis Media in Costa Rica and Israel▿

    PubMed Central

    Stone, Kimberley Clawson; Dagan, Ron; Arguedas, Adriano; Leibovitz, Eugene; Wang, Elaine; Echols, Roger M.; Janjic, Nebojsa; Critchley, Ian A.

    2007-01-01

    Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae, faropenem was the most active β-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes. PMID:17387157

  19. Activity of faropenem against middle ear fluid pathogens from children with acute otitis media in Costa Rica and Israel.

    PubMed

    Stone, Kimberley Clawson; Dagan, Ron; Arguedas, Adriano; Leibovitz, Eugene; Wang, Elaine; Echols, Roger M; Janjic, Nebojsa; Critchley, Ian A

    2007-06-01

    Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae, faropenem was the most active beta-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes. PMID:17387157

  20. Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

    SciTech Connect

    Nelson, O.D.

    1997-09-04

    This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

  1. Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing.

    PubMed

    Andersen, Trine Bundgaard; Hansen, Niels Bjørn; Laursen, Tomas; Weitzel, Corinna; Simonsen, Henrik Toft

    2016-05-01

    The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to a huge number of different cytochromes P450s (from 50 to several hundred within one plant). Within the eudicotyledons, PORs can be divided into two major clades, POR 1 and POR 2. Based on our own sequencing analysis and publicly available data, we have identified 45 PORs from the angiosperm order Apiales. These were subjected to a phylogenetic analysis along with 237 other publicly available (NCBI and oneKP) POR sequences found within the clade Asterids. Here, we show that the order Apiales only harbor members of the POR 2 clade, which are further divided into two distinct subclades. This is in contrast to most other eudicotyledon orders that have both POR 1 and POR 2. This suggests that through gene duplications and one gene deletion, Apiales only contain members of the POR 2 clade. Three POR 2 isoforms from Thapsia garganica L., Apiaceae, were all full-length in an Illumina root transcriptome dataset (available from the SRA at NCBI). All three genes were shown to be functional upon reconstitution into nanodiscs, confirming that none of the isoforms are pseudogenes. PMID:26854662

  2. Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

  3. Consequences of POR mutations and polymorphisms.

    PubMed

    Miller, Walter L; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M

    2011-04-10

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ∼40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ∼60%, is found on ∼28% of human alleles. A promoter polymorphism (∼8% of Asians and ∼13% of Caucasians) at -152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ∼30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  4. Consequences of POR mutations and polymorphisms

    PubMed Central

    Miller, Walter L.; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M.

    2015-01-01

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ~40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ~60%, is found on ~28% of human alleles. A promoter polymorphism (~8% of Asians and ~13% of Caucasians) at −152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ~30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically-relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  5. Desigualdades por cáncer

    Cancer.gov

    Información básica de las desigualdades en salud por cáncer en EE. UU., factores que contribuyen a la carga desproporcionada del cáncer en algunos grupos y ejemplos de desigualdades en incidencia y mortalidad entre ciertos grupos de la población.

  6. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System

    PubMed Central

    Gorasia, Dhana G.; Veith, Paul D.; Hanssen, Eric G.; Glew, Michelle D.; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C.

    2016-01-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32–36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  7. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

    PubMed

    Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

    2016-08-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  8. The in vitro effects of faropenem on lower respiratory tract pathogens isolated in the United Kingdom.

    PubMed

    Walsh, F; Amyes, A K B; Amyes, S G B

    2003-06-01

    Faropenem is a new oral penem with a structure different from current beta-lactams including carbapenems. The susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to faropenem, a macrolide, a beta-lactam, a beta-lactam/beta-lactamase inhibitor combination and two fluoroquinolones was investigated. S. pneumoniae was the most susceptible of the three species to faropenem. The MIC(90)s of faropenem against M. catarrhalis and H. influenzae were 0.5 and 1 mg/l, respectively. They were similar to amoxiclav (MIC (90)s of 0.25 and 0.5 mg/l). The quinolones showed strong activity against H. influenzae. A cluster analysis of the activities of amoxycillin and faropenem demonstrated a direct relationship between the two antimicrobial agent's activities and resistance profiles against both S. pneumoniae and H. influenzae. PMID:12791474

  9. One third of middle ear effusions from children undergoing tympanostomy tube placement had multiple bacterial pathogens

    PubMed Central

    2012-01-01

    Background Because previous studies have indicated that otitis media may be a polymicrobial disease, we prospectively analyzed middle ear effusions of children undergoing tympanostomy tube placement with multiplex polymerase chain reaction for four otopathogens. Methods Middle ear effusions from 207 children undergoing routine tympanostomy tube placement were collected and were classified by the surgeon as acute otitis media (AOM) for purulent effusions and as otitis media with effusion (OME) for non-purulent effusions. DNA was isolated from these samples and analyzed with multiplex polymerase chain reaction for Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis. Results 119 (57%) of 207 patients were PCR positive for at least one of these four organisms. 36 (30%) of the positive samples indicated the presence of more than one bacterial species. Patient samples were further separated into 2 groups based on clinical presentation at the time of surgery. Samples were categorized as acute otitis media (AOM) if pus was observed behind the tympanic membrane. If no pus was present, samples were categorized as otitis media with effusion (OME). Bacteria were identified in most of the children with AOM (87%) and half the children with OME (51%, p < 0.001). A single bacterial organism was detected in middle ear effusions from children with AOM more often than those with OME (74% versus 33%, p < 0.001). Haemophilus influenzae was the predominant single organism and caused 58% of all AOM in this study. Alloiococcus otitidis and Moraxella catarrhalis were more frequently identified in middle ear effusions than Streptococcus pneumoniae. Conclusions Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis were identified in the middle ear effusions of some patients with otitis media. Overall, we found AOM is predominantly a single organism infection and most commonly from Haemophilus

  10. Pharmacodynamic properties of faropenem demonstrated by studies of time-kill kinetics and postantibiotic effect.

    PubMed

    Boswell, F J; Andrews, J M; Wise, R

    1997-03-01

    The pharmacodynamic properties of faropenem, a new oral penem antibiotic, were investigated by studying time-kill kinetics and postantibiotic effect. Time-kill kinetics were employed against strains of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. The postantibiotic effects of faropenem were studied using strains of E. coli, S. aureus, H. influenzae and Streptococcus pneumoniae. The time-kill kinetic data demonstrated that faropenem has bactericidal activity. Faropenem exhibited a significant postantibiotic effect against all strains except H. influenzae. PMID:9096193

  11. Evaluation of pyrrolidonyl arylamidase for the identification of nonfermenting Gram-negative rods.

    PubMed

    Bombicino, Karina A; Almuzara, Marisa N; Famiglietti, Angela M R; Vay, Carlos

    2007-01-01

    To evaluate the activity of pyrrolidonyl arylamidase (PYR) for the differentiation and identification of nonfermenting gram negative rods (NFGNR), 293 isolates were tested. A 24 h culture of each test organism was prepared. From this a 108-109 cfu/mL suspension was added to 0.25 mL of sterile physiologic solution. A PYR disk was then added and the test was incubated for 30 minutes at 35-37 degrees C, at environmental atmosphere. Reading was done by adding 1 drop of cinnamaldehyde reagent. Strains of Acinetobacter baumannii, Acinetobacter haemolyticus, Alcaligenes faecalis, Bergeyella zoohelcum, Bordetella bronchiseptica, Bordetella hinzii, Brevundimonas diminuta, Brevundimonas vesicularis, Brucella ovis, Brucella spp., Brucella suis, Burkholderia cepacia complex, Moraxella catarrhalis, Moraxella lacunata, Moraxella nonliquefaciens, Moraxella osloensis, Oligella ureolytica, Pseudomonas alcaligenes, Pseudomonas mendocina, Pseudomonas pseudoalcaligenes, Pseudomonas putida, Pseudomonas stutzeri, Pseudomonas Vb3, Psychrobacter phenylpyruvicus, and Stenotrophomonas maltophilia were PYR negative. On the other hand Achromobacter piechaudii, Achromobacter denitrificans, Achromobacter xylosoxidans, Burkholderia gladioli, Chryseobacterium gleum-indologenes, Comamonas testosroni, Cupriavidus pauculus, Delftia acidovorans, Elizabethkingia meningoseptica, Myroides spp., Ochrobactrum anthropi, Pseudomonas oryzihabitans, Ralstonia pickettii, Rhizobium radiobacter, Shewanella spp., Sphingobacterium multivorum, Sphingobacterium spiritivorum, and Weeksella virosa were PYR positive. Finally, Acinetobacter lwoffii, Pseudomonas aeruginosa, Pseudomonas fluorescens, Roseomonas spp., and Sphingomonas paucimobilis-parapaucimobilis were PYR variable. PYR testing should be considered as a useful tool to facilitate the identification of NFGNR. PMID:16822636

  12. The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

    PubMed Central

    Vincent, Maxence S.; Durand, Eric; Cascales, Eric

    2016-01-01

    The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

  13. Polymerase Chain Reaction, Bacteriologic Detection and Antibiogram of Bacteria Isolated from Otitis Media with Effusion in Children, Shiraz, Iran

    PubMed Central

    Shishegar, Mahmood; Faramarzi, Abolhasan; Kazemi, Tayyebe; Bayat, Akbar; Motamedifar, Mohammad

    2011-01-01

    Background: Otitis media with effusion is one of the leading causes of hearing loss in children. Effective treatment of effusion in the middle ear requires appropriate empirical treatment and characterization of responsible pathogens. Objective of the present study was to detect pathogens in clinical samples from patients with otitis media with effusion in our area and to determine the sensitivity profile of isolated organisms to commonly used antibiotics. Methods: Sixty three samples of middle ear effusion were aseptically obtained from 36 children, who had been treated up to at least two weeks before sampling. They were analyzed using standard bacteriological and multiplex polymerase chain reaction (PCR) assays. Antibiotic susceptibility tests were also performed. Results: PCR analysis showed that DNA of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were present in 60 (95.2%) of the samples. The culture-positive effusion for Streptococcus Pneumoniae, HaemophilusInfluenzae and Moraxella catarrhalis was 34.9%. Almost all isolates of Streptococcus pneumoniaee were sensitive to ciprofloxacin and erythromycin, and none of them was sensitive to co-trimoxazole. None of H. Influenzae isolates was sensitive to erythromycin, cefixim, co-trimoxazole, ampicillin and amoxicillin. None of M. Catarrhalis isolates was sensitive to ceftriaxone, co-trimoxazole, ampicillin and amoxicillin. Conclusion: Compared with other studies using PCR method, the number of H. influenza isolates was in higher in the present study (95.2%). Antibiotic sensitivity profiles of pathogens isolated in this study were different from others. Thus, we can determine empirical antibiotic therapy based on sensitivity profile in our geographic area. PMID:23115412

  14. Nasopharyngeal vs. adenoid cultures in children undergoing adenoidectomy: prevalence of bacterial pathogens, their interactions and risk factors.

    PubMed

    Korona-Glowniak, I; Niedzielski, A; Kosikowska, U; Grzegorczyk, A; Malm, A

    2015-03-01

    Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus colonization of the adenoids and nasopharynx in 103 preschool children who underwent adenoidectomy for recurrent upper respiratory tract infections was examined. Bacterial interactions and risk factors for bacterial colonization of the nasopharynx and adenoids, separately, were analysed statistically. The prevalence of simultaneous isolation from both anatomical sites was 45·6% for S. pneumoniae, 29·1% for H. influenzae, 15·5% for M. catarrhalis and 18·4% for S. aureus. Three pathogens were significantly more frequent together from adenoid samples; nasopharyngeal swabs more often yielded a single organism, but without statistical significance. M. catarrhalis and S. aureus significantly more frequently co-existed with S. pneumoniae and H. influenzae than with each other and a positive association of S. pneumoniae and H. influenzae in adenoid samples was evident. Several differences between risk factors for nasopharyngeal and adenoid colonization by the individual pathogens were observed. We conclude that the adenoids and nasopharynx appear to differ substantially in colonization by pathogenic microbes but occurrence of H. influenzae and S. pneumoniae in the nasopharynx could be predictive of upper respiratory tract infections. PMID:25703401

  15. Identification of Porphyromonas gingivalis proteins secreted by the Por secretion system.

    PubMed

    Sato, Keiko; Yukitake, Hideharu; Narita, Yuka; Shoji, Mikio; Naito, Mariko; Nakayama, Koji

    2013-01-01

    The Gram-negative bacterium Porphyromonas gingivalis possesses a number of potential virulence factors for periodontopathogenicity. In particular, cysteine proteinases named gingipains are of interest given their abilities to degrade host proteins and process other virulence factors such as fimbriae. Gingipains are translocated on the cell surface or into the extracellular milieu by the Por secretion system (PorSS), which consists of a number of membrane or periplasmic proteins including PorK, PorL, PorM, PorN, PorO, PorP, PorQ, PorT, PorU, PorV (PG27, LptO), PorW and Sov. To identify proteins other than gingipains secreted by the PorSS, we compared the proteomes of P. gingivalis strains kgp rgpA rgpB (PorSS-proficient strain) and kgp rgpA rgpB porK (PorSS-deficient strain) using two-dimensional gel electrophoresis and peptide-mass fingerprinting. Sixteen spots representing 10 different proteins were present in the particle-free culture supernatant of the PorSS-proficient strain but were absent or faint in that of the PorSS-deficient strain. These identified proteins possessed the C-terminal domains (CTDs), which had been suggested to form the CTD protein family. These results indicate that the PorSS is used for secretion of a number of proteins other than gingipains and that the CTDs of the proteins are associated with the PorSS-dependent secretion. PMID:23075153

  16. System design description for portable 1,000 CFM exhauster Skids POR-007/Skid E and POR-008/Skid F

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    The primary purpose of the two 1,000 CFM Exhauster Skids, POR-007-SKID E and POR-008-SKID F, is to provide backup to the waste tank primary ventilation systems for tanks 241-C-106 and 241-AY-102, and the AY-102 annulus in the event of a failure during the sluicing of tank 241-C-106 and subsequent transfer of sluiced waste to 241-AY-102. This redundancy is required since both of the tank ventilation systems have been declared as Safety Class systems.

  17. Disminuyen en los Estados Unidos las infecciones por VPH.

    Cancer.gov

    La infección por los tipos del virus del papiloma humano (VPH) en el blanco de la vacuna cuadrivalente se redujo en casi dos tercios en las adolescentes desde que se recomendó la vacunación en los Estados Unidos.

  18. Centros oncológicos designados por el NCI

    Cancer.gov

    El programa de centros oncológicos designados por el Instituto Nacional del Cáncer (NCI) reconoce a los centros de todo el país que cumplen con rigurosos criterios para participar en proyectos avanzados de primer nivel para la investigación multidisciplinaria del cáncer.

  19. Erythromycin in acute laryngitis in adults.

    PubMed

    Schalén, L; Eliasson, I; Kamme, C; Schalén, C

    1993-03-01

    Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p < or = .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self-limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function. PMID:8457123

  20. Se evitaron casi 800 000 muertes por descenso del tabaquismo

    Cancer.gov

    Programas y estrategias de control del tabaco del siglo XX fueron responsables de la prevención de más de 795 000 muertes por cáncer de pulmón en Estados Unidos de 1975 al 2000. Si todo el tabaquismo en este país hubiera cesado después de la publicación d

  1. Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils.

    PubMed

    Peak, Ian R; Chen, Adrienne; Jen, Freda E-C; Jennings, Courtney; Schulz, Benjamin L; Saunders, Nigel J; Khan, Arshad; Seifert, H Steven; Jennings, Michael P

    2016-08-01

    The bacterial pathogen Neisseria meningitidis expresses two major outer-membrane porins. PorA expression is subject to phase-variation (high frequency, random, on-off switching), and both PorA and PorB are antigenically variable between strains. PorA expression is variable and not correlated with meningococcal colonisation or invasive disease, whereas all naturally-occurring strains express PorB suggesting strong selection for expression. We have generated N. meningitidis strains lacking expression of both major porins, demonstrating that they are dispensable for bacterial growth in vitro. The porAB mutant strain has an exponential growth rate similar to the parental strain, as do the single porA or porB mutants, but the porAB mutant strain does not reach the same cell density in stationary phase. Proteomic analysis suggests that the double mutant strain exhibits compensatory expression changes in proteins associated with cellular redox state, energy/nutrient metabolism, and membrane stability. On solid media, there is obvious growth impairment that is rescued by addition of blood or serum from mammalian species, particularly heme. These porin mutants are not impaired in their capacity to inhibit both staurosporine-induced apoptosis and a phorbol 12-myristate 13-acetate-induced oxidative burst in human neutrophils suggesting that the porins are not the only bacterial factors that can modulate these processes in host cells. PMID:26562068

  2. Compton imaging with the PorGamRays spectrometer

    NASA Astrophysics Data System (ADS)

    Judson, D. S.; Boston, A. J.; Coleman-Smith, P. J.; Cullen, D. M.; Hardie, A.; Harkness, L. J.; Jones, L. L.; Jones, M.; Lazarus, I.; Nolan, P. J.; Pucknell, V.; Rigby, S. V.; Seller, P.; Scraggs, D. P.; Simpson, J.; Slee, M.; Sweeney, A.; PorGamRays Collaboration

    2011-10-01

    The PorGamRays project aims to develop a portable gamma-ray detection system with both spectroscopic and imaging capabilities. The system is designed around a stack of thin Cadmium Zinc Telluride (CZT) detectors. The imaging capability utilises the Compton camera principle. Each detector is segmented into 100 pixels which are read out through custom designed Application Specific Integrated Circuits (ASICs). This device has potential applications in the security, decommissioning and medical fields. This work focuses on the near-field imaging performance of a lab-based demonstrator consisting of two pixelated CZT detectors, each of which is bonded to a NUCAM II ASIC. Measurements have been made with point 133Ba and 57Co sources located ˜35 mm from the surface of the scattering detector. Position resolution of ˜20 mm FWHM in the x and y planes is demonstrated.

  3. Acceptance test report for portable exhauster POR-007/Skid E

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    This document describes Acceptance Testing performed on Portable Exhauster POR-007/Skid E. It includes measurements of bearing vibration levels, pressure decay testing, programmable logic controller interlocks, high vacuum, flow and pressure control functional testing. The purpose of Acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-0490, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  4. [In vitro activity of faropenem against beta-lactamase producing clinical isolates].

    PubMed

    Nishiyama, T; Matsuzaki, K; Koyama, H; Saika, T; Hasegawa, M; Kobayashi, I

    2000-03-01

    Each 20 strains of beta-lactamase producing methicillin susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Bacteroides fragilis group were used as the test strains. Drug susceptibility of these strains to faropenem (FRPM), cefdinir, cefditoren, cefcapene, cefteram, cefaclor, and ampicillin was determined by an agar dilution method according to the NCCLS guideline M100-S9. beta-Lactamase activity of the test strains was determined by a spectrophotometric method. In the present study, FRPM was highly active against beta-lactamase-producing strains, and no close correlation was found between the MICs of FRPM for the test strains and their beta-lactamase activities. These results suggest that FRPM has potential in successful application for the treatment of infectious diseases with various types of bacterial pathogens including beta-lactamase producing strains. PMID:10834149

  5. In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.

    PubMed

    Biedenbach, D J; Bouchillon, S K; Hackel, M; Miller, L A; Scangarella-Oman, N E; Jakielaszek, C; Sahm, D F

    2016-01-01

    Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 μg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development. PMID:26729499

  6. Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

    PubMed

    Umut, S; Tutluoglu, B; Aydin Tosun, G; Müsellim, B; Erk, M; Yildirim, N; Vahapoglu, H; Yilmaz, N; Arseven, O; Türker, H; Erelel, M; Ilvan, A; Göylüsün, V; Yilmaz Kuyucu, T; Koşar, F; Soysal, F; Gür, A; Unutmaz, S; Oztürk, S; Akman, M

    1999-06-01

    Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations. PMID:10435684

  7. Microbiology of sinusitis.

    PubMed

    Brook, Itzhak

    2011-03-01

    Most sinus infections are viral, and only a small proportion develops a secondary bacterial infection. Rhinoviruses, influenza viruses, and parainfluenza viruses are the most common causes of sinusitis. The most common bacteria isolated from pediatric and adult patients with community-acquired acute purulent sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic bacteria (Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.) are the main isolates in chronic sinusitis. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are commonly isolated from patients with nosocomial sinusitis, the immunocompromised host, those with HIV infection, and in cystic fibrosis. Fungi and Pseudomonas aeruginosa are the most common isolates in neutropenic patients. The microbiology of sinusitis is influenced by the previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens. PMID:21364226

  8. Typing and surface charges of the variable loop regions of PorB from Neisseria meningitidis.

    PubMed

    Stefanelli, Paola; Neri, Arianna; Tanabe, Mikio; Fazio, Cecilia; Massari, Paola

    2016-06-01

    PorB is a pan-Neisserial major outer membrane protein with a trimeric β-barrel structure. Each monomer presents eight periplasmic turns and eight surface exposed loop regions with sequence variability. PorB induces activation of host cell responses via a TLR2-dependent mechanism likely mediated by electrostatic interactions between TLR2 and PorB surface exposed loops. Variability in the loop amino acid sequence is known to influence cell responses to PorB in vitro, particularly for the residues in L5 and L7. In this work, the sequence of the porB gene and the electrostatic surface charges of PorB from 35 invasive meningococcal isolates belonging to the main clonal complexes identified in Italy and from five carriage genomes available on the website http://pubmlst.org/neisseria/ were examined. Analysis of the porB encoding regions from the invasive meningococci has identified four new alleles and a potential association between porB alleles, serogroup, and clonal complexes. Through computer-based modeling and analysis of the electrostatic surface charges of PorB from these strains, loop charge segregation between PorB from invasive serogroups B and C was observed. Specifically, loops 1, 4, and 7 were negatively charged and L2 and L8 were mostly neutral in serogroup B isolates, while an overall homogeneous positive surface charge was present in PorB from invasive serogroup C strains. A higher PorB sequence variability was observed among carriage genomes, and a general prevalence of negative loop surface charges. The surface charge differences in PorB from serogroups B and C invasive and carriage strains may, in part, influence the outcomes of Neisseriae interactions with host cells. © 2016 IUBMB Life, 68(6):488-495, 2016. PMID:27156582

  9. Photodynamic therapy with water-soluble phtalocyanines against bacterial biofilms in teeth root canals

    NASA Astrophysics Data System (ADS)

    Gergova, Raina; Georgieva, Tzvetelina; Angelov, Ivan; Mantareva, Vanya; Valkanov, Serjoga; Mitov, Ivan; Dimitrov, Slavcho

    2012-06-01

    The study presents the PDT with metal phthalocyanines on biofilms grown in root canals of ten representatives of the Gram-positive and the Gram-negative bacterial species and a fungus Candida albicans which cause aqute teeth infections in root canals.. The extracted human single-root teeth infected for 48 h with microorganisms in conditions to form biofilms of the above pathogens were PDT treated. The stage of biofilm formation and PDT effect of the samples of the teeth were determined by the scaning electron microscopy and with standard microbial tests. The PDT treating procedure included 10 min incubation with the respected phthalocyanine and irradiated with 660 nm Diode laser for 10 min. The most strongly antibacterial activity was achieved with zinc(II) phthalocyanine (ZnPc) against Enterococcus faecalis, Staphylococcus aureus and Moraxella catarrhalis. The other Gram-negative bacteria and Candida albicans were 10-100 times more resistant than the Gram-positive species. The Gram-negative Moraxella catarrhalis and Acinetobacter baumannii were more sensitive than the enterobacteria, but eradication of Pseudomonas aeruginosa in biofilm was insignificant. The influence of the stage of biofilm formation and the initial conditions (bacterial density, photosensitizer concentration and energy fluence of radiation) to the obtained level of inactivation of biofilms was investigated. The PDT with ZnPc photosensitizers show a powerful antimicrobial activity against the most frequent pathogens in endodontic infections and this method for inactivation of pathogens may be used with sucsses for treatment of the bacterial biofilms in the root canals.

  10. Wheeze in Preschool Age Is Associated with Pulmonary Bacterial Infection and Resolves after Antibiotic Therapy

    PubMed Central

    2011-01-01

    Background Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children. Methodology/Principal Findings Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2–16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥104 colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination. Conclusions/Significance Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy. PMID:22140482

  11. Acceptance test report for portable exhauster POR-008/Skid F

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    Portable Exhauster POR-008 was procured via HNF-0490, Specification for a Portable Exhausted System for Waste Tank Ventilation. Prior to taking ownership, acceptance testing was performed at the vendors. However at the conclusion of testing a number of issues remained that required resolution before the exhausters could be used by Project W-320. The purpose of acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-O49O, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  12. [Consensus guidelines for the management of upper respiratory tract infections].

    PubMed

    Lopardo, Gustavo; Calmaggi, Aníbal; Clara, Liliana; Levy Hara, Gabriel; Mykietiuk, Analía; Pryluka, Daniel; Ruvinsky, Silvina; Vujacich, Claudia; Yahni, Diego; Bogdanowicz, Elizabeth; Klein, Manuel; López Furst, María J; Pensotti, Claudia; Rial, María J; Scapellato, Pablo

    2012-01-01

    Upper respiratory tract infections are the most common source of antibiotic prescriptions. Acute pharyngitis is caused mainly by viruses, viral cases can be distinguished from acute streptococcal pharyngitis using Centor clinical epidemiological criteria, by rapid antigen tests or throat culture. Treatment of choice for streptococcal infection is penicillin V given in two daily doses. In children, acute otitis media (AOM) is the infection for which antibiotics are most often prescribed. Predominant causative pathogens include Streptococcus pneumoniae, Haemophilus influenzae non-type b and Moraxella catarrhalis. Diagnosis is based on history, physical examination and otoscopic exam. Antibiotic treatment should be initiated promptly in all children<2 years of age, and in older children presenting bilateral AOM, otorrhoea, co-morbidities or severe illness. In Argentina, amoxicillin is the drug of choice given the low penicillin resistance rates for S. pneumoniae. In children who fail amoxicillin therapy, amoxicillin/clavulanate provides better coverage against beta-lactamase producing H. influenzae and M. catarrhalis. Rhinosinusitis is caused mainly by viruses, secondary bacterial complication occurs in less than 5% of cases. Diagnosis is based on physical examination and additional studies are not usually required. Acute bacterial sinusitis is caused by the same pathogens that cause AOM and amoxicillin is the drug of choice. PMID:23241293

  13. [Efficacy and safety of clavulanic acid/amoxicillin (1: 14) dry syrup in the treatment of children with acute bacterial rhinosinusitis].

    PubMed

    Sugita, Rinya; Yamamoto, Shuichi; Motoyama, Hidekatsu; Yarita, Masao

    2015-06-01

    To demonstrate clinical value of clavulanic acid/amoxicillin (CVA/AMPC) 1:14 combination dry syrup for acute bacterial rhinosinusitis (ABRS), the efficacy and safety were evaluated in a multicenter, open-label, uncontrolled study in 27 children with ABRS. The proportion of subjects who were 'cured' at the test of cure as the primary endpoint was 88.5%. In subjects with a major pathogenic bacteria at baseline (i.e., Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) bacterial eradication was achieved in ≥ 80% of the subjects with the exception of β-lactamase non-producing ampicillin resistant H. influenzae: BLNAR and β-lactamase producing ampicillin resistant H. influenzae: BLPAR (β-lactamase producing amoxicillin/clavulanic acid resistant H. influenzae: BLPACR). The MIC of CVA/AMPC (1:14) was not higher than 4 μg/mL for all pathogens except one strain each of BLNAR and BLPAR (BLPACR). Drug-related adverse events were reported in 19% of patients (5/27 patients). All of the reported drug-related adverse events were classified as gastrointestinal disorders that have been commonly reported with antibacterial drugs. These results indicate that CVA/AMPC (1:14) was clinically useful for the treatment of ABRS and is also suggested that was effective especially for the treatment of ABRS in children caused by beta-lactamase-producing bacteria including M. catarrhalis. PMID:26349117

  14. VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial import pathways.

    PubMed

    Müller, Anne; Rassow, Joachim; Grimm, Jan; Machuy, Nikolaus; Meyer, Thomas F; Rudel, Thomas

    2002-04-15

    The human pathogen Neisseria gonorrhoeae induces host cell apoptosis during infection by delivering the outer membrane protein PorB to the host cell's mitochondria. PorB is a pore-forming beta-barrel protein sharing several features with the mitochondrial voltage-dependent anion channel (VDAC), which is involved in the regulation of apoptosis. Here we show that PorB of pathogenic Neisseria species produced by host cells is efficiently targeted to mitochondria. Imported PorB resides in the mitochondrial outer membrane and forms multimers with similar sizes as in the outer bacterial membrane. The mitochondria completely lose their membrane potential, a characteristic previously observed in cells infected with gonococci or treated with purified PorB. Closely related bacterial porins of non-pathogenic Neisseria mucosa or Escherichia coli remain in the cytosol. Import of PorB into mitochondria in vivo is independent of a linear signal sequence. Insertion of PorB into the mitochondrial outer membrane in vitro depends on the activity of Tom5, Tom20 and Tom40, but is independent of Tom70. Our data show that human VDAC and bacterial PorB are imported into mitochondria by a similar mechanism. PMID:11953311

  15. The Viriato study: update on antimicrobial resistance of microbial pathogens responsible for community-acquired respiratory tract infections in Portugal.

    PubMed

    Melo-Cristino, José; Santos, Letícia; Silva-Costa, Catarina; Friães, Ana; Pinho, Marcos D; Ramirez, Mário

    2010-06-29

    The Viriato study is a prospective, multicentre laboratory-based surveillance study of antimicrobial susceptibility in which 30 microbiology laboratories throughout Portugal are asked to isolate, identify and submit to a central laboratory for testing Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis responsible for community-acquired lower respiratory tract infections and Streptococcus pyogenes from tonsillitis. To monitor changes in antimicrobial resistance patterns of these frequent respiratory pathogens. Susceptibility was determined by disk diffusion (Kirby-Bauer) or using Etest strips following the Clinical and Laboratory Standards Institute guidelines. From 1999 to 2007 over 13 900 isolates were analysed. Among S. pneumoniae penicillin non-susceptibility decreased from 25% in 1999 to 18% in 2007 (p = 0.002) but resistance to macrolides showed a steady increase, reaching 20% in the last 6 years. Resistance to amoxicillin and the quinolones remained stable and very low (1-2%) throughout the study period. Antimicrobial resistance among H. influenzae and M. catarrhalis remained stable. The most significant resistance was to ampicillin, of 10-12% and greater than 80%, respectively, as a result of the production of beta-lactamases. Macrolide resistance among S. pyogenes was stable during 1999-2003 (20-23%) but after 2003 there was a steady decline in resistance, which in 2007 reached 10%. The Viriato surveillance study showed that penicillin remains the most active antimicrobial agent against S. pyogenes causing tonsillitis, and amoxicillin-clavulanate and the quinolones are the most active in vitro simultaneously against S. pneumoniae, H. influenzae and M. catarrhalis responsible for community-acquired lower respiratory tract infections in Portugal. PMID:20590169

  16. Effects of Vaccination with 10-Valent Pneumococcal Non-Typeable Haemophilus influenza Protein D Conjugate Vaccine (PHiD-CV) on the Nasopharyngeal Microbiome of Kenyan Toddlers

    PubMed Central

    Feazel, Leah M.; Santorico, Stephanie A.; Robertson, Charles E.; Bashraheil, Mahfudh; Scott, J. Anthony G.

    2015-01-01

    Objective Pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. Because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). Methods Profiles of the nasopharyngeal microbiota of 60 children aged 12-59 months, who had been randomized to receive 2 doses of PHiD-CV (n=30) or Hepatitis A vaccine (n=30) 60 days apart, were constructed by 16S rRNA gene pyrosequencing of swab specimens collected before vaccination and 180 days after dose 1. Results Prior to vaccination, Moraxella catarrhalis (median of 12.3% of sequences/subject), Streptococcus pneumoniae (4.4%) and Corynebacterium spp. (5.6%) were the most abundant nasopharyngeal bacterial species. Vaccination with PHiD-CV did not significantly alter the species composition, abundance, or prevalence of known pathogens. Distinct microbiomes were identified based on the abundances of Streptococcus, Moraxella, and Haemophilus species. These microbiomes shifted in composition over the study period and were independent of age, sex, school attendance, antibiotic exposure, and vaccination. Conclusions Vaccination of children with two doses of PHiD-CV did not significantly alter the nasopharyngeal microbiome. This suggests limited replacement carriage with pathogens other than non-vaccine strains of S. pneumoniae. Trial Registration clinicaltrials.gov NCT01028326 PMID:26083474

  17. Successful Mnemonics for "por"/"para" and Affirmative Commands with Pronouns.

    ERIC Educational Resources Information Center

    Mason, Keith

    1992-01-01

    Two mnemonic devices, "4A Rule" and "PERFECT," are described to simplify the learning of two grammar points: the placement of object pronouns with respect to commands and the distinction between "por" and "para." (five references) (LB)

  18. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1.

    PubMed

    Dyson, Zoe A; Seviour, Robert J; Tucci, Joseph; Petrovski, Steve

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  19. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1

    PubMed Central

    Dyson, Zoe A.; Seviour, Robert J.; Tucci, Joseph

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa. The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  20. Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition.

    PubMed

    Kattner, Christof; Toussi, Deana N; Zaucha, Jan; Wetzler, Lee M; Rüppel, Nadine; Zachariae, Ulrich; Massari, Paola; Tanabe, Mikio

    2014-03-01

    Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling. PMID:24361688

  1. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    SciTech Connect

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T.M.

    2010-06-25

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 {angstrom} resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.

  2. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    PubMed Central

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T. M.

    2010-01-01

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 Å resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP–PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction. PMID:20351243

  3. An investigation of exploitation versus exploration in GBEA optimization of PORS 15 and 16 Problems

    SciTech Connect

    Koch, Kaelynn

    2012-01-01

    It was hypothesized that the variations in time to solution are driven by the competing mechanisms of exploration and exploitation.This thesis explores this hypothesis by examining two contrasting problems that embody the hypothesized tradeoff between exploration and exploitation. Plus one recall store (PORS) is an optimization problem based on the idea of a simple calculator with four buttons: plus, one, store, and recall. Integer addition and store are classified as operations, and one and memory recall are classified as terminals. The goal is to arrange a fixed number of keystrokes in a way that maximizes the numerical result. PORS 15 (15 keystrokes) represents the subset of difficult PORS problems and PORS 16 (16 keystrokes) represents the subset of PORS problems that are easiest to optimize. The goal of this work is to examine the tradeoff between exploitation and exploration in graph based evolutionary algorithm (GBEA) optimization. To do this, computational experiments are used to examine how solutions evolve in PORS 15 and 16 problems when solved using GBEAs. The experiment is comprised of three components; the graphs and the population, the evolutionary algorithm rule set, and the example problems. The complete, hypercube, and cycle graphs were used for this experiment. A fixed population size was used.

  4. Molecular characterisation of Porcine rubulavirus (PorPV) isolates from different outbreaks in Mexico.

    PubMed

    Cuevas-Romero, S; Rivera-Benítez, J F; Blomström, A-L; Ramliden, M; Hernández-Baumgarten, E; Hernández-Jáuregui, P; Ramírez-Mendoza, H; Berg, M

    2016-02-01

    Since the report of the initial outbreak of Porcine rubulavirus (PorPV) infection in pigs, only one full-length genome from 1984 (PorPV-LPMV/1984) has been characterised. To investigate the overall genetic variation, full-length gene nucleotide sequences of current PorPV isolates were obtained from different clinical cases of infected swine. Genome organisation and sequence analysis of the encoded proteins (NP, P, F, M, HN and L) revealed high sequence conservation of the NP protein and the expression of the P and V proteins in all PorPV isolates. The V protein of one isolate displayed a mutation that has been implicated to antagonise the antiviral immune responses of the host. The M protein indicated a variation in a short region that could affect the electrostatic charge and the interaction with the membrane. One PorPV isolate recovered from the lungs showed a mutation at the cleavage site (HRKKR) of the F protein that could represent an important factor to determine the tissue tropism and pathogenicity of this virus. The HN protein showed high sequence identity through the years (up to 2013). Additionally, a number of sequence motifs of very high amino acid conservation among the PorPV isolates important for polymerase activity of the L protein have been identified. In summary, genetic comparisons and phylogenetic analyses indicated that three different genetic variants of PorPV are currently spreading within the swine population, and a new generation of circulating virus with different characteristics has begun to emerge. PMID:26728078

  5. Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

    PubMed Central

    Shoji, Mikio; Sato, Keiko; Yukitake, Hideharu; Kondo, Yoshio; Narita, Yuka; Kadowaki, Tomoko; Naito, Mariko; Nakayama, Koji

    2011-01-01

    The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study. PMID:21731719

  6. Gliding Motility and Por Secretion System Genes Are Widespread among Members of the Phylum Bacteroidetes

    PubMed Central

    Zhu, Yongtao

    2013-01-01

    The phylum Bacteroidetes is large and diverse, with rapid gliding motility and the ability to digest macromolecules associated with many genera and species. Recently, a novel protein secretion system, the Por secretion system (PorSS), was identified in two members of the phylum, the gliding bacterium Flavobacterium johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The components of the PorSS are not similar in sequence to those of other well-studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset of the gliding motility genes, suggesting a role for the secretion system in motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is involved in secretion of gingipain protease virulence factors. Comparative analysis of 37 genomes of members of the phylum Bacteroidetes revealed the widespread occurrence of gliding motility genes and PorSS genes. Genes associated with other bacterial protein secretion systems were less common. The results suggest that gliding motility is more common than previously reported. Microscopic observations confirmed that organisms previously described as nonmotile, including Croceibacter atlanticus, “Gramella forsetii,” Paludibacter propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP-binding cassette transporter required for F. johnsoniae gliding were absent from two related gliding bacteria, suggesting that the transporter may not be central to gliding motility. PMID:23123910

  7. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    PubMed

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  8. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

    PubMed Central

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  9. An Analysis of Interlanguage Development Over Time: Part 1, "por" and "para".

    ERIC Educational Resources Information Center

    Guntermann, Gail

    1992-01-01

    The first part of a larger planned investigation, this study examines the use of "por" and "para" by nine Peace Corps volunteers in oral interviews at the end of training and roughly one year later, to trace their acquisition over time, in two learning contexts. (24 references) (LB)

  10. The Acquisition of Lexical Meaning in a Study Abroad Context: The Spanish Prepositions "por" and "para."

    ERIC Educational Resources Information Center

    Lafford, Barbara A.; Ryan, John M.

    1995-01-01

    Examination of the development of form/function relations of the prepositions "por" and "para" at different levels of proficiency in the interlanguage of study-abroad students in Granada, Spain, revealed "noncanonical" as well as "canonical" uses of these prepositions. The most common noncanonical uses were as substitutions for other prepositions…

  11. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    PubMed

    Suker, J; Feavers, I M; Achtman, M; Morelli, G; Wang, J F; Maiden, M C

    1994-04-01

    Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Translation of the gene sequences revealed a total of 19 distinct amino acid sequences in the variable regions of the protein, 6 of which were not recognized by currently available serosubtyping monoclonal antibodies. Knowledge of these amino acid sequences permitted a rational re-assignment of serosubtype names. Comparison of the complete genes with porA gene sequences from serogroup B and C meningococci showed that serogroup A possessed a limited number of the possible porA genes from a globally distributed gene pool. Each serogroup A subgroup was characterized by one of four porA gene types, probably acquired upon subgroup divergence, which was stable over periods of decades and during epidemiological spread. Comparison with other variable genes (pil and iga) indicated that the three alleles were independently assorted within the subgroup, suggesting that their gene types were older than the subgroups in which they occurred. PMID:8057850

  12. Informe a la Nación de mortalidad por cáncer sigue bajando

    Cancer.gov

    El Informe Anual a la Nación sobre el Estado del Cáncer, de 1975 a 2009, indica que los índices generales de mortalidad por cáncer siguen bajando en los Estados Unidos en hombres y mujeres, entre todos los grupos raciales y étnicos principales y para todo

  13. Detección y estudio mediante Fluorescencia Inducida por Láser de radicales libres formados por Disociación Multifotónica Infrarroja

    NASA Astrophysics Data System (ADS)

    Santos, M.; Díaz, L.; Torresano, J. A.; Rubio, L.; Samoudi, B.

    Una de las principales aplicaciones actuales de los procesos de disociación multifotónica inducidos por radiación láser infrarroja (DMI) es la producción de radiales libres, con el fin de estudiar sus propiedades cinéticas y espectroscópicas. La disociación de moléculas poliatómicas en el IR con láseres de CO2 tiene lugar desde la superficie de energía molecular mas baja y conduce generalmente a la formación de fragmentos en el estado electrónico fundamental, con diversos grados de excitación vibracional. En el Grupo de Procesos Multifotónicos del Instituto de Estructura de la Materia del C.S.I.C. hemos puesto a punto la técnica de Fluorescencia Inducida por Láser (LIF) para la detección y análisis en tiempo real de los fragmentos producidos en la DMI inducida mediante uno o dos campos láseres de diferentes longitudes de onda. Objetivos de nuestro trabajo han sido el estudio de los canales de disociación mayoritarios y de las especies transitoria producidas, así como de la distribución de energía interna con que éstas son generadas. En particular hemos detectado mediante LIF las especies: C2, CF, CH, SiH2, CF2, CH2, SiHCl, y CF3 a partir de la disociación de, entre otras, las siguientes moléculas: C2H3Br, C3F6, C4H8Si, C2H5ClSi y CH5ClSi. En este trabajo presentamos algunos de los resultados obtenidos mediante el estudio por LIF de estos radicales: estudio temporal de la señal LIF obtenida con determinación de tiempos de vida, espectros de excitación y fluorescencia, temperaturas vibracionales de formación, variación de la intensidad LIF con el tiempo de retraso entre los láseres de disociación y prueba, etc.

  14. ATP for the portable 500 CFM exhauster POR-005 skid C

    SciTech Connect

    Keller, C.M.

    1997-06-27

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-005 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  15. ATP for the portable 500 CFM exhauster POR-006 skid D

    SciTech Connect

    Keller, C.M.

    1997-07-29

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-006 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  16. ATP for the portable 500 CFM exhauster POR-004 skid B

    SciTech Connect

    Keller, C.M.

    1997-05-06

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-004 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  17. Correlation between Serological and Sequencing Analyses of the PorB Outer Membrane Protein in the Neisseria meningitidis Serotyping System

    PubMed Central

    Sacchi, Claudio T.; Lemos, Ana P. S.; Whitney, Anne M.; Solari, Claude A.; Brandt, Mary E.; Melles, Carmo E. A.; Frasch, Carl E.; Mayer, Leonard W.

    1998-01-01

    The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable. DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N. meningitidis PorB proteins (PorB VR typing). Twenty-six porB gene sequences were obtained from GenBank and aligned with 41 new sequences. Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity. We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs. The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs. These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data. The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities. Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains. In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene. PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains. The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date. PMID

  18. Zinc Finger Nuclease Knock-out of NADPH:Cytochrome P450 Oxidoreductase (POR) in Human Tumor Cell Lines Demonstrates That Hypoxia-activated Prodrugs Differ in POR Dependence*

    PubMed Central

    Su, Jiechuang; Gu, Yongchuan; Pruijn, Frederik B.; Smaill, Jeff B.; Patterson, Adam V.; Guise, Christopher P.; Wilson, William R.

    2013-01-01

    Hypoxia, a ubiquitous feature of tumors, can be exploited by hypoxia-activated prodrugs (HAP) that are substrates for one-electron reduction in the absence of oxygen. NADPH:cytochrome P450 oxidoreductase (POR) is considered one of the major enzymes responsible, based on studies using purified enzyme or forced overexpression in cell lines. To examine the role of POR in HAP activation at endogenous levels of expression, POR knock-outs were generated in HCT116 and SiHa cells by targeted mutation of exon 8 using zinc finger nucleases. Absolute quantitation by proteotypic peptide mass spectrometry of DNA sequence-confirmed multiallelic mutants demonstrated expression of proteins with residual one-electron reductase activity in some clones and identified two (Hko2 from HCT116 and S2ko1 from SiHa) that were functionally null by multiple criteria. Sensitivities of the clones to 11 HAP (six nitroaromatics, three benzotriazine N-oxides, and two quinones) were compared with wild-type and POR-overexpressing cells. All except the quinones were potentiated by POR overexpression. Knocking out POR had a marked effect on antiproliferative activity of the 5-nitroquinoline SN24349 in both genetic backgrounds after anoxic exposure but little or no effect on activity of most other HAP, including the clinical stage 2-nitroimidazole mustard TH-302, dinitrobenzamide mustard PR-104A, and benzotriazine N-oxide SN30000. Clonogenic cell killing and reductive metabolism of PR-104A and SN30000 under anoxia also showed little change in the POR knock-outs. Thus, although POR expression is a potential biomarker of sensitivity to some HAP, identification of other one-electron reductases responsible for HAP activation is needed for their rational clinical development. PMID:24196959

  19. [Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--II. Gram-negative bacteria].

    PubMed

    Suzuki, Yumiko; Nishinari, Chisato; Endo, Harumi; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2003-08-01

    The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems and carbapenems. A total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 64-time difference during the study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in antibacterial activities of CZOP against B. cepacia, and H

  20. Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem.

    PubMed

    Boswell, F J; Ashby, J P; Andrews, J M; Wise, R

    2002-10-01

    The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined. The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared. The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively. The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps. The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin. Faropenem and amoxicillin exhibited similar time-dependent kinetics. Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 x and 10 x MIC) in Iso-Sensitest broth. In 70% inactivated human serum faropenem was slowly bactericidal against M. catarrhalis, H. influenzae (one strain) and S. pneumoniae (one strain) but not group A streptococci and the other S. pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth. PMID:12356797

  1. Multistep Resistance Development Studies of Ceftaroline in Gram-Positive and -Negative Bacteria▿

    PubMed Central

    Clark, Catherine; McGhee, Pamela; Appelbaum, Peter C.; Kosowska-Shick, Klaudia

    2011-01-01

    Ceftaroline, the active component of the prodrug ceftaroline fosamil, is a novel broad-spectrum cephalosporin with bactericidal activity against Gram-positive and -negative isolates. This study evaluated the potential for ceftaroline and comparator antibiotics to select for clones of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis with elevated MICs. S. pneumoniae and S. pyogenes isolates in the present study were highly susceptible to ceftaroline (MIC range, 0.004 to 0.25 μg/ml). No streptococcal strains yielded ceftaroline clones with increased MICs (defined as an increase in MIC of >4-fold) after 50 daily passages. Ceftaroline MICs for H. influenzae and M. catarrhalis were 0.06 to 2 μg/ml for four strains and 8 μg/ml for a β-lactamase-positive, efflux-positive H. influenzae with a mutation in L22. One H. influenzae clone with an increased ceftaroline MIC (quinolone-resistant, β-lactamase-positive) was recovered after 20 days. The ceftaroline MIC for this isolate increased 16-fold, from 0.06 to 1 μg/ml. MICs for S. aureus ranged from 0.25 to 1 μg/ml. No S. aureus isolates tested with ceftaroline had clones with increased MIC (>4-fold) after 50 passages. Two E. faecalis isolates tested had ceftaroline MICs increased from 1 to 8 μg/ml after 38 days and from 4 to 32 μg/ml after 41 days, respectively. The parental ceftaroline MIC for the one K. pneumoniae extended-spectrum β-lactamase-negative isolate tested was 0.5 μg/ml and did not change after 50 daily passages. PMID:21343467

  2. Bacterial-resistance among outpatients of county hospitals in China: significant geographic distinctions and minor differences between central cities.

    PubMed

    Xiao, Yonghong; Wei, Zeqing; Shen, Ping; Ji, Jinru; Sun, Ziyong; Yu, Hua; Zhang, Tiantuo; Ji, Ping; Ni, Yuxing; Hu, Zhidong; Chu, Yunzhuo; Li, Lanjuan

    2015-06-01

    The purpose of this study was to survey antibacterial resistance in outpatients of Chinese county hospitals. A total of 31 county hospitals were selected and samples continuously collected from August 2010 to August 2011. Drug sensitivity testing was conducted in a central laboratory. A total of 2946 unique isolates were collected, including 634 strains of Escherichia coli, 606 Klebsiella pneumoniae, 476 Staphylococcus aureus, 308 Streptococcus pneumoniae, and 160 Haemophilus influenzae. Extended-spectrum β-lactamases were detected in E. coli (42.3% strains), K. pneumoniae (31.7%), and Proteus mirabilis (39.0%). Ciprofloxacin-resistance was detected in 51.0% of E. coli strains. Salmonella spp. and Shigella spp. were sensitive to most antibacterial agents. Less than 8.0% of Pseudomonas aeruginosa isolates were resistant to carbapenem. For S. aureus strains, 15.3% were resistant to methicillin, and some strains of S. pneumoniae showed resistance to penicillin (1.6%), ceftriaxone (13.0%), and erythromycin (96.4%). β-lactamase was produced by 96.5% of Moraxella catarrhalis strains, and 36.2% of H. influenzae isolates were resistant to ampicillin. Azithromycin-resistant H. influenzae, imipenem-resistant but meropenem-sensitive Proteus, and ceftriaxone- and carbapenem non-sensitive M. catarrhalis were recorded. In conclusion, cephalosporin- and quinolone-resistant strains of E. coli and Klebsiella pneumonia and macrolide-resistant Gram-positive cocci were relatively prominent in county hospitals. The antibacterial resistance profiles of isolates from different geographical locations varied significantly, with proportions in county hospitals lower than those in their tertiary counterparts in the central cities, although the difference is diminishing. PMID:25708671

  3. Activity of JNJ-Q2, a new fluoroquinolone, tested against contemporary pathogens isolated from patients with community-acquired bacterial pneumonia.

    PubMed

    Biedenbach, Douglas J; Farrell, David J; Flamm, Robert K; Liverman, Lisa C; McIntyre, Gail; Jones, Ronald N

    2012-04-01

    JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at ≤0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)≤0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development. PMID:22306239

  4. Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece.

    PubMed

    Karageorgopoulos, D E; Maraki, S; Vatopoulos, A C; Samonis, G; Schito, G C; Falagas, M E

    2013-11-01

    Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates. PMID:23686506

  5. Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

    PubMed Central

    Jones, Mark E.; Staples, Angela M.; Critchley, Ian; Thornsberry, Clyde; Heinze, Paul; Engler, Howard D.; Sahm, Daniel F.

    2000-01-01

    To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of Streptococcus pneumoniae (5,640), Haemophilus influenzae (6,583), and Moraxella catarrhalis (3,648) referred from 377 institutions during 1998 is described. For S. pneumoniae the modal MIC and MIC at which 90% of the isolates were inhibited (MIC90) for moxifloxacin were 0.12 and 0.25 μg/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations in gyrA and/or parC known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs ≥3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC90 for M. catarrhalis (both 0.06 μg/ml) and for H. influenzae (both 0.03 μg/ml) were independent of β-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies. PMID:10991838

  6. Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens.

    PubMed

    Shen, Hongwei; Zhu, Bingqing; Wang, Shulian; Mo, Haolian; Wang, Ji; Li, Jin; Zhang, Chen; Zeng, Huashu; Guan, Li; Shi, Weixian; Zhang, Yong; Ma, Xuejun

    2015-01-01

    A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP) which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1) associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs) of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from five distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR), which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, two of Klebsiella pneumoniae and one of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100, 100%, respectively), H. influenzae (92.3, 97.9%, respectively), M. pneumoniae (69.2, 99.0%, respectively), K. pneumoniae (100, 100%, respectively), and M. catarrhalis (100, 100%, respectively). Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in nine of Staphylococcus spp. and one of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics. PMID

  7. Common Cell Shape Evolution of Two Nasopharyngeal Pathogens

    PubMed Central

    Veyrier, Frédéric J.; Biais, Nicolas; Morales, Pablo; Belkacem, Nouria; Guilhen, Cyril; Ranjeva, Sylvia; Sismeiro, Odile; Péhau-Arnaudet, Gérard; Rocha, Eduardo P.; Werts, Catherine

    2015-01-01

    Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) and a cell shape change from rod to cocci had been selected for along the past evolution of N. meningitidis. Using genomic comparison across species, we correlated the emergence of the new cell shape (cocci) with the deletion, from the genome of N. meningitidis ancestor, of only one gene: yacF. Moreover, the reconstruction of this genetic deletion in a bacterium harboring the ancestral version of the locus together with the analysis of the PG structure, suggest that this gene is coordinating the transition from cell elongation to cell division. Accompanying the loss of yacF, the elongation machinery was also lost by several of the descendants leading to the change in the PG structure observed in N. meningitidis. Finally, the same evolution was observed for the ancestor of M. catarrhalis. This suggests a strong selection of these genetic events during the colonization of the nasopharynx. This selection may have been forced by the requirement of evolving permissive interaction with the immune system, the need to reduce the cellular surface exposed to immune attacks without reducing the intracellular storage capacity, or the necessity to better compete for adhesion to target cells. PMID:26162030

  8. Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro

    PubMed Central

    Mocca, Brian

    2012-01-01

    In mammalian cells, nitric oxide (NO·) is an important signal molecule with concentration-dependent and often controversial functions of promoting cell survival and inducing cell death. An inducible nitric oxide synthase (iNOS) in various mammalian cells produces higher levels of NO· from l-arginine upon infections to eliminate pathogens. In this study, we reveal novel pathogenic roles of NO· generated by bacteria in bacterium-host cell cocultures using Moraxella catarrhalis, a respiratory tract disease-causing bacterium, as a biological producer of NO·. We recently demonstrated that M. catarrhalis cells that express the nitrite reductase (AniA protein) can produce NO· by reducing nitrite. Our study suggests that, in the presence of pathophysiological levels of nitrite, this opportunistic pathogen hijacks host cell signaling and modulates host gene expression through its ability to produce NO· from nitrite. Bacterium-generated NO· significantly increases the secretion of tumor necrosis factor alpha (TNF-α) and modulates the expression of apoptotic proteins, therefore triggering host cell programmed death partially through TNF-α signaling. Furthermore, our study reveals that bacterium-generated NO· stalls host cell division and directly results in the death of dividing cells by reducing the levels of an essential regulator of cell division. This study provides unique insight into why NO· may exert more severe cytotoxic effects on fast growing cells, providing an important molecular basis for NO·-mediated pathogenesis in infections and possible therapeutic applications of NO·-releasing molecules in tumorigenesis. This study strongly suggests that bacterium-generated NO· can play important pathogenic roles during infections. PMID:22636782

  9. Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322.

    PubMed

    O'Dwyer, Karen; Hackel, Meredith; Hightower, Sarah; Hoban, Daryl; Bouchillon, Samuel; Qin, Donghui; Aubart, Kelly; Zalacain, Magdalena; Butler, Deborah

    2013-05-01

    GSK1322322 is a novel peptide deformylase (PDF) inhibitor being developed for the intravenous and oral treatment of acute bacterial skin and skin structure infections and hospitalized patients with community-acquired pneumonia. The activity of GSK1322322 was tested against a global collection of clinical isolates of Haemophilus influenzae (n = 2,370), Moraxella catarrhalis (n = 115), Streptococcus pneumoniae (n = 947), Streptococcus pyogenes (n = 617), and Staphylococcus aureus (n = 940), including strains resistant to one or more marketed antibiotics. GSK1322322 had an MIC(90) of 1 μg/ml against M. catarrhalis and 4 μg/ml against H. influenzae, with 88.8% of β-lactamase-positive strains showing growth inhibition at that concentration. All S. pneumoniae strains were inhibited by ≤ 4 μg/ml of GSK1322322, with an MIC(90) of 2 μg/ml. Pre-existing resistance mechanisms did not affect its potency, as evidenced by the MIC(90) of 1 μg/ml for penicillin, levofloxacin, and macrolide-resistant S. pneumoniae. GSK1322322 was very potent against S. pyogenes strains, with an MIC(90) of 0.5 μg/ml, irrespective of their macrolide resistance phenotype. This PDF inhibitor was also active against S. aureus strains regardless of their susceptibility to methicillin, macrolides, or levofloxacin, with an MIC(90) of 4 μg/ml in all cases. Time-kill studies showed that GSK1322322 had bactericidal activity against S. pneumoniae, H. influenzae, S. pyogenes, and S. aureus, demonstrating a ≥ 3-log(10) decrease in the number of CFU/ml at 4× MIC within 24 h in 29 of the 33 strains tested. Given the antibacterial potency demonstrated against this panel of organisms, GSK1322322 represents a valuable alternative therapy for the treatment of infectious diseases caused by drug-resistant pathogens. PMID:23478958

  10. [Antimicrobial activity of cefodizime against clinical isolates].

    PubMed

    Suzuki, Y; Ishihara, R; Ishii, Y; Nakazawa, A; Deguchi, K; Matsumoto, Y; Nishinari, C; Nakane, Y; Fukumoto, T

    1996-10-01

    In order to evaluate antimicrobial activity of cefodizime (CDZM), minimum inhibitory concentrations (MICs) of CDZM and control drugs were determined against clinical isolates collected from nation-wide medical institutions and in our laboratory from September to December of 1992 and from September to December of 1995. The results are summarized as follows: 1. Bacterial species with no or few strains resistant to CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter koseri, Proteus mirabilis and Neisseria gonorrhoeae. The range of MIC values of CDZM against Klebsiella pneumoniae was spread. Other strains, Streptococcus pneumoniae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, Providencia spp., Peptostreptococcus spp. and Bacteroides fragilis group were resistant to cephems including CDZM. 2. The MIC90's of CDZM were 0.05 approximately 3.13 micrograms/ml against Streptococcus spp., H. influenzae, M. (B.) catarrhalis, E. coli, Klebsiella spp., P. mirabilis, N. gonorrhoeae and Peptostreptococcus spp. obtained in 1995 that were frequently found in daily treatment of infections. It appears that the effectiveness of CDZM was still relatively high against community-acquired infections. 3. Among H. influenzae isolates included imipenem (IPM)-resistant and norfloxacin (NFLX)-resistant strains. The MIC-range of CDZM against strains collected in 1995 including IPM-resistant and NFLX-resistant strains was < or = 0.025 approximately 0.1 microgram/ml, and MIC90 against these strains was 0.05 microgram/ml. CDZM showed strong antimicrobial activities against H. influenzae strains resistant to carbapenems and new-quinolones. PMID:8986558

  11. Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2008: general view of the pathogens' antibacterial susceptibility.

    PubMed

    Niki, Yoshihito; Hanaki, Hideaki; Matsumoto, Tetsuya; Yagisawa, Morimasa; Kohno, Shigeru; Aoki, Nobuki; Watanabe, Akira; Sato, Junko; Hattori, Rikizo; Koashi, Naoto; Terada, Michinori; Kozuki, Tsuneo; Maruo, Akinori; Morita, Kohei; Ogasawara, Kazuhiko; Takahashi, Yoshisaburo; Matsuda, Kenji; Nakanishi, Kunio; Sunakawa, Keisuke; Takeuchi, Kenichi; Fujimura, Seiichi; Takeda, Hiroaki; Ikeda, Hideki; Sato, Naohito; Niitsuma, Katsunao; Saito, Miwako; Koshiba, Shizuko; Kaneko, Michiyo; Miki, Makoto; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Nishiya, Hajime; Kawakami, Sayoko; Aoki, Yasuko; Chonabayashi, Naohiko; Sugiura, Hideko; Ichioka, Masahiko; Goto, Hajime; Kurai, Daisuke; Saraya, Takeshi; Okazaki, Mitsuhiro; Yoshida, Koichiro; Yoshida, Takashi; Tsukada, Hiroki; Imai, Yumiko; Honma, Yasuo; Yamamoto, Toshinobu; Kawai, Atsuro; Mikamo, Hiroshige; Takesue, Yoshio; Wada, Yasunao; Miyara, Takeyuki; Toda, Hirofumi; Mitsuno, Noriko; Fujikawa, Yasunori; Nakajima, Hirokazu; Kubo, Shuichi; Ohta, Yoshio; Mikasa, Keiichi; Kasahara, Kei; Koizumi, Akira; Sano, Reiko; Yagi, Shinichi; Takaya, Mariko; Kurokawa, Yukinori; Kusano, Nobuchika; Mihara, Eiichiro; Nose, Motoko; Kuwabara, Masao; Fujiue, Yoshihiro; Ishimaru, Toshiyuki; Matsubara, Nobuo; Kawasaki, Yuji; Tokuyasu, Hirokazu; Masui, Kayoko; Kido, Masamitsu; Ota, Toshiyuki; Honda, Junichi; Kadota, Junichi; Hiramatsu, Kazufumi; Aoki, Yosuke; Nagasawa, Zenzo; Yanagihara, Katsunori; Fujita, Jiro; Tateyama, Masao; Totsuka, Kyoichi

    2011-08-01

    For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P. aeruginosa were found to be metallo

  12. Characterization of Plasmid pOR1 from Ornithobacterium rhinotracheale and Construction of a Shuttle Plasmid

    PubMed Central

    Jansen, Ruud; Chansiripornchai, Niwat; Gaastra, Wim; van Putten, Jos P. M.

    2004-01-01

    The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its mechanisms of virulence is still very limited. Here we report the development of a transformation system that enables genetic modification of O. rhinotracheale. The system is based on a cryptic plasmid, pOR1, that was derived from an O. rhinotracheale strain of serotype K. Sequencing indicated that the plasmid consisted of 14,787 nucleotides. Sequence analysis revealed one replication origin and several rep genes that control plasmid replication and copy number, respectively. In addition, pOR1 contains genes with similarity to a heavy-metal-transporting ATPase, a TonB-linked siderophore receptor, and a laccase. Reverse transcription-PCR demonstrated that these genes were transcribed. Other putative open reading frames exhibited similarities with a virulence-associated protein in Actinobacillus actinomycetemcomitans and a number of genes coding for proteins with unknown function. An Escherichia coli-O. rhinotracheale shuttle plasmid (pOREC1) was constructed by cloning the replication origin and rep genes from pOR1 and the cfxA gene from Bacteroides vulgatus, which codes for resistance to the antibiotic cefoxitin, into plasmid pGEM7 by using E. coli as a host. pOREC1 was electroporated into O. rhinotracheale and yielded cefoxitin-resistant transformants. The pOREC1 isolated from these transformants was reintroduced into E. coli, demonstrating that pOREC1 acts as an independent replicon in both E. coli and O. rhinotracheale, fulfilling the criteria for a shuttle plasmid that can be used for transformation, targeted mutagenesis, and the construction of defined attenuated vaccine strains. PMID:15466524

  13. Expression, purification and preliminary X-ray analysis of the Neisseria meningitidis outer membrane protein PorB

    SciTech Connect

    Tanabe, Mikio; Iverson, Tina M.

    2010-01-28

    The Neisseria meningitidis outer membrane protein PorB was expressed in Escherichia coli and purified from inclusion bodies by denaturation in urea followed by refolding in buffered LDAO on a size-exclusion column. PorB has been crystallized in three different crystal forms: C222, R32 and P6{sub 3}. The C222 crystal form may contain either one or two PorB monomers in the asymmetric unit, while both the R32 and P6{sub 3} crystal forms contained one PorB monomer in the asymmetric unit. Of the three, the P6{sub 3} crystal form had the best diffraction quality, yielding data extending to 2.3 {angstrom} resolution.

  14. Application of POR-Tveks to the radiochemical recovery of yttrium-90

    SciTech Connect

    Maksimova, A.M.; Kvasnitskii, I.B.

    1988-01-01

    The authors describe a method for the radiochemical analysis of fish bones for the accumulation of strontium 90 and yttrium 90 from power plant contamination of surface waters which involves labelling the sample with isotopes and subsequent adsorption of the yttrium component with the use of POR-Tveks, an adsorbent based on a copolymer of styrene and divinylbenzene with heteroradical phosphine oxide. The yield of yttrium is determined from the mass of the oxide and from the half-life of the yttrium isotope.

  15. Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.

    PubMed

    Kawa, Diane E; Stephens, Richard S

    2002-05-15

    The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines. PMID:11994474

  16. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. PMID:27285815

  17. Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

    PubMed Central

    González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

    2011-01-01

    Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

  18. Effect of SPM-based cleaning POR on EUV mask performance

    NASA Astrophysics Data System (ADS)

    Choi, Jaehyuck; Lee, Han-shin; Yoon, Jinsang; Shimomura, Takeya; Friz, Alex; Montgomery, Cecilia; Ma, Andy; Goodwin, Frank; Kang, Daehyuk; Chung, Paul; Shin, Inkyun; Cho, H.

    2011-11-01

    EUV masks include many different layers of various materials rarely used in optical masks, and each layer of material has a particular role in enhancing the performance of EUV lithography. Therefore, it is crucial to understand how the mask quality and patterning performance can change during mask fabrication, EUV exposure, maintenance cleaning, shipping, or storage. The fact that a pellicle is not used to protect the mask surface in EUV lithography suggests that EUV masks may have to undergo more cleaning cycles during their lifetime. More frequent cleaning, combined with the adoption of new materials for EUV masks, necessitates that mask manufacturers closely examine the performance change of EUV masks during cleaning process. We have investigated EUV mask quality and patterning performance during 30 cycles of Samsung's EUV mask SPM-based cleaning and 20 cycles of SEMATECH ADT exposure. We have observed that the quality and patterning performance of EUV masks does not significantly change during these processes except mask pattern CD change. To resolve this issue, we have developed an acid-free cleaning POR and substantially improved EUV mask film loss compared to the SPM-based cleaning POR.

  19. Methodology for obtaining stakeholder assessments of obesity policy options in the PorGrow project.

    PubMed

    Stirling, A; Lobstein, T; Millstone, E

    2007-05-01

    The Policy Options for Responding to the Growing Challenge of Obesity Research Project (PorGrow) study provided a unique opportunity to develop a large-scale application of a semi-quantitative technique for exploring interviewees' views on options to tackle obesity, using multi-criteria mapping. This 'heuristic' approach utilizes the advantages of a structured interviews framework by predefining a set of options for appraisal, while leaving interviewees free to select their own criteria for making their judgements. Additional information can be gleaned from the interview transcripts and related materials to set the appraisals in their policy context, and allowing interviewees to express their views on the options presented and their own appraisals. The PorGrow study team agreed a predefined set of 20 options for appraisal, and interviewed sets of stakeholders representing more than 20 aspects of policy development in each of the nine participating countries. The details of the methodology adopted are set out in this paper. PMID:17371304

  20. Effects of heme precursors on CYP1A2 and POR expression in the baculovirus/Spodoptera frugiperda system☆

    PubMed Central

    Lu, Huiyuan; Ma, Jun; Liu, Nian; Wang, Shoulin

    2010-01-01

    Objective CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to investigate the effects of heme precursors on the expression of CYP1A2 and POR. Methods The heme precursors [δ-Aminolaevulinic Acid (5-ALA), Fe3+ and hemin] were introduced into the system to evaluate their effects on the expression of CYP1A2, POR and their co-expression. All the proteins were identified using immunoblotting, CO-difference spectroscopy, or cytochrome c assay. Results In the present study, functional CYP1A2 and POR were successfully expressed in the baculovirus/sf9 system, and both of them showed high activities. Co-addition of 5-ALA and Fe3+ significantly improved expression of CYP1A2 by about 50% compared with the addition of 5-ALA, Fe3+ or hemin alone. Either co-addition of 5-ALA and Fe3+ or addition of 5-ALA or Fe3+ alone improved the POR expression level 2 fold and its activity 7-10 fold compared with control (no addition). However, unlike CYP1A2, there was no difference between the co-addition and addition of these heme precursors alone. Different ratios of BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1 ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression. Surprisingly, the addition of 0.1 mM 5-ALA or Fe3+ alone, but not their co-addition, could significantly improve the CYP1A2 and POR co-expression (P < 0.05). Conclusion 5-ALA and Fe3+ increased the expression of CYP1A2 and POR in a baculovirus/sf9 system, but the pattern of their expression was different between their expression alone and co-expression. PMID:23554636

  1. Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter.

    PubMed

    Higgins, A M; Banik, B L; Brown, J L

    2015-02-01

    Bone grafting procedures in the United States rely heavily upon autografts and allografts, which are donor-dependent, cause donor site pain, and can transmit disease. Synthetic bone grafts can reduce these risks; however, synthetics lack the bone differentiating (osteoinductive) abilities of auto- and allografts. Achieving innate osteoinductive properties of synthetics through surface modifications is currently under investigation. This study focuses on nanofibers, with emphasis on how fiber diameter and the potential curvature sensor POR1 affect the activation of the signaling molecules Rac1 and Arf1, and leading to expression of alkaline phosphatase (ALP), an osteoinductive marker. Diameters of 0.1, 0.3, and 1.0 μm were compared against a flat control. The highest level of Rac1 activation was achieved on the smallest fibers (0.1 μm), a trend that was lost in POR1 knockdowns. This supports the hypothesis that on small nanofibers, POR1 favorably binds to highly curved cell membranes, which allows Rac1 to subsequently dissociate and activate. When the curvature is insufficient to bind POR1, POR1 binds to inactive Rac1 and competitively inhibits its activation. Arf1 activation followed an opposite trend, with the largest nanofibers exhibiting the highest activity. This trend reinforces the known interaction between Rac1 and Arf1 through the GIT-PIX complex, an Arf1 GAP and Rac1 GEF, respectively. Large, (1.0 μm), nanofibers demonstrated the highest ALP activity, indicating that ALP expression is inversely dependent on Rac1 activation. Knockdown of POR1 resulted in increased ALP activity across the substrates but without regard to the curvature sensing trend seen previously. Thus, POR1 senses curvature and increases Rac1 activity, which negatively regulates bone differentiation. PMID:25539497

  2. Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase (POR)

    PubMed Central

    Agrawal, Vishal; Choi, Ji Ha; Giacomini, Kathleen M.; Miller, Walter L.

    2010-01-01

    Objectives CYP3A4 receives electrons from P450 oxidoreductase (POR) to metabolize about 50% of clinically used drugs. There is substantial inter-individual variation in CYP3A4 catalytic activity that is not explained by CYP3A4 genetic variants. CYP3A4 is flexible and distensible, permitting it to accommodate substrates varying in shape and size. To elucidate mechanisms of variability in CYP3A4 catalysis, we examined the effects of genetic variants of POR, and explored the possibility that substrate-induced conformational changes in CYP3A4 differentially affect the ability of POR variants to support catalysis. Methods We expressed human CYP3A4 and four POR variants (Q153R, A287P, R457H, A503V) in bacteria, reconstituted them in vitro and measured the Michaelis constant and maximum velocity with testosterone, midazolam, quinidine and erythromycin as substrates. Results POR A287P and R457H had low activity with all substrates; Q153R had 76–94% of wild type (WT) activity with midazolam and erythromycin, but 129–150% activity with testosterone and quinidine. The A503V polymorphism reduced CYP3A4 activity to 61–77% of wild type with testosterone and midazolam, but had nearly wild type activity with quinidine and erythromycin. Conclusion POR variants affect CYP3A4 activities. The impact of a POR variant on catalysis by CYP3A4 is substrate-specific, probably due to substrate-induced conformational changes in CYP3A4. PMID:20697309

  3. Intermitência alfvênica gerada por caos na atmosfera solar e no vento solar

    NASA Astrophysics Data System (ADS)

    Rempel, E. L.; Chian, A. C.-L.; Macau, E. E. N.; Rosa, R. R.

    2003-08-01

    Dados medidos no vento solar rápido proveniente dos buracos coronais revelam que os plasmas no meio interplanetário são dominados por flutuações Alfvênicas, caracterizadas por uma alta correlação entre as variações do campo magnético e da velocidade do plasma. As flutuações exibem muitas características esperadas em turbulência magneto-hidrodinâmica totalmente desenvolvida, tais como intermitência e espectros contínuos. Contudo, os mecanismos responsáveis pela evolução de turbulência Alfvênica intermitente não são completamente compreendidos. Neste trabalho a teoria de caos é usada para explicar como sistemas Alfvênicos, modelados pela equação Schrödinger não-linear derivativa e pela equação Kuramoto-Sivashinsky, podem se tornar fortemente caóticos à medida em que parâmetros do plasma são variados. Pequenas perturbações no parâmetro de dissipação podem fazer com que o sistema mude bruscamente de um regime periódico, ou fracamente caótico, para um regime fortemente caótico. As séries temporais das flutuações do campo magnético nos regimes fortemente caóticos exibem comportamento intermitente, em que fases laminares ou fracamente caóticas são interrompidas por fortes estouros caóticos. É mostrado que o regime fortemente caótico é atingido quando as soluções periódicas ou fracamente caóticas globalmente estáveis interagem com soluções do sistema que são fortemente caóticas, mas globalmente instáveis. Estas soluções globalmente instáveis são conjuntos caóticos não-atrativos conhecidos como selas caóticas, e são responsáveis pelos fortes estouros nos regimes intermitentes. Selas caóticas têm sido detectadas experimentalmente em uma grande variedade de sistemas, sendo provável que elas desempenhem um papel importante na turbulência intermitente observada em plasmas espaciais.

  4. National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study▿

    PubMed Central

    Critchley, Ian A.; Brown, Steven D.; Traczewski, Maria M.; Tillotson, Glenn S.; Janjic, Nebojsa

    2007-01-01

    Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to β-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. β-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 μg/ml for S. pneumoniae, 1 μg/ml for H. influenzae, and 0.5 μg/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused

  5. National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005-2006 U.S. Faropenem surveillance study.

    PubMed

    Critchley, Ian A; Brown, Steven D; Traczewski, Maria M; Tillotson, Glenn S; Janjic, Nebojsa

    2007-12-01

    Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections

  6. Comparative in vitro assessment of sparfloxacin activity and spectrum using results from over 14,000 pathogens isolated at 190 medical centers in the USA. SPAR Study Group.

    PubMed

    Ballow, C H; Jones, R N; Johnson, D M; Deinhart, J A; Schentag, J J

    1997-11-01

    Sparfloxacin, a new orally administered fluoroquinolone, was tested against 14,182 clinical strains isolated (generally blood stream and respiratory tract cultures) at nearly 200 hospitals in the United States (USA) and Canada. Sparfloxacin activity was compared with 13 other compounds by Etest (AB BIODISK, Solna, Sweden), broth microdilution, or a standardized disk diffusion method. Using the Food and Drug Administration/product package insert MIC breakpoint for sparfloxacin susceptibility (< or = 0.5 microgram/ml), 94% of Streptococcus pneumoniae (2666 isolates) and 89% of the other streptococci (554 isolates) were susceptible. However, at < or = 1 microgram/ml (the breakpoint for all nonstreptococcal species) sparfloxacin susceptibility rates increased to 100% and 98%, respectively, for the two groups of streptococci. Only 50% and 65% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/ml) and penicillin (MIC90, 1.5 micrograms/ml), respectively. Although there were significant differences between regions in the USA in the frequency of penicillin-resistant pneumococcal strains, results indicate that the overall sparfloxacin MIC90 was uniformly at 0.5 microgram/ml. Nearly all (> or = 99%) Haemophilus species and Moraxella catarrhalis, including those harboring beta-lactamases, were susceptible to sparfloxacin, ciprofloxacin, and amoxicillin/clavulanic acid. Only cefprozil and macrolides demonstrated lower potency and spectrum against these two species. Sparfloxacin was active against oxacillin-susceptible Staphylococcus aureus (96 to 97%), Klebsiella spp. (95%), and other tested enteric bacilli (93%). Comparison between broth microdilution MIC and disk diffusion interpretive results for M. catarrhalis, Staphylococcus aureus, and the Enterobacteriaceae showed an absolute intermethod categorical agreement of > 95% using current sparfloxacin breakpoints, in contrast to those of cefpodoxime for S. aureus where a conspicuous discord (98% versus 59

  7. Fabrication of por-Si/SnO{sub x} nanocomposite layers for gas microsensors and nanosensors

    SciTech Connect

    Bolotov, V. V. Korusenko, P. M.; Nesov, S. N.; Povoroznyuk, S. N.; Roslikov, V. E.; Kurdyukova, E. A.; Sten'kin, Yu. A.; Shelyagin, R. V.; Knyazev, E. V.; Kan, V. E.; Ponomareva, I. V.

    2011-05-15

    Two-phase nanocomposite layers based on porous silicon and nonstoichiometric tin oxide were fabricated by various methods. The structure, as well as elemental and phase composition, of the obtained nanocomposites were studied using transmission and scanning electron microscopy, Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy. The results obtained confirm the formation of nanocomposite layers with a thickness as large as 2 {mu}m thick and SnO{sub x} stoichiometry coefficients x = 1.0-2.0. Significant tin diffusion into the porous silicon matrix with D{sub eff} Almost-Equal-To 10{sup -14} cm{sup 2} s{sup -1} was observed upon annealing at 770 K. Test sensor structures based on por-Si/SnO{sub x} nanocomposite layers grown by magnetron deposition showed fairly high stability of properties and sensitivity to NO{sub 2}.

  8. Recovery of naphthalene during evaporative concentration. [Tenax; XAD-2; POR-Q, XE-340

    SciTech Connect

    Higgins, C.E.; Guerin, M.R.

    1980-10-01

    The analysis of trace organics usually requires concentrating organic extracts to small volumes prior to instrumental analysis. The use of a concentration apparatus employing a nitrogen blanket and reduced pressure is desirable because the inert atmosphere and low temperature help to ensure stable composition. Unfortunately, diaromatic compounds such as the naphthalenes and biphenyls are frequently almost completely lost during the concentration step. Even under carefully controlled conditions only 26 +- 11% of the naphthalene is recovered. By placing a sorbent either in or downstream of the evaporation concentration flask, recovery of diaromatic compounds can be improved significantly. In this investigation, the following sorbents, Tenax, XAD-2, POR-Q, and XE-340 were tested. Recoveries with and without the use of sorbents, effects of solute concentration, purge time after solvent removal, and type of solvent used are reported here.

  9. Using the PORS Problems to Examine Evolutionary Optimization of Multiscale Systems

    SciTech Connect

    Reinhart, Zachary; Molian, Vaelan; Bryden, Kenneth

    2013-01-01

    Nearly all systems of practical interest are composed of parts assembled across multiple scales. For example, an agrodynamic system is composed of flora and fauna on one scale; soil types, slope, and water runoff on another scale; and management practice and yield on another scale. Or consider an advanced coal-fired power plant: combustion and pollutant formation occurs on one scale, the plant components on another scale, and the overall performance of the power system is measured on another. In spite of this, there are few practical tools for the optimization of multiscale systems. This paper examines multiscale optimization of systems composed of discrete elements using the plus-one-recall-store (PORS) problem as a test case or study problem for multiscale systems. From this study, it is found that by recognizing the constraints and patterns present in discrete multiscale systems, the solution time can be significantly reduced and much more complex problems can be optimized.

  10. Display of a PorA peptide from Neisseria meningitidis on the bacteriophage T4 capsid surface.

    PubMed Central

    Jiang, J; Abu-Shilbayeh, L; Rao, V B

    1997-01-01

    The exterior of bacteriophage T4 capsid is coated with two outer capsid proteins, Hoc (highly antigenic outer capsid protein; molecular mass, 40 kDa) and Soc (small outer capsid protein; molecular mass, 9 kDa), at symmetrical positions on the icosahedron (160 copies of Hoc and 960 copies of Soc per capsid particle). Both these proteins are nonessential for phage infectivity and viability and assemble onto the capsid surface after completion of capsid assembly. We developed a phage display system which allowed in-frame fusions of foreign DNA at a unique cloning site in the 5' end of hoc or soc. A DNA fragment corresponding to the 36-amino-acid PorA peptide from Neisseria meningitidis was cloned into the display vectors to generate fusions at the N terminus of Hoc or Soc. The PorA-Hoc and PorA-Soc fusion proteins retained the ability to bind to the capsid surface, and the bound peptide was displayed in an accessible form as shown by its reactivity with specific monoclonal antibodies in an enzyme-linked immunosorbent assay. By employing T4 genetic strategies, we show that more than one subtype-specific PorA peptide can be displayed on the capsid surface and that the peptide can also be displayed on a DNA-free empty capsid. Both the PorA-Hoc and PorA-Soc recombinant phages are highly immunogenic in mice and elicit strong antipeptide antibody titers even with a weak adjuvant such as Alhydrogel or no adjuvant at all. The data suggest that the phage T4 hoc-soc system is an attractive system for display of peptides on an icosahedral capsid surface and may emerge as a powerful system for construction of the next generation multicomponent vaccines. PMID:9353063

  11. Rescue of cytochrome P450 oxidoreductase (Por) mouse mutants reveals functions in vasculogenesis, brain and limb patterning linked to retinoic acid homeostasis.

    PubMed

    Ribes, Vanessa; Otto, Diana M E; Dickmann, Leslie; Schmidt, Katy; Schuhbaur, Brigitte; Henderson, Colin; Blomhoff, Rune; Wolf, C Roland; Tickle, Cheryll; Dollé, Pascal

    2007-03-01

    Cytochrome P450 oxidoreductase (POR) acts as an electron donor for all cytochrome P450 enzymes. Knockout mouse Por(-/-) mutants, which are early embryonic (E9.5) lethal, have been found to have overall elevated retinoic acid (RA) levels, leading to the idea that POR early developmental function is mainly linked to the activity of the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol. 23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene, we show that Por(-/-) embryos exhibit both elevated and ectopic RA signaling activity e.g. in cephalic and caudal tissues. Two strategies were used to functionally demonstrate that decreasing retinoid levels can reverse Por(-/-) phenotypic defects, (i) by culturing Por(-/-) embryos in defined serum-free medium, and (ii) by generating compound mutants defective in RA synthesis due to haploinsufficiency of the retinaldehyde dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the Por(-/-) early phenotype, the latter allowing mutants to be recovered up until E13.5. Abnormal brain patterning, with posteriorization of hindbrain cell fates and defective mid- and forebrain development and vascular defects were rescued in E9.5 Por(-/-) embryos. E13.5 Por(-/-); Raldh2(+/-) embryos exhibited abdominal/caudal and limb defects that strikingly phenocopy those of Cyp26a1(-/-) and Cyp26b1(-/-) mutants, respectively. Por(-/-); Raldh2(+/-) limb buds were truncated and proximalized and the anterior-posterior patterning system was not established. Thus, POR function is indispensable for the proper regulation of RA levels and tissue distribution not only during early embryonic development but also in later morphogenesis and molecular patterning of the brain, abdominal/caudal region and limbs. PMID:17126317

  12. Global Microlending in Education Reform: Enseñá Por Argentina and the Neoliberalization of the Grassroots

    ERIC Educational Resources Information Center

    Friedrich, Daniel S.

    2010-01-01

    This article examines the workings and underlying assumptions behind Enseñá por Argentina (Teach for Argentina), one specific program that takes part in the larger and expanding network of Teach for All, by thinking about the ways in which a global push for redefining teaching and teacher education encounters local characteristics and histories,…

  13. [Professor Frantisek Por MD and Professor Robert Klopstock MD, students at Budapest and Prague Faculties of Medicine].

    PubMed

    Mydlík, M; Derzsiová, K

    2010-11-01

    Professor Frantisek Por MD and Professor Robert Klopstock MD were contemporaries, both born in 1899, one in Zvolen, the other in Dombovar, at the time of Austro-Hungarian Monarchy. Prof. Por attended the Faculty of Medicine in Budapest from 1918 to 1920, and Prof. Klopstock studied at the same place between 1917 and 1919. From 1920 until graduation on 6th February 1926, Prof. Por continued his studies at the German Faculty of Medicine, Charles University in Prague. Prof. Klopstock had to interrupt his studies in Budapest due to pulmonary tuberculosis; he received treatment at Tatranske Matliare where he befriended Franz Kafka. Later, upon Kafka's encouragement, he changed institutions and continued his studies at the German Faculty of Medicine, Charles University in Prague, where he graduated the first great go. It is very likely that, during their studies in Budapest and Prague, both professors met repeatedly, even though their life paths later separated. Following his graduation, Prof. Por practiced as an internist in Prague, later in Slovakia, and from 1945 in Kosice. In 1961, he was awarded the title of university professor of internal medicine at the Faculty of Medicine, Pavol Jozef Safarik University in Kosice, where he practiced until his death in 1980. Prof. Klopstock continued his studies in Kiel and Berlin. After his graduation in 1933, he practiced in Berlin as a surgeon and in 1938 left for USA. In 1962, he was awarded the title of university professor of pulmonary surgery in NewYork, where he died in 1972. PMID:21250499

  14. Functional POR A503V is associated with the risk of bladder cancer in a Chinese population

    PubMed Central

    Xiao, Xue; Ma, Gaoxiang; Li, Shushu; Wang, Meilin; Liu, Nian; Ma, Lan; Zhang, Zhan; Chu, Haiyan; Zhang, Zhengdong; Wang, Shou-Lin

    2015-01-01

    Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls, and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57–0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%), and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity, and should be a potential biomarker for predicting the susceptibility to human bladder cancer. PMID:26123203

  15. Inversor Resonante de Tres Elementos L-LC con Caracteristica Cortocircuitable para Aplicaciones de Calentamiento por Induccion

    NASA Astrophysics Data System (ADS)

    Espi Huerta, Jose Miguel

    Los generadores de calentamiento por induccion son puentes inversores con carga resonante, cuya mision es basicamente crear una corriente sinusoidal de gran amplitud sobre la "bobina de caldeo", que forma parte del tanque resonante. En el interior de esta bobina se introduce la pieza que se desea calentar. EI campo magnetico creado induce corrientes superficiales (corrientes de Foucault) sobre la pieza, que producen su calentamiento. Los tanques resonantes (tambien llamados osciladores) utilizados en la actualidad son el resonante serie y el resonante paralelo. Aunque ya desde hace algun tiempo se vienen construyendo generadores de alta potencia basados en estos dos osciladores, el exito nunca ha. sido completo en ninguno de los dos casos. Tal y como se explica en la introduccion de esta memoria, los puentes inversores utilizados deben operar sobre una carga inductiva (corriente retrasada) para evitar el fenomeno de la recuperacion inversa de sus diodos y la consiguiente ruptura de los transistores. De la restriccion topologica anterior se deduce que el generador paralelo debe conmutar a frecuencias inferiores a la resonancia, y el serie a frecuencias superiores. A esta restriccion topologica hay que unir otra que es exclusiva del calentamiento por induccion: La corriente por la bobina de caldeo debe ser sinusoidal. De no ser asi, resultaria imposible disponer toda la potencia de calentamiento sobre la pieza en el espesor requerido por la aplicacion. Como consecuencia, los inversores no pueden operar por debajo de la frecuencia de resonancia del oscilador, pues en ese caso se amplifican los armonicos de orden superior de la tension/corriente de entrada situados sobre la resonancia, con la consiguiente distorsion de la corriente de salida. La conjuncion de las dos restricciones anteriores obligan al inversor paralelo a funcionar a la frecuencia de resonancia del oscilador. Esto imposibilita un control por variacion de frecuencia, regulandose la potencia desde la

  16. Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review

    PubMed Central

    Sethi, Sanjay; Murphy, Timothy F.

    2001-01-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. The precise role of bacterial infection in the course and pathogenesis of COPD has been a source of controversy for decades. Chronic bacterial colonization of the lower airways contributes to airway inflammation; more research is needed to test the hypothesis that this bacterial colonization accelerates the progressive decline in lung function seen in COPD (the vicious circle hypothesis). The course of COPD is characterized by intermittent exacerbations of the disease. Studies of samples obtained by bronchoscopy with the protected specimen brush, analysis of the human immune response with appropriate immunoassays, and antibiotic trials reveal that approximately half of exacerbations are caused by bacteria. Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most common causes of exacerbations, while Chlamydia pneumoniae causes a small proportion. The role of Haemophilus parainfluenzae and gram-negative bacilli remains to be established. Recent progress in studies of the molecular mechanisms of pathogenesis of infection in the human respiratory tract and in vaccine development guided by such studies promises to lead to novel ways to treat and prevent bacterial infections in COPD. PMID:11292642

  17. The role of temafloxacin in the community setting: an overview.

    PubMed

    Ball, P

    1991-12-01

    The use of new quinolones has become established therapy for many community infections including urinary tract infection, genital infection, soft tissue infection and some forms of lower respiratory tract infection. However, there has been an undercurrent of anxiety concerning their efficacy in pneumococcal infections. Temafloxacin has improved activity against pneumococci and its high oral bioavailability and excellent penetration into respiratory tissues now combine to provide a suitable profile for the management of a wider range of respiratory infections. Eradication rates in acute exacerbations of chronic bronchitis collated from individual studies are 98% overall and 100% in pneumococcal infections. Furthermore, eradication rates in smokers and the elderly illustrate significant advantages for temafloxacin when compared with previous quinolones. In pneumonia, a twice-daily temafloxacin regimen has given equivalent overall results to those of amoxycillin (84.6% vs 80%). In proven pneumococcal pneumonia, equivalent results (78.6% vs 78.4%) have been obtained with both drugs. A daily 600 mg dose of temafloxacin eradicated 94% of pneumococcal isolates in one study and in another this agent given twice-daily orally proved comparable to parenteral cephalosporin treatment. Temafloxacin shares with other quinolones excellent bacteriological and clinical efficacy against Haemophilus influenzae and Moraxella catarrhalis. These results and the lack of potential interaction with theophylline indicate temafloxacin to be suitable for domiciliary management of respiratory tract infections in addition to a broad range of other community infectious diseases. PMID:1664825

  18. [Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis].

    PubMed

    Niederman, M S

    1999-01-01

    Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction. PMID:10436551

  19. Gemifloxacin.

    PubMed

    Lowe, M N; Lamb, H M

    2000-05-01

    Gemifloxacin is a fluoroquinolone antibacterial agent which has an enhanced affinity for topoisomerase i.v.. It has potent activity against most Gram-positive bacteria, particularly Streptococcus pneumoniae. Gemifloxacin is over 30-fold more active than ciprofloxacin and 4- to 8-fold more active than moxifloxacin against this pathogen. Gemifloxacin has excellent activity against Haemophilus influenzae and Moraxella catarrhalis, and is unaffected by beta-lactamase production. It is generally 2-fold less active than ciprofloxacin against most Enterobacteriaceae. Atypical respiratory pathogens (Legionella, Mycoplasma and Chlamydia spp.) are highly susceptible to gemifloxacin. Preliminary results from phase II trials show that oral gemifloxacin 320 mg/day produced bacteriological responses of 94.7% in patients with acute exacerbations of chronic bronchitis and 95% of patients with uncomplicated urinary tract infections. Adverse events included nausea, abdominal pain, headache and mild rash in patients and healthy volunteers treated with gemifloxacin 320 mg/day. Gemifloxacin has a low potential for mild phototoxicity (comparable to that of ciprofloxacin). PMID:10852645

  20. Microbiology of chronic rhinosinusitis.

    PubMed

    Brook, I

    2016-07-01

    Most sinus infections are viral and only a small percentage develop bacterial infection. Rhino-, influenza, and para-influenza viruses are the most frequent viral causes of sinusitis. The most common bacterial isolates from children and adult patients with community-acquired acute bacterial sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic organisms (Prevotella and Porphyromonas, Fusobacterium, and Peptostreptococcus spp.) are the commonest isolates in chronic rhinosinusitis (CRS). Aerobic and anaerobic beta lactamase-producing bacteria (BLPB) were recovered from over a third of these patients. Methicillin-resistant S. aureus (MRSA) accounted for over 60 % of S. aureus isolates. Pseudomonas aeruginosa and other aerobic and facultative Gram-negative rods are frequently recovered in nosocomial sinusitis, the immunocompromised host, individuals with human immunodeficiency virus infection, and in cystic fibrosis. The CRS infection evolves the formation of a biofilm that might play a significant role in the pathogenesis and persistence of CRS. The microbiology of sinusitis is influenced by previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens. Recognition of the unique microbiology of CRS and their antimicrobial susceptibility is of great importance when selecting antimicrobial therapy. PMID:27086363

  1. Detection of respiratory pathogens in pediatric acute otitis media by PCR and comparison of findings in the middle ear and nasopharynx.

    PubMed

    Yatsyshina, Svetlana; Mayanskiy, Nikolay; Shipulina, Olga; Kulichenko, Tatiana; Alyabieva, Natalia; Katosova, Lyubovj; Lazareva, Anna; Skachkova, Tatyana; Elkina, Maria; Matosova, Svetlana; Shipulin, German

    2016-05-01

    We conducted a series of polymerase chain reactions (PCRs) in order to detect bacteria (7 species) and viruses (17 species) in middle ear fluid (MEF) and nasopharynx (Nph) of children with acute otitis media (AOM; n=179). Bacterial and viral nucleic acids were detected in MEF of 78.8% and 14.5% patients, respectively. The prevalence was as follows: Streptococcus pneumoniae, 70.4%; Haemophilus influenzae, 17.9%; Staphylococcus aureus, 16.8%; Streptococcus pyogenes, 12.3%; Moraxella catarrhalis, 9.5%; rhinovirus, 9.5%; and adenovirus, 3.4%. The overall rate of PCR-positive specimens for bacterial pathogens was 2.6 times higher, compared to culture results. The rate of PCR-positive results and the distribution of pathogens in the Nph were similar to those in the MEF. Nph PCR results had variable positive predictive values and high negative predictive values in predicting MEF findings. Our results indicate that Nph PCR could be a practical tool for examining respiratory pathogens in children with acute infections. PMID:26971180

  2. Prediction of piperacillin-tazobactam susceptibility among Enterobacteriaceae, Pseudomonas aeruginosa, and other bacteria using ticarcillin-clavulanic acid, ceftazidime, and other broad-spectrum antimicrobial in vitro test results.

    PubMed

    Jones, R N; Sutton, L D; Cantrell, H F; Lankford, R B

    1994-11-01

    The ability of various in vitro beta-lactam susceptibility test results to predict the susceptibility of piperacillin-tazobactam (a new beta-lactam-beta-lactamase inhibitor combination) was assessed using more than 46,000 recent clinical isolates. The organisms were tested by reference-quality National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution procedures and interpreted by the currently published NCCLS criteria. The recommended antimicrobial tests that would accurately predict the piperacillin-tazobactam in vitro efficacy had an overall very major, false-susceptible rate of only 0.6% (< or = 1.5% is acceptable). The following drug tests can be used to judge piperacillin-tazobactam activity and spectrum (low patient risk) conservatively: for Enterobacteriaceae use ticarcillin-clavulanic acid results (0.6% very major error); for Pseudomonas aeruginosa use piperacillin (0.1%) results; for enterococci use ampicillin or ampicillin-sulbactam (1.8%) results; for Haemophilus influenzae and Moraxella catarrhalis use cefotaxime or cefuroxime or ceftriaxone (1.5%); and for staphylococci use oxacillin by NCCLS recommendations. When the piperacillin-tazobactam testing reagents become available, the direct testing of this combination should be applied to relevant clinical isolates. The piperacillin-tazobactam break points should be reassessed as indicated by the cited minimum inhibitory concentration population analysis to improve predictive accuracy; H. influenzae susceptibility modified to < or = 2/4 micrograms/ml and Enterococcus species susceptibility tested at < or = 16/4 micrograms. PMID:7874881

  3. Moxifloxacin in the management of exacerbations of chronic bronchitis and COPD

    PubMed Central

    Miravitlles, Marc

    2007-01-01

    Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400 mg once daily. Among the fluoroquinolones, the ratio of the area under the concentration-time curve (AUC) to minimal inhibitory concentration of moxifloxacin is the highest against S. pneumoniae. Moxifloxacin has demonstrated better eradication in exacerbations of CB and COPD compared with standard therapy, in particular, with macrolides. Patients treated with moxifloxacin showed a prolonged time to the next exacerbation and observational studies suggest that moxifloxacin induces a faster release of symptoms of exacerbation. Some guidelines recommend the use of moxifloxacin as first-line therapy in bacterial exacerbations in patients with moderate to severe COPD and in patients with mild COPD with risk factors. The current article reviews the use of moxifloxacin in bacterial exacerbations of CB and COPD. PMID:18229559

  4. Otopathogens Detected in Middle Ear Fluid Obtained during Tympanostomy Tube Insertion: Contrasting Purulent and Non-Purulent Effusions

    PubMed Central

    Holder, Robert C.; Kirse, Daniel J.; Evans, Adele K.; Whigham, Amy S.; Peters, Timothy R.; Poehling, Katherine A.; Swords, William E.; Reid, Sean D.

    2015-01-01

    Otitis media is a prominent disease among children. Previous literature indicates that otitis media is a polymicrobial disease, with Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis and Moraxella catarrhalis being the most commonly associated bacterial pathogens. Recent literature suggests that introduction of pneumococcal conjugate vaccines has had an effect on the etiology of otitis media. Using a multiplex PCR procedure, we sought to investigate the presence of the aforementioned bacterial pathogens in middle ear fluid collected from children undergoing routine tympanostomy tube placement at Wake Forest Baptist Medical Center during the period between January 2011 and March 2014. In purulent effusions, one or more bacterial organisms were detected in ~90% of samples. Most often the presence of H. influenzae alone was detected in purulent effusions (32%; 10 of 31). In non-purulent effusions, the most prevalent organism detected was A. otitidis (26%; 63 of 245). Half of the non-purulent effusions had none of these otopathogens detected. In purulent and non-purulent effusions, the overall presence of S. pneumoniae was lower (19%; 6 of 31, and 4%; 9 of 245, respectively) than that of the other pathogens being identified. The ratio of the percentage of each otopathogen identified in purulent vs. non-purulent effusions was >1 for the classic otopathogens but not for A. otitidis. PMID:26039250

  5. Otitis media in a population of black American and white American infants, 0-2 years of age.

    PubMed

    Casselbrant, M L; Mandel, E M; Kurs-Lasky, M; Rockette, H E; Bluestone, C D

    1995-08-01

    To determine the incidence of otitis media (OM) and the bacteriology of acute otitis media (AOM) in a clinic population of young children in Pittsburgh, 138 black infants and 60 white infants were followed from birth to 2 years of age, examined at monthly intervals and whenever an upper respiratory tract infection (URI) or OM intervened. By 24 months of age the cumulative incidence of episodes of AOM was 43% and 42%, and of episodes of middle-ear effusion (MEE) was 86% and 85% in black and white infants, respectively. The average rate of episodes of AOM was 0.41 and 0.39 and of episodes of MEE was 1.68 and 1.70 in black and white infants, respectively. Tympanocentesis was performed for episodes of AOM and the following organisms were isolated from black and white infants, respectively: Streptococcus pneumoniae 43% and 43% of episodes; Moraxella catarrhalis 24% and 24%; non-typable Haemophilus influenzae 18% and 24%; and Haemophilus influenzae type b 5% and 0%. In both black and white infants first born children had less ear disease. We found no difference in the incidence of otitis media during the first 2 years of life between black and white infants. PMID:7558637

  6. Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens.

    PubMed

    James, N C; Donn, K H; Collins, J J; Davis, I M; Lloyd, T L; Hart, R W; Powell, J R

    1991-09-01

    The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly Branhamella) catarrhalis were significantly greater (P less than 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxime compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime. PMID:1952858

  7. The pharmacokinetics, tissue penetration and in-vitro activity of loracarbef, a beta-lactam antibiotic of the carbacephem class.

    PubMed

    Lees, A S; Andrews, J M; Wise, R

    1993-12-01

    The pharmacokinetics of loracarbef in plasma and a mild inflammatory exudate were studied in human volunteers. After a single oral dose of 400 mg, a mean maximum drug concentration (Cmax) of 17.8 mg/L was achieved in the plasma at 1.2 h (mean Tmax). The mean plasma elimination half-life (T1/2) was 1.3 h. In the inflammatory exudate the mean Cmax was 8.9 mg/L at a mean Tmax of 2.0 h and with a mean T1/2 of 1.7 h. The mean penetration into the inflammatory exudate was 90.1%. The in-vitro activity of loracarbef was determined against Haemophilus influenzae and Moraxella catarrhalis (MIC90s of 4 mg/L and 1 mg/L respectively, regardless of beta-lactamase production), as well as Streptococcus pneumoniae (MIC90 of 2 mg/L). Loracarbef was also active against Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae (MIC90s of < or = 2 mg/L). The in-vitro activity and pharmacokinetics of loracarbef suggest that it would be efficative therapy for patients with community-acquired respiratory and urinary tract infections caused by the most frequently-encountered bacterial pathogens. PMID:8144425

  8. Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions.

    PubMed

    Iauk, Liliana; Acquaviva, Rosaria; Mastrojeni, Silvana; Amodeo, Andrea; Pugliese, Michela; Ragusa, Monica; Loizzo, Monica R; Menichini, Francesco; Tundis, Rosa

    2015-06-01

    The aim of this study was to examine the bioactivity of the methanol fraction (MF) and n-hexane fraction (HF) of Thymus capitatus leaves in relation to their constituents analysed by gas chromatography and gas chromatography-mass spectrometry. The effects of T. capitatus on the growth of pathogenic bacteria associated with respiratory diseases (13 gram-positive and 4 gram-negative) were determined using a microdilution method. The MF was particularly effective on Streptococcus pneumoniae and Moraxella catarrhalis. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing antioxidant power and β-carotene bleaching assays. A strong activity using β-carotene bleaching test was observed with the MF (IC50 of 0.7 μg/mL after 30 min of incubation). In the hypoglycaemic test, a selective α-amylase inhibitory activity was detected with the HF begging the most active (IC50 of 422.5 μg/mL). T. capitatus may represent a source of natural bioactive compounds. PMID:25032744

  9. Antibacterial activity of carbapenems against clinical isolates of respiratory bacterial pathogens in the northeastern region of Japan in 2007.

    PubMed

    Gomi, Kazunori; Fujimura, Shigeru; Fuse, Katsuhiro; Takane, Hidenari; Nakano, Yoshihisa; Kariya, Yasuko; Kikuchi, Toshiaki; Kurokawa, Iku; Tokue, Yutaka; Watanabe, Akira

    2011-04-01

    As the increasing prevalence of resistant strains of respiratory bacterial pathogens has recently been reported, continuous monitoring of the susceptibility of clinical isolates to antibacterial agents is important. We performed a surveillance study focusing on the susceptibility of major respiratory bacterial pathogens in the northeastern region of Japan to carbapenems and control drugs. A total of 168 bacterial strains isolated from patients with respiratory tract infections in 2007 were collected and the minimum inhibitory concentration (MIC) determined. MIC data were subjected to pharmacokinetic/pharmacodynamic analysis with Monte Carlo simulation to calculate the probability of achieving the target of time above MIC with each carbapenem. All Moraxella catarrhalis, Streptococcus pneumoniae, and methicillin-sensitive Staphylococcus aureus isolates were susceptible to carbapenems. Despite the increasing prevalence of β-lactamase-nonproducing ampicillin-resistant strains, all Haemophilus influenzae isolates were susceptible to meropenem. For Pseudomonas aeruginosa, the susceptibility rates for meropenem and biapenem were 76.7%, and the highest probability of achieving pharmacodynamic target (40% of the time above MIC) was obtained with meropenem 0.5 g three times daily as a 4-h infusion (89.4%), followed by meropenem 0.5 g four times daily as a 1-h infusion (88.4%). Carbapenems have retained their position as key drugs for severe respiratory tract infections. PMID:20839026

  10. In Vitro and In Vivo Antibacterial Activities of S-4661, a New Carbapenem

    PubMed Central

    Tsuji, Masakatsu; Ishii, Yoshikazu; Ohno, Akira; Miyazaki, Shuichi; Yamaguchi, Keizo

    1998-01-01

    The in vitro and in vivo antibacterial activities of S-4661, a new 1β-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 μg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 μg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 μg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa. PMID:9449267

  11. Inflammation-associated cytokine analysis identifies presence of respiratory bacterial pathogens in the nasopharynx.

    PubMed

    Pichichero, Michael E; Almudevar, Anthony

    2016-08-01

    We sought to determine if inflammatory cytokines are induced during asymptomatic nasopharyngeal (NP) colonization by the common respiratory bacteria Streptococcus pneumoniae (Spn), non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat). 85 serum samples were studied from 85 children 6-36 months of age when children were healthy and potentially NP colonized with Spn, NTHi or Mcat. Immunoassays were used to quantitate serum sICAM-1, IL-10 and S100A12 levels. Logistic regression was used to develop a predictive model for NP colonization probability for causative bacterial pathogen presence. Serum levels of sICAM-1, IL-10 and S100A12 increased during asymptomatic NP colonization by Spn, NTHi and Mcat. In a statistical model using risk scoring, we found high positive predictive and negative value, sensitivity and specificity when using these three cytokines to identify the presence of Spn, NTHi and Mcat in the NP. For the first time, we show that inflammatory cytokines are induced in serum during asymptomatic NP colonization by Spn, NTHi and Mcat. PMID:27493063

  12. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

    PubMed Central

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-01-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

  13. Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery.

    PubMed

    Bosch, Astrid A T M; Levin, Evgeni; van Houten, Marlies A; Hasrat, Raiza; Kalkman, Gino; Biesbroek, Giske; de Steenhuijsen Piters, Wouter A A; de Groot, Pieter-Kees C M; Pernet, Paula; Keijser, Bart J F; Sanders, Elisabeth A M; Bogaert, Debby

    2016-07-01

    Birth by Caesarian section is associated with short- and long-term respiratory morbidity. We hypothesized that mode of delivery affects the development of the respiratory microbiota, thereby altering its capacity to provide colonization resistance and consecutive pathobiont overgrowth and infections. Therefore, we longitudinally studied the impact of mode of delivery on the nasopharyngeal microbiota development from birth until six months of age in a healthy, unselected birth cohort of 102 children (n=761 samples). Here, we show that the respiratory microbiota develops within one day from a variable mixed bacterial community towards a Streptococcus viridans-predominated profile, regardless of mode of delivery. Within the first week, rapid niche differentiation had occurred; initially with in most infants Staphylococcus aureus predominance, followed by differentiation towards Corynebacterium pseudodiphteriticum/propinquum, Dolosigranulum pigrum, Moraxella catarrhalis/nonliquefaciens, Streptococcus pneumoniae, and/or Haemophilus influenzae dominated communities. Infants born by Caesarian section showed a delay in overall development of respiratory microbiota profiles with specifically reduced colonization with health-associated commensals like Corynebacterium and Dolosigranulum, thereby possibly influencing respiratory health later in life. PMID:27333043

  14. [Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Reported by the Research Group for Testing Imipenem Susceptibility on Clinical Isolates].

    PubMed

    Igari, J

    1990-11-01

    This study was conducted to investigate susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antibacterial agents at 64 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were carried out at each laboratory and the tests were performed according to the disk dilution method recommended by NCCLS in which susceptibilities are classified into "S", "MS", "I" and "R". IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. IPM also had strong activities against Achromobacter xylosoxidans and Pseudomonas aeruginosa, but less active against Flavobacterium spp., E. faecium, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Pseudomonas cepacia. In a study in which activities of IPM against bacteria isolated from different clinical sources were compared, differences in susceptibilities were observed among S. aureus, CNS, A. calcoaceticus and P. aeruginosa, but such differences were not apparent among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens or P. mirabilis. PMID:2287060

  15. [Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Research Group for Testing Imipenem Susceptibility on Clinical Isolates].

    PubMed

    Igari, J

    1990-10-01

    We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at 459 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were performed at each hospital laboratory and the tests were carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: , ++, + and -. IPM had significantly high activity against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Acinetobacter calcoaceticus, Moraxella catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. and should slightly lower activities on coagulase-negative staphylococci (CNS), Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus vulgaris, Providencia stuartii and Pseudomonas aeruginosa than on the above mentioned bacteria. In a comparative study on activities of IPM against bacteria from different clinical sources, no remarkable differences were found due to different sources among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis or A. calcoaceticus, whereas slight differences were found among Staphylococcus aureus, CNS, S. marcescens and P. aeruginosa. PMID:2086814

  16. Ten-Year Study of Acute Otitis Media in Rochester, NY.

    PubMed

    Pichichero, Michael E

    2016-09-01

    This review summarizes a prospective, longitudinal 10-year study in Rochester, NY, involving 760 children where virtually all clinically diagnosed acute otitis media (AOM) was confirmed by bacterial culture of middle ear fluid. This review describes detection of otopathogens in middle ear fluid, nasopharyngeal (NP) otopathogen colonization patterns, AOM risk factor analysis, biomarkers of AOM and antibody responses to NP colonization by otopathogens. After licensure of PCV13, there was an immediate drop in AOM caused by Streptococcus pneumoniae (Spn) vaccine serotypes and shortly thereafer an increase in nonvaccine types 16, 21 and 35B. When NP co-colonization occurred, nontypeable Haemophilus influenzae (NTHi) predominated over Spn to cause AOM, and NTHi and Spn both predominated over Moraxella catarrhalis. Transcriptome analysis of peripheral blood mononuclear cells identified unique signatures for NTHi AOM compared with Spn AOM. Elevation of 3 cytokines in serum (S100A12, intercellular adhesion molecule 1 and interleukin 10) accurately predicted the presence and recovery from AOM and the likely otopathogen. NP colonization was an immunizing event. PMID:27182898

  17. Clinically Applicable Multiplex PCR for Four Middle Ear Pathogens

    PubMed Central

    Hendolin, Panu H.; Paulin, Lars; Ylikoski, Jukka

    2000-01-01

    The multiplex PCR method for the detection of Alloiococcus otitidis, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (P. H. Hendolin, A. Markkanen, J. Ylikoski, and J. J. Wahlfors, J. Clin. Microbiol. 35:2854–2858, 1997) in middle ear effusions (MEEs) was modified to be better suited for clinical use. To detect false-negative results, an internal amplification was added to the reaction, and to prevent carryover contamination, the dUTP–uracil-N-glycosidase system was incorporated into the procedure. Labor was minimized by using the heat-activatable AmpliTaq Gold polymerase in order to circumvent manual hot start and by detecting the amplification products on an automated sequencer. The performance of the improved protocol was verified with MEEs from patients with otitis media with effusion. In addition, a ligase detection reaction (LDR) was developed for confirmation of the PCR products. The modifications increased the reliability of the protocol and the hands-off time significantly. However, when two DNA extraction protocols were compared, gram-negative bacteria were detected more often in phenol-treated MEEs (94 versus 46%; P < 0.001), and gram-positive bacteria were detected more often in MEEs dissolved in sodium dodecyl sulfate-NaOH-chaotropic salt (83 versus 27%; P < 0.001). The LDR was found to be 100% specific. In all, the results demonstrate the feasibility of the rapid (7-h) multiplex PCR method for routine laboratory use. PMID:10618075

  18. [Use of transport medium in sputum bacterial culture examination of lower airway infection].

    PubMed

    Muraki, Masato; Kitaguchi, Sayako; Ichihashi, Hideo; Tsuji, Fumio; Ohmori, Takashi; Haraguchi, Ryuta; Tohda, Yuji

    2006-06-01

    Our medical institution does not have a bacterial culture facility, requiring outsourcing of bacterial culture tests. Due to the time elapsed from the time of specimen collection to culturing, the identification of causative bacteria in respiratory tract infections tends to be difficult. We therefore used transport medium for sputum bacteria examinations. Expectorated purulent or purulent-mucous sputum specimens were collected from 32 patients with lower respiratory tract infection. We divided each of the sputum specimens into the two treatment groups: transport medium (Seedswab gamma2) ndar and stad disinfection container. Paired samples prepared from each patient were sent out for bacterial culture together. The time elapsed from collection to delivery to the lab were as follows: day 0 (same day, n = 14 patients), day 1 (n = 15), day 2 (n = 2), and day 3 (n = 1). The identified causative bacteria were Streptococcus pneumoniae (n = 6 patients), Haemophilus influenzae (n =5), Pseudomonas aeruginosa (n = 4), Staphylococcus aureus (n = 2), Moraxella catarrhalis (n = 2), Klebsiella pneumoniae (n = 1), and Streptococcus agalactiae (n = 1). Samples prepared by each of the two methods gave similar results. The utility of transport medium for examination of general bacteria for lower airway infection from sputum samples was not demonstrated. The rate of detection of bacteria decreased, when the transport of samples was delayed. Therefore, we need to send the sputum specimens as quickly as possible. PMID:16841712

  19. Urethritis-associated Pathogens in Urine from Men with Non-gonococcal Urethritis: A Case-control Study.

    PubMed

    Frølund, Maria; Lidbrink, Peter; Wikström, Arne; Cowan, Susan; Ahrens, Peter; Jensen, Jørgen Skov

    2016-06-15

    The aetiology of non-gonococcal urethritis (NGU) remains unexplained in 30-40% of patients. Urine samples from men attending Swedish sexually transmitted disease clinics were examined by species-specific quantitative PCRs for Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, U. parvum, adenovirus, herpes simplex virus, Neisseria meningitidis, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. A total of 187 men with acute NGU (symptoms ≤ 30 days) and 24 with chronic NGU (symptoms < 30 days) were cases, and 73 men without NGU were controls. Number of lifetime sexual partners was negatively associated with U. urealyticum bacterial load. C. trachomatis and M. genitalium were associated with NGU, as was U. urealyticum, with bacterial loads ≥ 1.3 × 103 genome equivalents/ml urine. Virus and H. influenzae might explain a few NGU cases, but the aetiology in at least 24% of patients with acute NGU was unexplained. In multivariate analysis, detection of U. urealyticum was significantly more common in acute NGU (20%) compared with controls (11%). PMID:26658669

  20. In vitro activity of gemifloxacin against recent clinical isolates of bacteria in Korea.

    PubMed

    Yong, Dong Eun; Cheong, Hee-Jin; Kim, Yang Soo; Park, Yeon Joon; Kim, Woo-Joo; Woo, Jun Hee; Lee, Kyung Won; Kang, Moon Won; Choo, Youn-Sung

    2002-12-01

    Gemifloxacin is an enhanced-affinity fluoroquinolone with broad-spectrum antibacterial activity. In Korea, resistant bacteria are relatively more prevalent than in other industrialized countries. In this study, we studied the in vitro activities of gemifloxacin, gatifloxacin, moxifloxacin, levofloxacin, ciprofloxacin, and other commonly used antimicrobial agents against 1,689 bacterial strains isolated at four Korean university hospitals during 1999-2000. Minimum inhibitory concentrations (MICs) were determined using the agar dilution method of National Committee for Clinical Laboratory Standards. Gemifloxacin had the lowest MICs for the respiratory pathogens: 90% of Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were inhibited by 0.06, 0.03, and 0.03 mg/L, respectively. Gemifloxacin was more active than the other fluoroquinolones against methicillin-susceptible Staphylococcus aureus, coagulase-negative staphylococci, streptococci, and Enterococcus faecalis. The MIC90s of gemifloxacin for Klebsiella oxytoca, Proteus vulgaris, and non-typhoidal Salmonella spp. were 0.25, 1.0, and 0.12 mg/L, respectively, while those for other Gram-negative bacilli were 4-64 mg/L. In conclusion, gemifloxacin was the most active among the comparative agents against Gram-positive species, including respiratory pathogens isolated in Korea. PMID:12482994

  1. Discovery and analysis of 4H-pyridopyrimidines, a class of selective bacterial protein synthesis inhibitors.

    PubMed

    Ribble, Wendy; Hill, Walter E; Ochsner, Urs A; Jarvis, Thale C; Guiles, Joseph W; Janjic, Nebojsa; Bullard, James M

    2010-11-01

    Bacterial protein synthesis is the target for numerous natural and synthetic antibacterial agents. We have developed a poly(U) mRNA-directed aminoacylation/translation protein synthesis system composed of phenyl-tRNA synthetases, ribosomes, and ribosomal factors from Escherichia coli. This system, utilizing purified components, has been used for high-throughput screening of a small-molecule chemical library. We have identified a series of compounds that inhibit protein synthesis with 50% inhibitory concentrations (IC(50)s) ranging from 3 to 14 μM. This series of compounds all contained the same central scaffold composed of tetrahydropyrido[4,3-d]pyrimidin-4-ol (e.g., 4H-pyridopyrimidine). All analogs contained an ortho pyridine ring attached to the central scaffold in the 2 position and either a five- or a six-member ring tethered to the 6-methylene nitrogen atom of the central scaffold. These compounds inhibited the growth of E. coli, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with MICs ranging from 0.25 to 32 μg/ml. Macromolecular synthesis (MMS) assays with E. coli and S. aureus confirmed that antibacterial activity resulted from specific inhibition of protein synthesis. Assays were developed for the steps performed by each component of the system in order to ascertain the target of the compounds, and the ribosome was found to be the site of inhibition. PMID:20696870

  2. The antimicrobial activity of fruits from some cultivar varieties of Rubus idaeus and Rubus occidentalis.

    PubMed

    Krauze-Baranowska, M; Majdan, M; Hałasa, R; Głód, D; Kula, M; Fecka, I; Orzeł, A

    2014-10-01

    Raspberries, derived from different cultivar varieties, are a popular ingredient of everyday diet, and their biological activity is a point of interest for researchers. The ethanol-water extracts from four varieties of red (Rubus idaeus'Ljulin', 'Veten', 'Poranna Rosa') and black (Rubus occidentalis'Litacz') raspberries were evaluated in the range of their antimicrobial properties as well as phenolic content - sanguiin H-6, free ellagic acid and anthocyanins. The antimicrobial assay was performed with the use of fifteen strains of bacteria, both Gram-negative and Gram-positive. The antimicrobial activity of the extracts varied and depended on the analysed strain of bacteria and cultivar variety, with the exception of Helicobacter pylori, towards which the extracts displayed the same growth inhibiting activity. Two human pathogens Corynebacterium diphtheriae and Moraxella catarrhalis proved to be the most sensitive to raspberry extracts. Contrary to the extracts, sanguiin H-6 and ellagic acid were only active against eight and nine bacterial strains, respectively. The determined MIC and MBC values of both compounds were several times lower than the tested extracts. The highest sensitivity of Corynebacterium diphtheriae to extracts from both black and red raspberries may be due to its sensitivity to sanguiin H-6 and ellagic acid. PMID:25131001

  3. Bronchiectasis: a bacteriological profile

    PubMed Central

    Bopaka, Régis Gothard; El Khattabi, Wiam; Janah, Hind; Jabri, Hasna; Afif, Hicham

    2015-01-01

    The occurrence of bronchiectasis can involve a combination of many environmental factors, including infection. The aim of our work is to determine the bacteriological profile of bronchiectasis. This is a retrospective study of 100 patients hospitalized in between January 2010 and July 2013. The average age was 48 years with a 58% female predominance. Symptomatology was by a bronchial syndrome in 90% of cases. Bacteriological examination was able to isolate the microbe in 35% of cases. In our study it was through the examination of sputum cytology in 27% of cases, through the examination of liquid bronchial aspiration in 5% of cases, and through direct examination of sputum in search of Mycobacterium tuberculosis in 3% of cases. Microbes isolated were: Streptococcus pneumonia in 11 cases; Pseudomonas aeruginosa in 10 cases, Klebsiella pneumonia and Mycobacterium tuberculosis in 3 cases each; Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Citrobacter spp, Serratia marcescens, Mycoplasma pneumoniae, Acinetobacter baumannii and Staphylococcus aureus in one case each. Through this work, the authors highlight that Streptococcus pneumoniae and Pseudomonas aeruginosa are the most commonly- identified microbes in their patients. It is necessary to have a full bacterial examination and to repeat it regularly over the course of the bronchiectasis. PMID:27047618

  4. Pharmacologic characteristics of prulifloxacin.

    PubMed

    Matera, Maria Gabriella

    2006-01-01

    Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum oral fluoroquinolone antibacterial agent. After absorption, prulifloxacin is metabolized by esterases to ulifloxacin. The drug has a long elimination half-life, allowing once-daily administration. In vitro, ulifloxacin is generally more active than other fluoroquinolones against a variety of clinical isolates of Gram-negative bacteria, including community and nosocomial isolates of Escherichia coli, Klebsiella spp., Proteus, Providencia and Morganella spp., Moraxella catarrhalis, Haemophilus spp., and Pseudomonas aeruginosa. Gram-positive organisms, including methicillin- or oxacillin-susceptible Staphylococcus aureus, Enterococcus spp. and Streptococcus pneumoniae, are susceptible to ulifloxacin. In well-designed clinical trials, prulifloxacin showed good clinical and bacteriological efficacy (similar to that of ciprofloxacin) and was generally well tolerated, demonstrating a similar tolerability profile to that of ciprofloxacin. In conclusion, the in vitro inhibitory and bactericidal activities exhibited by ulifloxacin and the favorable characteristics shown by its prodrug (prulifloxacin) in clinical trials, particularly indicate this drug for the treatment of lung and urinary infections. PMID:16360331

  5. Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate.

    PubMed

    Sader, Helio S; Jacobs, Michael R; Fritsche, Thomas R

    2007-03-01

    The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, cephalexin) and amoxicillin/clavulanate are reviewed. These beta-lactam agents have been widely used in the outpatient arena for the treatment of community-acquired respiratory tract and other mild-to-moderate infections. The data presented here were obtained from critical review articles on each of these compounds. Cephalexin and cefaclor were among the least potent and had the narrowest antimicrobial spectrums against the pathogens evaluated. In contrast, cefdinir, cefpodoxime, cefprozil, and cefuroxime were highly active against penicillin-susceptible Streptococcus pneumoniae and retained some activity against penicillin-intermediate strains, whereas amoxicillin/clavulanate was the most active against S. pneumoniae, including most penicillin nonsusceptible strains. Amoxicillin/clavulanate and cefdinir were the most potent compounds against methicillin (oxacillin)-susceptible Staphylococcus aureus, whereas cefpodoxime was the most potent compound against Haemophilus influenzae. Amoxicillin/clavulanate, cefdinir, and cefpodoxime were also active against Moraxella catarrhalis, including beta-lactamase-producing strains. In summary, orally administered "3rd-generation" or extended spectrum cephalosporins exhibited more balanced spectrums of activity against the principal bacterial pathogens responsible for outpatient respiratory tract and other infections when compared with other widely used oral cephalosporins of earlier generations or amoxicillin alone. PMID:17292577

  6. Restriction-Modification systems interplay causes avoidance of GATC site in prokaryotic genomes.

    PubMed

    Ershova, Anna; Rusinov, Ivan; Vasiliev, Mikhail; Spirin, Sergey; Karyagina, Anna

    2016-04-01

    Palindromes are frequently underrepresented in prokaryotic genomes. Palindromic 5[Formula: see text]-GATC-3[Formula: see text] site is a recognition site of different Restriction-Modification (R-M) systems, as well as solitary methyltransferase Dam. Classical GATC-specific R-M systems methylate GATC and cleave unmethylated GATC. On the contrary, methyl-directed Type II restriction endonucleases cleave methylated GATC. Methylation of GATC by Dam methyltransferase is involved in the regulation of different cellular processes. The diversity of functions of GATC-recognizing proteins makes GATC sequence a good model for studying the reasons of palindrome avoidance in prokaryotic genomes. In this work, the influence of R-M systems and solitary proteins on the GATC site avoidance is described by a mathematical model. GATC avoidance is strongly associated with the presence of alternate (methyl-directed or classical Type II R-M system) genes in different strains of the same species, as we have shown for Streptococcus pneumoniae, Neisseria meningitidis, Eubacterium rectale, and Moraxella catarrhalis. We hypothesize that GATC avoidance can result from a DNA exchange between strains with different methylation status of GATC site within the process of natural transformation. If this hypothesis is correct, the GATC avoidance is a sign of a DNA exchange between bacteria with different methylation status in a mixed population. PMID:26972562

  7. Mouse Models for the Study of Mucosal Vaccination Against Otitis Media

    PubMed Central

    Sabirov, Albert; Metzger, Dennis W.

    2008-01-01

    Otitis media (OM) is one of the most common infectious diseases in humans. The pathogenesis of OM involves nasopharyngeal colonization (NP) and retrograde ascension of the pathogen up the Eustachian tube into the middle ear (ME). Due to increasing rates of antibiotic resistance, there is an urgent need for vaccines to prevent infections caused by the most common causes of bacterial OM, including nontypeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Current vaccine strategies aim to diminish bacterial NP carriage, thereby reducing the likelihood of developing acute OM. To be effective, vaccination should induce local mucosal mmunity both in the ME and in the NP. Studies in animal models have demonstrated that the intranasal route of vaccination is particularly effective at inducing immune responses in the nasal passage and ME for protection against OM. The mouse is increasingly used in these models, because of the availability of murine reagents and the existence of technology to manipulate murine models of disease immunologically and genetically. Previous studies confirmed the suitability of the mouse as a model for inflammatory processes in acute OM. Here, we discuss various murine models of OM and review the applicability of these models to assess the efficacy of mucosal vaccination and the mechanisms responsible for protection. In addition, we discuss various mucosal vaccine antigens, mucosal adjuvants and mucosal delivery systems. PMID:18295938

  8. Antimicrobial activity of preparation Bioaron C.

    PubMed

    Gawron-Gzella, Anne; Michalak, Anna; Kędzia, Anna

    2014-01-01

    The antimicrobial activity of sirupus Bioaron C, a preparation, whose main ingredient is an extract from the leaves of Aloe arborescens, was tested against different microorganisms isolated from patients with upper respiratory tract infections. The experiments were performed on 40 strains: 20 strains of anaerobic bacteria, 13 strains of aerobic bacteria and 7 strains of yeast-like fungi from the genus Candida and on 18 reference strains (ATCC). The antimicrobial activity of Bioaron C (MBC and MFC) was determined at undiluted concentration. Bioaron C proved to be very effective against the microorganisms causing infections. At the concentration recommended by the producer, the preparation showed biocidal activity (MBC, MFC) against the strains of the pathogenic microorganisms, which cause respiratory infections most frequently, including, among others, Peptostreptococcus anaerobius, Parvimonas micra, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus anginosus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa and Candida albicans, already after 15 min. The MIC of Bioaron C against most of the tested microorganisms was 5 to 100 times lower than the usually applied concentration. The great antimicrobial activity means that the preparation may be used in the prevention and treatment of infections of the upper respiratory tract. Bioaron C may be an alternative or complement to classical therapy, especially in children. PMID:25362808

  9. Identification of bacteria causing acute otitis media using Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Ayala, Oscar D.; Wakeman, Catherine A.; Skaar, Eric P.; Mahadevan-Jansen, Anita

    2016-03-01

    Otitis media (OM) is the leading cause of acute physician visits and prescription of antibiotics for children. Current standard techniques to diagnose acute otitis media (AOM) are limited by their ability to probe only changes in symptoms of the bacterial infection that cause AOM. Furthermore, they are not able to detect the presence of or identify bacteria causing AOM, which is important for diagnosis and proper antibiotic treatment. Our goal is to detect the presence of and identify the pathogens involved in causing AOM based on their biochemical profile using Raman spectroscopy (RS). An inVia confocal Raman microscope (Renishaw) at 785 nm was used to detect bacteria causing AOM in vitro. The three main bacteria that cause AOM, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae were cultured in chocolate agar and Mueller-Hinton agar to determine which agar type would minimize Raman signal from the growth agar. Preliminary results identified specific Raman spectral features characteristic of S. pneumoniae. RS has the potential to accurately diagnose AOM, which will help in identifying the antibiotic that will be most beneficial for the patient and ultimately decrease the course of infection.

  10. [Antimicrobial spectrum of ceftaroline. In vitro activity against methicillin-resistant staphylococci].

    PubMed

    Cercenado, Emilia; Morosini, María Isabel

    2014-03-01

    Because of the increase in bacterial resistance, there is a need for new antimicrobial agents. In particular, Staphylococcus aureus is a frequent cause of severe infections and has an extraordinary capacity to develop antibiotic multiresistance, including resistance to glycopeptides, linezolid, and daptomycin. Although the incidence of methicillin-resistant S. aureus (MRSA) seems to have stabilized in the last few years, its wide dissemination in healthcare settings and in the community is a cause of concern. Ceftaroline is a new broad-spectrum cephalosporin with bactericidal activity against Gram-positive bacteria, including MRSA and multidrug-resistant Streptococcus pneumoniae. In addition, this drug is active against staphylococci showing resistance to glycopeptides, linezolid, and daptomycin. The ceftaroline MIC90 against MRSA ranges from 0.5-2mg/L and that against methicillin-resistant coagulase-negative staphylococci is 0.5mg/L. Ceftaroline has also good activity against respiratory pathogens including Haemophilus influenzae and Moraxella catarrhalis. Although this drug is active against Enterobacteriaceae, it does not retain activity when these isolates produce extended-spectrum beta-lactamases, carbapenemases or hyperproduce AmpC. Ceftaroline is not active against nonfermentative Gram-negative bacilli. Ceftaroline is an interesting addition to the therapeutic armamentarium against MRSA and constitutes an important option for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive microorganisms. PMID:24702973

  11. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  12. Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

    PubMed Central

    Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

    2015-01-01

    Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

  13. Targeting of Neisserial PorB to the mitochondrial outer membrane: an insight on the evolution of β-barrel protein assembly machines.

    PubMed

    Jiang, Jhih-Hang; Davies, John K; Lithgow, Trevor; Strugnell, Richard A; Gabriel, Kipros

    2011-11-01

    Mitochondria originated from Gram-negative bacteria through endosymbiosis. In modern day mitochondria, the Sorting and Assembly Machinery (SAM) is responsible for eukaryotic β-barrel protein assembly in the mitochondrial outer membrane. The SAM is the functional equivalent of the β-barrel assembly machinery found in the outer membrane of Gram-negative bacteria. In this study we examined the import pathway of a pathogenic bacterial protein, PorB, which is targeted from pathogenic Neisseria to the host mitochondria. We have developed a new method for measurement of PorB assembly into mitochondria that relies on the mobility shift exhibited by bacterial β-barrel proteins once folded and separated under semi-native electrophoretic conditions. We show that PorB is targeted to the outer mitochondrial membrane with a dependence on the intermembrane space shuttling chaperones and the core component of the SAM, Sam50, which is a functional homologue of BamA that is required for PorB assembly in bacteria. The peripheral subunits of the SAM, Sam35 and Sam37, which are essential for eukaryotic β-barrel protein assembly but do not have distinguishable functional homologues in bacteria, are not required for PorB assembly in eukaryotes. This shows that PorB uses an evolutionary conserved 'bacterial like' mechanism to infiltrate the host mitochondrial outer membrane. PMID:22032638

  14. Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines.

    PubMed

    Rouppe van der Voort, E M; Kuipers, B; Brugghe, H F; van Unen, L M; Timmermans, H A; Hoogerhout, P; Poolman, J T

    1997-03-01

    Synthetic peptides derived from the predicted loops 1 and 4 of meningococcal PorA, sero-subtype P1.7,16, were used to study the epitope specificity of murine and human PorA P1.7,16 bactericidal antibodies. The predicted loops 1 and 4 are surface exposed and carry in their apices the sero-subtype epitopes P1.7 (loop 1) or P1.16 (loop 4), respectively. Peptides were synthesized as mono- and multimeric peptides. Murine monoclonal and polyclonal antibodies were induced with meningococcal whole cell preparations. Polyclonal antibodies were evoked in volunteers after one immunization with 50 micrograms or 100 micrograms protein of a hexavalent meningococcal PorA vesicle vaccine. The induction of PorA antibodies was determined in ELISA using purified PorA P1.7,16. The epitope specificity of anti-PorA antibodies for both murine and human antibodies could be demonstrated by direct peptide ELISA using overlapping multimeric peptides almost spanning the entire loops 1 or 4 of the protein. The capacity of peptides to inhibit the bactericidal activity of murine and human antibodies was investigated using meningococcal strain H44/76 (B:15:P1.7,16) as a target strain. Bactericidal activities could be inhibited with both monomeric and multimeric peptides derived from epitopes P1.7 and P1.16. PMID:9093834

  15. Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

    2011-12-01

    A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOURĀO, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

  16. AMPEROMETRIC MICROBIAL BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS USING RECOMBINANT MORAXELLA SP. WITH SURFACE EXPRESSED ORGANOPHOSPHORUS HYDROLASE. (R828160)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  17. Comparison of the efficacy and safety of faropenem daloxate and cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in adults.

    PubMed

    Siegert, Ralf; Berg, Olof; Gehanno, Pierre; Leiberman, Alberto; Martinkenas, Jonas Laimutis; Nikolaidis, Paul; Arvis, Pierre; Alefelder, Melody; Reimnitz, Peter

    2003-04-01

    In this multicentre, multinational, comparative, double-blind clinical trial, outpatients with both clinical signs and symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive for 7 days either a twice-daily oral regimen of faropenem daloxate (300 mg) or a twice daily oral regimen of cefuroxime axetil (250 mg). Among 452 patients considered valid for clinical efficacy, faropenem daloxate treatment was found to be statistically equivalent to cefuroxime axetil (89.0% vs. 88.4%-95% CI=-5.2%; +6.4%) at the 7-16 days post-therapy assessment. At 28-35 days post-therapy, the continued clinical cure rate in the faropenem daloxate group was 92.6% and that for the cefuroxime axetil group was 94.9% (95% CI: -6.8%; +1.2%). A total of 148 organisms was obtained in 136 microbiologically valid patients (30.1%). The predominant causative organisms were Streptococcus pneumoniae (47.1%), Haemophilus influenzae (30.1%), Staphylococcus aureus (14.7%) and Moraxella catarrhalis (8.8%). The bacteriological success rate at the 7-16 days post-therapy evaluation was similar in both treatment groups: 91.5% and 90.8% in the faropenem daloxate and cefuroxime axetil groups, respectively (95% CI=-9.2%; +9.5%). Eradication or presumed eradication was detected for 97.3% and 96.3% of S. pneumoniae, 85.0% and 90.5% of H. influenzae, 88.9% and 90.9% of S. aureus and 100.0% and 83.3% of M. catarrhalis in faropenem daloxate and cefuroxime axetil recipients, respectively. At least one drug-related event was reported by 9.5% of the faropenem daloxate-treated patients and by 10.3% of those who received cefuroxime axetil. The most frequently reported drug-related events were diarrhoea (2.2% versus 2.9%), nausea/vomiting (1.5% vs. 0.7%), abdominal pain (0.7% vs 1.5%) and skin reactions (1.5% vs. 1.1%). Overall, faropenem daloxate was at least as effective clinically and bacteriologically as cefuroxime axetil and was well tolerated. PMID:12709801

  18. Results of the 1997 SENTRY Antimicrobial Surveillance Program in Three Brazilian Medical Centers.

    PubMed

    Sader; Sampaio; Zoccoli; Jones

    1999-04-01

    The SENTRY Antimicrobial Surveillance Program began in January, 1997, and is designed to monitor nosocomial and selected community acquired infections via a worldwide surveillance network of sentinel hospitals distributed equally by geographic location and size. Three sites in Brazil - Rio de Janeiro, Florianópolis, and São Paulo - participated in the SENTRY Antimicrobial Surveillance Program stet. Rank order of occurrence and antimicrobial susceptibility of pathogenic species causing bloodstream infections, pneumonia, wound or skin and soft tissue infections, and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time. Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained from outpatients with respiratory tract infections were also evaluated. The isolates for the evaluated infections were: 1) bloodstream - 20 consecutive isolates in each calendar month during a 12-month period; 2) pneumonia - 100 consecutive isolates over a 6 month period; 3) wound or skin and soft tissue - 50 consecutive isolates over a 3 month period; and 4) UTI - 50 consecutive isolates over a 3 month period. Each hospital also contributed, over a 6 month period, consecutive clinically significant outpatient isolates (one isolate per patient) of S. pneumoniae, H. influenzae, and M. catarrhalis that were considered pathogens in respiratory tract infections. Data collected for each isolate included species identification, antimicrobial susceptibility profile, date of isolation, and specimen type. Molecular studies were performed on selected isolates. A total of 1,241 bacterial strains were obtained; the majority were cultured from hospitalized patients, while 139 were fastidious organisms from community acquired respiratory tract infections. Gram-negative bacilli and S. aureus were the predominant pathogens, and Enterobacter spp. was a significant

  19. Antimicrobial characterisation of CEM-101 activity against respiratory tract pathogens, including multidrug-resistant pneumococcal serogroup 19A isolates.

    PubMed

    Farrell, David J; Sader, Helio S; Castanheira, Mariana; Biedenbach, Douglas J; Rhomberg, Paul R; Jones, Ronald N

    2010-06-01

    CEM-101 is a novel fluorinated macrolide-ketolide with potent activity against bacterial pathogens that are susceptible or resistant to other macrolide-lincosamide-streptogramin B (MLS(B))-ketolide agents. CEM-101 is being developed for oral and parenteral use in moderate to moderately severe community-acquired bacterial pneumonia. The objective of this study was to assess the activity of CEM-101 and comparators against contemporary respiratory tract infection (RTI) isolates. A worldwide sample of organisms was used, including Streptococcus pneumoniae [n=168; 59.3% erythromycin-resistant and 18 multidrug-resistant (MDR) serogroup 19A strains], Moraxella catarrhalis (n=21; 11 beta-lactamase positive), Haemophilus influenzae (n=100; 48 beta-lactamase positive), Haemophilus parainfluenzae and Haemophilus haemolyticus (n=12), and Legionella pneumophila (n=30). Testing and interpretation were performed using reference Clinical and Laboratory Standards Institute methods. CEM-101 was very potent against S. pneumoniae [minimum inhibitory concentration for 90% of the organisms (MIC90)=0.25 mg/L; highest MIC at 0.5 mg/L] and was 2- and > or =32-fold more active than telithromycin and clindamycin, respectively. CEM-101 also demonstrated potent activity against S. pneumoniae MDR-19A strains (MIC90=0.5 mg/L). CEM-101 was the most potent antimicrobial agent tested against L. pneumophila, with all MIC values at < or = 0.015 mg/L (telithromycin MIC90=0.03 mg/L). CEM-101 was as potent as azithromycin against Haemophilus spp. RTI pathogens (MIC90=2 mg/L), with no variations for beta-lactamase production. CEM-101 MIC values against M. catarrhalis were all at < or =0.5mg/L. Interestingly, CEM-101 potency was ca. 6 log(2) dilutions greater than telithromycin MIC results among 44 beta-haemolytic streptococci having telithromycin MICs > or = 2 mg/L. CEM-101 exhibited the greatest potency and widest spectrum of activity against RTI pathogens among the tested MLS(B)-ketolide agents

  20. Longitudinal Nasopharyngeal Carriage and Antibiotic Resistance of Respiratory Bacteria in Indigenous Australian and Alaska Native Children with Bronchiectasis

    PubMed Central

    Hare, Kim M.; Singleton, Rosalyn J.; Grimwood, Keith; Valery, Patricia C.; Cheng, Allen C.; Morris, Peter S.; Leach, Amanda J.; Smith-Vaughan, Heidi C.; Chatfield, Mark; Redding, Greg; Reasonover, Alisa L.; McCallum, Gabrielle B.; Chikoyak, Lori; McDonald, Malcolm I.; Brown, Ngiare; Torzillo, Paul J.; Chang, Anne B.

    2013-01-01

    Background Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations. Methods Indigenous children aged 0.5–8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004–8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year. Results Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005–6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004–6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a ‘cumulative dose-response’ relationship. Conclusions

  1. Etiological characteristics of chlamydia trachoma conjunctivitis of Primary Boarding School students in the Qinghai Tibetan area.

    PubMed

    Wang, Mei; Lu, Xinxin; Hu, Ailian; Zhang, Mingxin; Li, Xue; Deng, Shijing; Wang, Ningli

    2016-06-01

    The aim of this study was to investigate the etiological characteristics of Chlamydia trachomatis conjunctivitis among resident students at primary schools in the Qinghai Tibetan area in order to understand the distribution of C. trachomatis and other pathogenic microorganisms, to detect the isolation rate of infectious pathogens, and to provide an evidence for further targeted efforts in the prevent of sporadic trachoma efforts. From two primary schools in Qinghai Province, ocular samples from 35 students who were clinically diagnosed as trachoma cases and 60 normal controls were obtained by swabbing their upper eyelids and lower conjunctival sacs. Samples were preserved at 4°C and airlifted to Beijing Tongren Hospital within 24 h. Real- time polymerase chain reaction (RT-PCR) was used to screen for C. trachomatis, and nested PCR was used to amplify a fragment of the ompA gene for serotype confirmation. Bacterial cultivation and sensitivity tests were conducted based on the 2015 version of the Clinical and Laboratory Standards Institute. Adenovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were screened by RT-PCR. Among the 35 students with trachoma, 8 came from the Jianshetang Primary School and 27 came from the Central Primary School. Two novel C. trachomatis B serotypes (GenBank accession numbers KU737520 and KU737521) were detected based on a sequence analysis of the ompA gene. Single C. trachomatis infections accounted for 42.86% (9/21) of the cases, and infections with multiple bacteria, particularly Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae, accounted for the remaining 57.14% (12/21). Of the 14 C. trachomatis-negative samples, one was positive for adenoviral infection (serotype D) and 13 were positive for bacterial infections (H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, streptococci other than S. pneumoniae, Staphylococcus epidermidis, Corynebacterium, and

  2. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France

    PubMed Central

    2012-01-01

    Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion The carriage

  3. Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

    PubMed

    Cartwright, K; Morris, R; Rümke, H; Fox, A; Borrow, R; Begg, N; Richmond, P; Poolman, J

    1999-06-01

    The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation. PMID:10418910

  4. Crystallization and preliminary X-ray analysis of the C-terminal fragment of PorM, a subunit of the Porphyromonas gingivalis type IX secretion system.

    PubMed

    Stathopulos, Julien; Cambillau, Christian; Cascales, Eric; Roussel, Alain; Leone, Philippe

    2015-01-01

    PorM is a membrane protein involved in the assembly of the type IX secretion system (T9SS) from Porphyromonas gingivalis, a major bacterial pathogen responsible for periodontal disease in humans. The periplasmic domain of PorM was overexpressed in Escherichia coli and purified. A fragment of the purified protein was obtained by limited proteolysis. Crystals of this fragment belonged to the tetragonal space group P4(3)2(1)2. Native and MAD data sets were recorded to 2.85 and 3.1 Å resolution, respectively, using synchrotron radiation. PMID:25615973

  5. "Estudio tribologico de aceros para moldes. Aplicacion al moldeo por inyeccion de polibutilentereftalato reforzado con fibra de vidrio"

    NASA Astrophysics Data System (ADS)

    Martinez Mateo, Isidoro Jose

    Mould materials for injection moulding of polymers and polymer-matrix composites represent a relevant industrial economic sector due to the large quantity of pieces and components processed. The material selection for mould manufacturing, its composition and heat treatment, the hardening procedures and machining and finishing processes determine the service performance and life of the mould. In the first part of the present study, the relationship between the hardness and microstructure and the wear resistance of mould steels from large blocks has been studied by pin-on-disc tests, studying the main wear mechanisms. In order to determine the surface damage on mould steels under real injection conditions, different commercial steels have been studied by measuring the variation of surface roughness with the number of injected pieces with different reinforcement percentages and different mould geometries, by using optical profilometry and scanning electron microscopy techniques. It was important to determine the variation of surface roughness of the moulded pieces with the number of injection operations. The materials used were polybutyleneterephthalate pure and reinforced with either 20% or 50% glass fibre. For the different mould designs, the evolution of the glass fibre orientation with injection flow has been determined by image analysis and related to roughness changes and surface damage, both of the composite parts and of the mould steel surface. Finally, the abrasion resistance of the composite parts has been studied by scratch tests as a function of the number of injected parts and of the scratch direction with respect to injection flow and glass fibre orientation. Los materiales para moldes de inyeccion de polimeros y materiales compuestos representan un sector economicamente muy relevante debido al gran aumento del numero de componentes fabricados a partir de materiales polimericos obtenidos mediante moldeo por inyeccion. La seleccion del material para la

  6. P(O)R2-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

    PubMed Central

    Hu, Rong-Bin; Wang, Hong-Li; Zhang, Hong-Yu; Zhang, Heng; Ma, Yan-Na

    2014-01-01

    Summary Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized products are produced with good enantioselectivity. PMID:25246966

  7. Adult Student Retention and Achievement with Language-Based Modular Materials. POR FIN: Program Organizing Related Family Instruction in the Neighborhood.

    ERIC Educational Resources Information Center

    Bexar County School Board, San Antonio, TX.

    The goal of the POR FIN research design was to develop a language-based curriculum emphasizing the audiolingual approach and integrating academic and social-functioning subject matter. The modular curriculum is designed so that each lesson is independent and complete in itself, and provides a high degree of motivation, retention, and achievement…

  8. Informe a la nación indica que los índices de muertes por cáncer siguen bajando

    Cancer.gov

    Los índices de mortalidad por todos los cánceres combinados para hombres, mujeres y niños siguieron bajando en Estados Unidos entre 2004 y 2008, según el Informe Anual a la Nación sobre el Estado del Cáncer de 1975 a 2008. El índice general de diagnóstico

  9. El proceso hacia la integracion de la equidad por genero al curriculo.(The Process of the Integration of Gender Equity in the Curriculum.)

    ERIC Educational Resources Information Center

    Rivera-Bermudez, Carmen D.

    "El Proyecto Colaborativo de Equidad por Genero en la Educacion," or the Collaborative Project for Gender Equity in Education, was undertaken in Puerto Rico between 1990 and 1992 to study how to facilitate the integration of gender equity themes in the curriculum through the direct action of participating teachers. A study examined the attitudes…

  10. Community-based education in nutrition and cancer: the Por La Vida Cuidándome curriculum.

    PubMed

    Navarro, A M; Rock, C L; McNicholas, L J; Senn, K L; Moreno, C

    2000-01-01

    The Por La Vida (PLV) intervention model relies on community lay health advisors trained to conduct education sessions among members of their existing social networks. PLV Cuidándome was funded by the NCI to develop, implement, and evaluate the PLV model with respect to nutrition and cancer prevention, as well as early detection of breast and cervical cancers. The target population is the Latino community, for which substantial barriers to health care access exist. This article presents the curriculum that guides the sessions and describes its development, which was based on semi-structured interviews with Latina lay-health community workers to explore relevant attitudes and behaviors. Also key to the process was the work of the educational materials committee, whose members offered community representation as well as expertise in nutritional sciences, educational technologies, and community-based health promotion interventions and research. The 12-session curriculum's goal was to increase both the variety and the quality of fruits and/or vegetables consumed. It included information about consumption of fiber and fat in the importance of balance between energy intake and physical activity. The program has been well received. An ongoing study examines how it enhances nutrition and cancer prevention. PMID:11019766

  11. Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

    PubMed Central

    Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

    2010-01-01

    OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

  12. Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections.

    PubMed

    Bruhn, David F; Waidyarachchi, Samanthi L; Madhura, Dora B; Shcherbakov, Dimitri; Zheng, Zhong; Liu, Jiuyu; Abdelrahman, Yasser M; Singh, Aman P; Duscha, Stefan; Rathi, Chetan; Lee, Robin B; Belland, Robert J; Meibohm, Bernd; Rosch, Jason W; Böttger, Erik C; Lee, Richard E

    2015-05-20

    The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. A series of N-benzyl-substituted 3'-(R)-3'-aminomethyl-3'-hydroxy spectinomycins was developed on the basis of a computational analysis of the aminomethyl spectinomycin binding site and structure-guided synthesis. These compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against the common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Moraxella catarrhalis, as well as the sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis. Non-ribosome-binding 3'-(S) isomers of the lead compounds demonstrated weak inhibitory activity in in vitro protein translation assays and poor antibacterial activity, indicating that the antibacterial activity of the series remains on target against the ribosome. Compounds also demonstrated no mammalian cytotoxicity, improved microsomal stability, and favorable pharmacokinetic properties in rats. The lead compound from the series exhibited excellent chemical stability superior to spectinomycin; no interaction with a panel of human receptors and drug metabolism enzymes, suggesting low potential for adverse reactions or drug-drug interactions in vivo; activity in vitro against a panel of penicillin-, macrolide-, and cephalosporin-resistant S. pneumoniae clinical isolates; and the ability to cure mice of fatal pneumococcal pneumonia and sepsis at a dose of 5 mg/kg. Together, these studies indicate that N-benzyl aminomethyl spectinomycins are suitable for further development to treat drug-resistant respiratory tract and sexually transmitted bacterial infections. PMID:25995221

  13. Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals.

    PubMed

    Fujimoto, Koichi; Takemoto, Koji; Hatano, Kazuo; Nakai, Toru; Terashita, Shigeyuki; Matsumoto, Masahiro; Eriguchi, Yoshiro; Eguchi, Ken; Shimizudani, Takeshi; Sato, Kimihiko; Kanazawa, Katsunori; Sunagawa, Makoto; Ueda, Yutaka

    2013-02-01

    SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC(90)s of ≤ 1 μg/ml. Unlike tebipenem (MIC(50), 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC(50), ≥ 128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their in vitro activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae, have low selective pressure on antipseudomonal

  14. Aminomethyl Spectinomycins as Novel Therapeutics for Drug Resistant Respiratory Tract and Sexually Transmitted Bacterial Infections

    PubMed Central

    Madhura, Dora B.; Shcherbakov, Dimitri; Zheng, Zhong; Liu, Jiuyu; Abdelrahman, Yasser M.; Singh, Aman P.; Duscha, Stefan; Rathi, Chetan; Lee, Robin B.; Belland, Robert J.; Meibohm, Bernd; Rosch, Jason W.; Böttger, Erik C.; Lee, Richard E.

    2015-01-01

    The antibiotic spectinomycin is a potent inhibitor of bacterial protein synthesis with a unique mechanism of action and an excellent safety index, but it lacks antibacterial activity against most clinically important pathogens. A novel series of N-benzyl substituted 3'-(R)- 3'-aminomethyl-3'-hydroxy spectinomycins was developed based on a computational analysis of the aminomethyl spectinomycin binding site and structure guided synthesis. These compounds had ribosomal inhibition values comparable to spectinomycin but showed increased potency against common respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Moraxella catarrhalis as well as the sexually transmitted bacteria Neisseria gonorrhoeae and Chlamydia trachomatis. Non-ribosome binding 3'-(S) isomers of the leads demonstrated weak inhibitory activity in in vitro protein translation assays and poor antibacterial activity, indicating that the antibacterial activity of the series remains on target. In addition to improved antibacterial potency, compounds also demonstrated no mammalian cytotoxicity, improved microsomal stability, and favorable pharmacokinetic properties in rats. The lead compound from the series, compound 1, exhibited excellent chemical stability, which was superior to spectinomycin and had no significant interaction with a panel of human receptors and drug metabolism enzymes suggesting low potential for adverse reactions or drug-drug interactions in vivo. Compound 1 was active in vitro against a panel of penicillin, macrolide, and cephalosporin resistant S. pneumoniae clinical isolates and cured mice of fatal pneumococcal pneumonia and sepsis at a dose of 5 mg/kg. Together, these studies indicate N-benzyl aminomethyl spectinomycins possess suitable properties for further development as novel antibacterial agents to treat drug resistant respiratory tract and sexually transmitted bacterial infections. PMID:25995221

  15. The in-vitro activity of faropenem, a novel oral penem.

    PubMed

    Woodcock, J M; Andrews, J M; Brenwald, N P; Ashby, J P; Wise, R

    1997-01-01

    The in-vitro activity of faropenem, a novel oral penem, was studied in comparison with other beta-lactam antimicrobials against 711 recent clinical isolates including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that faropenem was active against most members of the Enterobacteriaceae (MICs < or = 4 mg/L), with reduced activity against Serratia spp. (MIC90 = 32 mg/L). In common with its comparators, faropenem had weak activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia (MIC > 128 mg/L). Faropenem was active against staphylococci, although for MRSA MICs were raised (MIC90 = 2 mg/L) compared with those for MSSA (MIC90 = 0.12 mg/L). Faropenem was also found to be active against streptococci, Neisseria spp., Enterococcus faecalis and beta-lactamase-producing and non-producing strains of Haemophilus influenzae and Moraxella catarrhalis. Of the anaerobic bacteria studied, faropenem was most active against peptostreptococci and Clostridium perfringens (MIC90 < or = 1 mg/L) and Bacteroides fragilis (MIC90 = 4 mg/L). An increase in inoculum from 10(4) to 10(6) cfu raised faropenem MICs for Morganella morganii from 0.06-1 mg/L to 2-4 mg/L and for MRSA from 0.25-2 mg/L to 8 mg/L (a similar increase was not observed for MSSA). The MICs of faropenem were not affected by the presence of either 20% or 70% (v/v) serum. MICs for faropenem to 11 well characterized beta-lactamase producers were similar to those of non-producers. In hydrolysis studies, faropenem was shown to be highly stable to a number of beta-lactamases, including TEM-1, SHV-1, the extended spectrum beta-lactamases, TEM-3 and TEM-9, and the beta-lactamase produced by Staphylococcus aureus (NCTC 11561). PMID:9044026

  16. Ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia.

    PubMed

    Mpenge, Mbiye A; MacGowan, Alasdair P

    2015-01-01

    Ceftaroline is a new parenteral cephalosporin approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft tissue infections (cSSTIs) including those due to methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has broad-spectrum activity against gram-positive and gram-negative bacteria and exerts its bactericidal effects by binding to penicillin-binding proteins (PBPs), resulting in inhibition of bacterial cell wall synthesis. It binds to PBP 2a of MRSA with high affinity and also binds to all six PBPs in Streptococcus pneumoniae. In in vitro studies, ceftaroline demonstrated potent activity against Staphylococcus aureus (including MRSA and vancomycin-intermediate isolates), Streptococcus pneumoniae (including multidrug resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, and many common gram-negative pathogens, excluding extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa. In Phase II and Phase III clinical trials, ceftaroline was noninferior to its comparator agents and demonstrated high clinical cure rates in the treatment of cSSTIs and CAP. It demonstrated favorable outcomes in patients treated for both regulatory-approved indications and unlicensed indications in a retrospective analysis. Ceftaroline is a safe and effective option for treatment in specific patient populations in which its efficacy and safety have been proven. This article reviews the challenges in the treatment of cSSTI and CAP, ceftaroline and its microbiology, pharmacology, efficacy, and safety data which support its use in treatment of cSSTIs and CAP. PMID:25897241

  17. Pharmacokinetic/pharmacodynamic analysis to evaluate ceftaroline fosamil dosing regimens for the treatment of community-acquired bacterial pneumonia and complicated skin and skin-structure infections in patients with normal and impaired renal function.

    PubMed

    Canut, A; Isla, A; Rodríguez-Gascón, A

    2015-04-01

    In this study, the probability of pharmacokinetic/pharmacodynamic target attainment (PTA) of ceftaroline against clinical isolates causing community-acquired bacterial pneumonia (CABP) and complicated skin and skin-structure infection (cSSSI) in Europe was evaluated. Three dosing regimens were assessed: 600 mg every 12 h (q12 h) as a 1-h infusion (standard dose) or 600 mg every 8 h (q8 h) as a 2-h infusion in virtual patients with normal renal function; and 400 mg q12 h as a 1-h infusion in patients with moderate renal impairment. Pharmacokinetic and microbiological data were obtained from the literature. The PTA and the cumulative fraction of response (CFR) were calculated by Monte Carlo simulation. In patients with normal renal function, the ceftaroline standard dose (600 mg q12 h as a 1-h infusion) can be sufficient to treat CABP due to ceftazidime-susceptible (CAZ-S) Escherichia coli, CAZ-S Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (CFR>90%). However, against meticillin-resistant S. aureus (MRSA), the CFR was 72%. In cSSSI, the CFR was also <80% for MRSA. Administration of ceftaroline 600 mg q8 h as a 2-h infusion or 400 mg q12 h as a 1-h infusion in patients with moderate renal insufficiency provided a high probability of treatment success (CFR ca. 100%) for most micro-organisms causing CABP and cSSSI, including MRSA and penicillin-non-susceptible S. pneumoniae. These results suggest that in patients with normal renal function, ceftaroline 600 mg q8 h as a 2-h infusion may be a better option than the standard dose, especially if the MRSA rate is high. PMID:25700566

  18. Novel Carbapenem Antibiotics for Parenteral and Oral Applications: In Vitro and In Vivo Activities of 2-Aryl Carbapenems and Their Pharmacokinetics in Laboratory Animals

    PubMed Central

    Fujimoto, Koichi; Hatano, Kazuo; Nakai, Toru; Terashita, Shigeyuki; Matsumoto, Masahiro; Eriguchi, Yoshiro; Eguchi, Ken; Shimizudani, Takeshi; Sato, Kimihiko; Kanazawa, Katsunori; Sunagawa, Makoto; Ueda, Yutaka

    2013-01-01

    SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including β-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC90s of ≤1 μg/ml. Unlike tebipenem (MIC50, 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC50, ≥128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their in vitro activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae, have low selective pressure on antipseudomonal carbapenem

  19. Summary of Ceftaroline Activity against Pathogens in the United States, 2010: Report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Surveillance Program

    PubMed Central

    Sader, Helio S.; Farrell, David J.; Jones, Ronald N.

    2012-01-01

    The Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States, a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine census regions (5 to 10 medical centers per region). All organisms were isolated from documented infections, including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent β-lactam agent tested against staphylococci. The MIC90 values were 1 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA; 98.4% susceptible) and 0.5 μg/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureus and CoNS) were inhibited at ceftaroline MIC values of ≤2 μg/ml. Ceftaroline also displayed potent activity against streptococci (MIC90, 0.015 μg/ml for beta-hemolytic streptococci; MIC90, 0.25 μg/ml for penicillin-resistant Streptococcus pneumoniae). Potent activity was also shown against Gram-negative pathogens (Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Furthermore, wild-type strains of Enterobacteriaceae (non-extended-spectrum β-lactamase [ESBL]-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making

  20. Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections

    PubMed Central

    Gadsby, N.J.; McHugh, M.P.; Russell, C.D.; Mark, H.; Conway Morris, A.; Laurenson, I.F.; Hill, A.T.; Templeton, K.E.

    2015-01-01

    The frequent lack of a positive and timely microbiological diagnosis in patients with lower respiratory tract infection (LRTI) is an important obstacle to antimicrobial stewardship. Patients are typically prescribed broad-spectrum empirical antibiotics while microbiology results are awaited, but, because these are often slow, negative, or inconclusive, de-escalation to narrow-spectrum agents rarely occurs in clinical practice. The aim of this study was to develop and evaluate two multiplex real-time PCR assays for the sensitive detection and accurate quantification of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We found that all eight bacterial targets could be reliably quantified from sputum specimens down to a concentration of 100 CFUs/reaction (8333 CFUs/mL). Furthermore, all 249 positive control isolates were correctly detected with our assay, demonstrating effectiveness on both reference strains and local clinical isolates. The specificity was 98% on a panel of nearly 100 negative control isolates. Bacterial load was quantified accurately when three bacterial targets were present in mixtures of varying concentrations, mimicking likely clinical scenarios in LRTI. Concordance with culture was 100% for culture-positive sputum specimens, and 90% for bronchoalveolar lavage fluid specimens, and additional culture-negative bacterial infections were detected and quantified. In conclusion, a quantitative molecular test for eight key bacterial causes of LRTI has the potential to provide a more sensitive decision-making tool, closer to the time-point of patient admission than current standard methods. This should facilitate de-escalation from broad-spectrum to narrow-spectrum antibiotics, substantially improving patient management and supporting efforts to curtail inappropriate antibiotic use. PMID:25980353

  1. Ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia

    PubMed Central

    Mpenge, Mbiye A; MacGowan, Alasdair P

    2015-01-01

    Ceftaroline is a new parenteral cephalosporin approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft tissue infections (cSSTIs) including those due to methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has broad-spectrum activity against gram-positive and gram-negative bacteria and exerts its bactericidal effects by binding to penicillin-binding proteins (PBPs), resulting in inhibition of bacterial cell wall synthesis. It binds to PBP 2a of MRSA with high affinity and also binds to all six PBPs in Streptococcus pneumoniae. In in vitro studies, ceftaroline demonstrated potent activity against Staphylococcus aureus (including MRSA and vancomycin-intermediate isolates), Streptococcus pneumoniae (including multidrug resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, and many common gram-negative pathogens, excluding extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa. In Phase II and Phase III clinical trials, ceftaroline was noninferior to its comparator agents and demonstrated high clinical cure rates in the treatment of cSSTIs and CAP. It demonstrated favorable outcomes in patients treated for both regulatory-approved indications and unlicensed indications in a retrospective analysis. Ceftaroline is a safe and effective option for treatment in specific patient populations in which its efficacy and safety have been proven. This article reviews the challenges in the treatment of cSSTI and CAP, ceftaroline and its microbiology, pharmacology, efficacy, and safety data which support its use in treatment of cSSTIs and CAP. PMID:25897241

  2. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

    PubMed

    Hare, K M; Grimwood, K; Chang, A B; Chatfield, M D; Valery, P C; Leach, A J; Smith-Vaughan, H C; Morris, P S; Byrnes, C A; Torzillo, P J; Cheng, A C

    2015-11-01

    Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage. PMID

  3. [Analysis on the sensitivity to beta-lactam antibiotics of respiratory-infectious isolates on the second survey on the sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007--concerning the aspect of PK/PD break points].

    PubMed

    Niki, Yoshihito; Kohno, Shigeru; Watanabe, Akira; Aoki, Nobuki

    2009-06-01

    Sensitivity to beta-lactam antibiotics of isolates clinically obtained from respiratory infection sites in adults on the second survey on sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007 was investigated according to the classification of the "Guideline for treatment for adult nosocomial pneumonia in 2008". Among the primary antibacterial drugs for mild (A) and moderate (B) nosocomial pneumonia in adults, beta-lactam antibiotics; ceftriaxone (CTRX), sulbactam/ampicillin (SBT/ABPC), panipenem/betamipron (PAPM/BP), tazobactam/piperacillin (TAZ/PIPC), imipenem/cilastatin (IPM/CS), meropenem (MEPM), doripenem (DRPM), biapenem (BIPM) were studied to evaluate their clinical efficacy. The covering rate was analyzed using the minimal inhibitory concentration (MIC) and break point of pharmacokinetics/pharmacodynamics (PK/PD). Consequently, the results with methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae revealed the MIC90 of all antibacterial drugs to be at low levels, while almost 100% of isolates were within the range of PK/PD break points except BIPM and SBT/ABPC to H. influenzae, and SBT/ABPC to K. pneumoniae. However, the analysis of P. aeruginosa didn't reach 100% for the covering rates of isolates, indicating that these drugs did not have a complete inhibitory action to restrict bacterial proliferation. The analysis of all 5 carbapenem drugs showed superiority to TAZ/PIPC in MIC90 while covering rates of isolates at PK/PD break points showed inferiority to TAZ/PIPC. This tendency was found to be more significant in covering the rates of isolates on the regular dose with maximal bactericidal action and on the maximum dose. This is because the maximum dose approved in Japan is as low as half that in IPM/CS and 1/3 that in MEPM in Western countries. PMID:19882981

  4. [Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627) in children].

    PubMed

    Tajima, T; Niimi, R; Kobayashi, M; Kobayashi-Negishi, S; Kondo, Y; Nakayama-Esaki, E; Nishimura, S; Hagiwara, N; Abe, T

    1994-07-01

    The results are summarized as follows: 1. A total of 10 patients were treated with biapenem (L-627). We received informed consent from all of their parents. Each dose was 6 mg/kg, and it was administered 3 times daily (40 mg/kg, 4 times daily in meningitis), in a 30-minute intravenous drip infusion for 5-17 days. The clinical efficacies of L-627 in 10 patients with bacterial infections (1 with purulent meningitis, 1 with sepsis, 5 with pneumonia, 2 with urinary tract infection and 1 with purulent tonsillitis) were evaluated as excellent in 8 patients, as good in 2 patients with an efficacy rate of 100%. Seven causative organisms found in 5 patients (Streptococcus pneumoniae in 2, Moraxella (Branhamella) catarrhalis in 2, Haemophilus influenzae in 2 and Pseudomonas aeruginosa in 1) were eradicated. No adverse reaction was observed in any of the 10 patients. 2. Pharmacokinetic studies Peak plasma concentrations of L-627 were 12.5-13.7 micrograms/ml at the dose of 6 mg/kg administered by 30-minute drip infusion. Plasma half-lives of L-627 in the beta-phase averaged 0.72 hour (0.63-0.80 hour). CSF concentration/plasma concentration ratios of L-627 were 1.12/8.16 micrograms/ml (Day 2, 1.17 hours after at dose of 20 mg/kg), 0.88/3.44 micrograms/ml (Day 3, 4.0 hours after at dose of 30 mg/kg) and 0.68/5.12 micrograms/ml (Day 13, 3.0 hours after at dose of 40 mg/kg) administered by 30-minute drip infusion in the child with purulent meningitis (case 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7933524

  5. Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

    PubMed

    Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T

    2015-09-01

    The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia. PMID:26059041

  6. Contribution of Trimeric Autotransporter C-Terminal Domains of Oligomeric Coiled-Coil Adhesin (Oca) Family Members YadA, UspA1, EibA, and Hia to Translocation of the YadA Passenger Domain and Virulence of Yersinia enterocolitica▿

    PubMed Central

    Ackermann, Nikolaus; Tiller, Maximilian; Anding, Gisela; Roggenkamp, Andreas; Heesemann, Jürgen

    2008-01-01

    The Oca family is a novel class of autotransporter-adhesins with highest structural similarity in their C-terminal transmembrane region, which supposedly builds a beta-barrel pore in the outer membrane (OM). The prototype of the Oca family is YadA, an adhesin of Yersinia enterocolitica and Yersinia pseudotuberculosis. YadA forms a homotrimeric lollipop-like structure on the bacterial surface. The C-terminal regions of three YadA monomers form a barrel in the OM and translocate the trimeric N-terminal passenger domain, consisting of stalk, neck, and head region to the exterior. To elucidate the structural and functional role of the C-terminal translocator domain (TLD) and to assess its promiscuous capability with respect to transport of related passenger domains, we constructed chimeric YadA proteins, which consist of the N-terminal YadA passenger domain and C-terminal TLDs of Oca family members UspA1 (Moraxella catarrhalis), EibA (Escherichia coli), and Hia (Haemophilus influenzae). These constructs were expressed in Y. enterocolitica and compared for OM localization, surface exposure, oligomerization, adhesion properties, serum resistance, and mouse virulence. We demonstrate that all chimeric YadA proteins translocated the YadA passenger domain across the OM. Y. enterocolitica strains producing YadA chimeras or wild-type YadA showed comparable binding to collagen and epithelial cells. However, strains producing YadA chimeras were attenuated in serum resistance and mouse virulence. These results demonstrate for the first time that TLDs of Oca proteins of different origin are efficient translocators of the YadA passenger domain and that the cognate TLD of YadA is essential for bacterial survival in human serum and mouse virulence. PMID:18487327

  7. Synthesis and structure-activity relationship of amidine derivatives of 3,4-ethylenedioxythiophene as novel antibacterial agents.

    PubMed

    Stolić, Ivana; Čipčić Paljetak, Hana; Perić, Mihaela; Matijašić, Mario; Stepanić, Višnja; Verbanac, Donatella; Bajić, Miroslav

    2015-01-27

    Current antibacterial chemotherapeutics are facing an alarming increase in bacterial resistance pressuring the search for novel agents that would expand the available therapeutic arsenal against resistant bacterial pathogens. In line with these efforts, a series of 9 amidine derivatives of 3,4-ethylenedioxythiophene were synthesized and, together with 18 previously synthesized analogs, evaluated for their relative DNA binding affinity, in vitro antibacterial activities and preliminary in vitro safety profile. Encouraging antibacterial activity of several subclasses of tested amidine derivatives against Gram-positive (including resistant MRSA, MRSE, VRE strains) and Gram-negative bacterial strains was observed. The bis-phenyl derivatives were the most antibacterially active, while compound 19 from bis-benzimidazole class exhibited the widest spectrum of activity (with MIC of 4, 2, 0.5 and ≤0.25 μg/ml against laboratory strains of Staphyloccocus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, respectively and 4-32 μg/ml against clinical isolates of sensitive and resistant S. aureus, Staphylococcus epidermidis and Enterococcus faecium) and also demonstrated the strongest DNA binding affinity (ΔTm of 15.4 °C). Asymmetrically designed compounds and carboxamide-amidines were, in general, less active. Molecular docking indicated that the shape of the 3,4-ethylenedioxythiophene derivatives and their ability to form multiple electrostatic and hydrogen bonds with DNA, corresponds to the binding modes of other minor-groove binders. Herein reported results encourage further investigation of this class of compounds as novel antibacterial DNA binding agents. PMID:25461312

  8. Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

    PubMed

    Yanagihara, Katsunori; Kadota, Junichi; Aoki, Nobuki; Matsumoto, Tetsuya; Yoshida, Masaki; Yagisawa, Morimasa; Oguri, Toyoko; Sato, Junko; Ogasawara, Kazuhiko; Wakamura, Tomotaro; Sunakawa, Keisuke; Watanabe, Akira; Iwata, Satoshi; Kaku, Mitsuo; Hanaki, Hideaki; Ohsaki, Yoshinobu; Watari, Tomohisa; Toyoshima, Eri; Takeuchi, Kenichi; Shiokoshi, Mayumi; Takeda, Hiroaki; Miki, Makoto; Kumagai, Toshio; Nakanowatari, Susumu; Takahashi, Hiroshi; Utagawa, Mutsuko; Nishiya, Hajime; Kawakami, Sayoko; Kobayashi, Nobuyuki; Takasaki, Jin; Mezaki, Kazuhisa; Konosaki, Hisami; Aoki, Yasuko; Yamamoto, Yumiko; Shoji, Michi; Goto, Hajime; Saraya, Takeshi; Kurai, Daisuke; Okazaki, Mitsuhiro; Niki, Yoshihito; Yoshida, Koichiro; Kawana, Akihiko; Saionji, Katsu; Fujikura, Yuji; Miyazawa, Naoki; Kudo, Makoto; Sato, Yoshimi; Yamamoto, Masaki; Yoshida, Takashi; Nakamura, Masahiko; Tsukada, Hiroki; Imai, Yumiko; Tsukada, Ayami; Kawasaki, Satoshi; Honma, Yasuo; Yamamoto, Toshinobu; Ban, Nobuyoshi; Mikamo, Hiroshige; Sawamura, Haruki; Miyara, Takayuki; Toda, Hirofumi; Sato, Kaori; Nakamura, Tadahiro; Fujikawa, Yasunori; Mitsuno, Noriko; Mikasa, Keiichi; Kasahara, Kei; Sano, Reiko; Sugimoto, Keisuke; Asari, Seishi; Nishi, Isao; Toyokawa, Masahiro; Miyashita, Naoyuki; Koguchi, Yutaka; Kusano, Nobuchika; Mihara, Eiichirou; Kuwabara, Masao; Watanabe, Yaeko; Kawasaki, Yuji; Takeda, Kenichi; Tokuyasu, Hirokazu; Masui, Kayoko; Negayama, Kiyoshi; Hiramatsu, Kazufumi; Aoki, Yosuke; Fukuoka, Mami; Magarifuchi, Hiroki; Nagasawa, Zenzo; Suga, Moritaka; Muranaka, Hiroyuki; Morinaga, Yoshitomo; Honda, Junichi; Fujita, Masaki

    2015-06-01

    The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis. PMID:25817352

  9. Strategies developed by bacteria and virus for protection from the human complement system.

    PubMed

    Blom, A M

    2004-01-01

    The complement system is an important part of innate immunity providing immediate protection against pathogens without a need for previous exposure. Its importance is clearly shown by the fact that patients lacking complement components suffer from fulminant and recurring infections. Complement is an explosive cascade, and in order to control it there are inhibitors present on every human cell and also circulating in blood. However, many infectious agents have developed strategies to prevent clearance and destruction by complement. Some pathogens simply hijack the host's complement inhibitors, while others are able to produce their own homologues of human inhibitors. Knowledge of these mechanisms on a molecular level may aid development of vaccines and novel therapeutic strategies that would be more specific than the use of antibiotics that, apart from causing resistance problems, also affect the normal flora, the outcome of which could be devastating. In this study the structural requirements and functional consequences of interactions between the major soluble inhibitor of complement C4b-binding protein and Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes, Escherichia coli K1, Moraxella catarrhalis and Candida albicans are described. Furthermore, a novel inhibitor produced by Kaposi's sarcoma-associated herpesvirus is identified and characterized in detail: KCP. It is shown that KCP inhibits classical C3-convertase and presents activated complement factors C4b and C3b for destruction by a serine proteinase, factor I. Using molecular modelling and site-directed mutagenesis, it was possible to localize sites on the surface of KCP required for complement inhibition and it is concluded that KCP uses molecular mechanisms identical to human inhibitors. PMID:15276914

  10. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract

    PubMed Central

    Mgode, Georgies F.; Weetjens, Bart J.; Nawrath, Thorben; Cox, Christophe; Jubitana, Maureen; Machang'u, Robert S.; Cohen-Bacrie, Stéphan; Bedotto, Marielle; Drancourt, Michel; Schulz, Stefan

    2012-01-01

    Trained African giant-pouched rats (Cricetomys gambianus) can detect Mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis (TB). However, rats' ability to discriminate between clinical sputum containing other Mycobacterium spp. and nonmycobacterial species of the respiratory tract is unknown. It is also unknown whether nonmycobacterial species produce odor similar to M. tuberculosis and thereby cause the detection of smear-negative sputum. Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and rats. Mycobacterium spp. were isolated on Lowenstein-Jensen medium, and nonmycobacterial species were isolated on four different media. The odor from nonmycobacterial species from smear- and M. tuberculosis culture-negative sputa detected by ≥2 rats (“rat positive”) was analyzed by gas chromatography-mass spectrometry and compared to the M. tuberculosis odor. Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%) of 47 mycobacterial isolates were M. tuberculosis complex, with 75.7% from rat-positive sputa. Ten isolates were nontuberculous mycobacteria, one was M. intracellulare, one was M. avium subsp. hominissuis, and eight were unidentified. Rat-positive sputa with Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus spp., and Enterococcus spp. were associated with TB. Rhodococcus, Nocardia, Streptomyces, Staphylococcus, and Candida spp. from rat-positive sputa did not produce M. tuberculosis-specific volatiles (methyl nicotinate, methyl para-anisate, and ortho-phenylanisole). Prevalence of Mycobacterium-related Nocardia and Rhodococcus in smear-negative sputa did not equal that of smear-negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings and the absence of M. tuberculosis