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Sample records for avium complex mac

  1. GENETIC FINGERPRINTING OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS ISOLATED FROM HOSPITAL PATIENTS AND THE ENVIRONMENT

    EPA Science Inventory

    A particularly pathogenic group of mycobacteria belong to the Mycobacterium avium complex (MAC), which includes M. avium and M. intracellulare. MAC organisms cause disease in children, the elderly, and immuno-compromised individuals. A critical step in preventing MAC infections...

  2. GENETIC FINGERPRINTING OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS ISOLATED FROM HOSPITAL PATIENTS AND THE ENVIRONMENT

    EPA Science Inventory

    A particularly pathogenic group of mycobacteria belong to the Mycobacterium avium complex (MAC), which includes M. avium and M. intracellulare. MAC organisms cause disease in children, the elderly, and immuno-compromised individuals. A critical step in preventing MAC infections...

  3. Infection of Eurasian badgers (Meles meles) with Mycobacterium avium complex (MAC) bacteria.

    PubMed

    Balseiro, Ana; Merediz, Isabel; Sevilla, Iker A; García-Castro, Carmen; Gortázar, Christian; Prieto, José M; Delahay, Richard J

    2011-05-01

    There are few reports of infection with Mycobacterium avium complex (MAC) bacteria in badgers. In this study archive data relating to the isolation of MAC organisms from badgers in the UK is presented, and information derived from recent cases of such infection in Spain is used to illustrate the associated pathology and to characterise strain types. Tissue samples were cultured for mycobacteria and, in the case of Spanish badgers, were examined both histopathologically and using immunohistochemistry, and DNA typing of M. avium isolates was also carried out. A total of 5 (7.35%) and 281 (0.51%) isolates of M. avium spp. were recovered from badgers from the studies in Spain and the UK, respectively. DNA typing of the isolates from Spain identified the sub-species M. avium hominissuis and M. avium avium. These findings provide new information on the prevalence of MAC organisms in badgers in the UK and Spain. The extent to which infected badgers may be involved in the epidemiology of M. avium in other wild or domestic hosts remains unknown.

  4. Proposal to elevate Mycobacterium avium complex ITS sequevar MAC-Q to Mycobacterium vulneris sp. nov.

    PubMed

    van Ingen, J; Boeree, M J; Kösters, K; Wieland, A; Tortoli, E; Dekhuijzen, P N R; van Soolingen, D

    2009-09-01

    The Mycobacterium avium complex (MAC) consists of four recognized species, Mycobacterium avium, Mycobacterium colombiense, Mycobacterium intracellulare and Mycobacterium chimaera, and a variety of other strains that may be members of undescribed taxa. We report on two isolates of a scotochromogenic, slowly growing, non-tuberculous Mycobacterium species within the M. avium complex from a lymph node and an infected wound after a dogbite of separate patients in The Netherlands. The extrapulmonary infections in immunocompetent patients suggested a high level of virulence. These isolates were characterized by a unique nucleotide sequence in the 16S rRNA gene, 99% similar to Mycobacterium colombiense, and the MAC-Q 16S-23S internal transcribed spacer (ITS) sequence. Sequence analyses of the hsp65 gene revealed 97% similarity to M. avium. The rpoB gene sequence was 98% similar to M. colombiense. Phenotypically, the scotochromogenicity, positive semi-quantitative catalase and heat-stable catalase tests, negative tellurite reductase and urease tests and susceptibility to hydroxylamine and oleic acid set these isolates apart from related species. High-performance liquid chromatography analysis of cell-wall mycolic acid content revealed a unique pattern, related to that of M. avium and M. colombiense. Together, these findings supported a separate species status within the Mycobacterium avium complex. We propose elevation of scotochromogenic M. avium complex strains sharing this 16S gene and MAC-Q ITS sequence to separate species status, for which the name Mycobacterium vulneris sp. nov. is proposed. The type strain is NLA000700772T (=DSM 45247T=CIP 109859T).

  5. Investigation of Mycobacterium avium complex (MAC) in Australian commercial milk using qPCR.

    PubMed

    Adhikari, Shraddha; Caro Tohme, Tanya; Whiley, Harriet

    2017-02-01

    This technical research communication describes the first study to use quantitative polymerase chain reaction (qPCR) to investigate the presence of Mycobacterium avium complex (MAC) in Australian pasteurised milk. MAC is the most common NTM responsible for human illnesses and includes M. avium subspecies paratuberculosis (MAP). MAC is a causative agent of lymphadenitis in children, with contaminated food and water considered as a likely source. As such the presence of MAC in milk would have public health significance. MAP has been linked to Crohn's disease and is also the causative agent of Johne's disease in cattle. Previous studies have detected MAP in pasteurised milk from Brazil, India, Czech Republic, USA, Argentina, UK, Iran, Ireland and the United Kingdom. This study investigated a total of 180 commercially available Australian pasteurised milk samples which were tested for MAC DNA in triplicate using PCR. All samples were negative for MAC DNA. An additional 14 milk samples were tested, incubated for 3 weeks at 37 °C to potentially increase the concentration of any viable MAC that may be present and then retested. All samples were again negative for MAC DNA. This could be due to concentrations below the limit of detection, limited sample size or could be reflective of the Australian biosecurity control protocols and surveillance of Johne's disease in ruminant animals.

  6. Zoonotic aspects of Mycobacterium bovis and Mycobacterium avium-intracellulare complex (MAC).

    PubMed

    Biet, Franck; Boschiroli, Maria Laura; Thorel, Marie Françoise; Guilloteau, Laurence A

    2005-01-01

    Pathogens that are transmitted between the environment, wildlife, livestock and humans represent major challenges for the protection of human and domestic animal health, the economic sustainability of agriculture, and the conservation of wildlife. Among such pathogens, the genus Mycobacterium is well represented by M. bovis, the etiological agent of bovine tuberculosis, M. avium ssp. paratuberculosis (Map) the etiological agent of Johne disease, M. avium ssp. avium (Maa) and in a few common cases by other emergent environmental mycobacteria. Epidemiologic surveys performed in Europe, North America and New Zealand have demonstrated the existence and importance of environmental and wildlife reservoirs of mycobacterial infections that limit the attempts of disease control programmes. The aim of this review is to examine the zoonotic aspects of mycobacteria transmitted from the environment and wildlife. This work is focused on the species of two main groups of mycobacteria classified as important pathogens for humans and animals: first, M. bovis, the causative agent of bovine tuberculosis, which belongs to the M. tuberculosis complex and has a broad host range including wildlife, captive wildlife, domestic livestock, non-human primates and humans; the second group examined, is the M. avium-intracellulare complex (MAC) which includes M. avium ssp. avium causing major health problems in AIDS patients and M. avium ssp. paratuberculosis the etiological agent of Johne disease in cattle and identified in patients with Crohn disease. MAC agents, in addition to a broad host range, are environmental mycobacteria found in numerous biotopes including the soil, water, aerosols, protozoa, deep litter and fresh tropical vegetation. This review examines the possible reservoirs of these pathogens in the environment and in wildlife, their role as sources of infection in humans and animals and their health impact on humans. The possibilities of control and management programmes for

  7. Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower.

    PubMed

    Whiley, Harriet; Giglio, Steven; Bentham, Richard

    2015-07-24

    Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the "unhooking" showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation.

  8. Assessing the effectiveness of low-pressure ultraviolet light for inactivating Mycobacterium avium complex (MAC) micro-organisms

    EPA Science Inventory

    Aims: To assess low-pressure ultraviolet light (LP-UV) inactivation kinetics of Mycobacterium avium complex (MAC) strains in a water matrix using collimated beam apparatus. Methods and Results: Strains of M. avium (n = 3) and Mycobacterium intracellulare (n = 2) were exposed t...

  9. Assessing the effectiveness of low-pressure ultraviolet light for inactivating Mycobacterium avium complex (MAC) micro-organisms

    EPA Science Inventory

    Aims: To assess low-pressure ultraviolet light (LP-UV) inactivation kinetics of Mycobacterium avium complex (MAC) strains in a water matrix using collimated beam apparatus. Methods and Results: Strains of M. avium (n = 3) and Mycobacterium intracellulare (n = 2) were exposed t...

  10. Characteristics of Mycobacterium avium complex (MAC) pulmonary disease in previously treated lung cancer patients.

    PubMed

    Meier, Erin; Pennington, Kelly; Gallo de Moraes, Alice; Escalante, Patricio

    2017-01-01

    Mycobacterium avium complex (MAC) is responsible for a large portion of non-tuberculous mycobacterial (NTM) infections worldwide. Host factors such as active malignancy, immunosuppression, chronic obstructive pulmonary disease (COPD) and bronchiectasis increase the risk of MAC infection. However, the relationship between previously treated lung cancer with subsequent development of MAC pulmonary disease and treatment outcomes have not been previously studied. We retrospectively identified all patients with lung cancer and MAC pulmonary disease documented in medical records at Mayo Clinic between January 2005 and October 2016. Patients who were diagnosed with MAC pulmonary disease before or at the time of lung cancer diagnosis were excluded. Patients meeting all inclusion criteria underwent chart review for prior oncologic treatments, clinical characteristics, and MAC treatment response. We identified 13 patients with MAC pulmonary disease and prior lung cancer, including 4 men and 9 women. Eight patients had structural lung disease that can predispose to MAC pulmonary disease, including bronchiectasis (23.0%) and COPD (46.2%). Four (30.8%) had no apparent immunosuppression or other risk factor(s) for MAC pulmonary disease. Primary pulmonary malignancies included pulmonary carcinoid, adenocarcinoma, and squamous cell carcinoma. Ten (76.9%) patients were started on antimicrobial treatment for MAC, and 8 (61.5%) patients completed MAC treatment with 6 (46.1%) patients achieving symptomatic improvement. MAC pulmonary disease in previously treated lung cancer can occur without apparent risk factors for this NTM infection. Symptomatic improvement with MAC antimicrobial therapy appears to be lower than expected but comorbidities might influence outcomes in this patient population.

  11. THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

    EPA Science Inventory

    Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

  12. THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

    EPA Science Inventory

    Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

  13. The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

    PubMed

    Fordham von Reyn, C; Arbeit, R D; Tosteson, A N; Ristola, M A; Barber, T W; Waddell, R; Sox, C H; Brindle, R J; Gilks, C F; Ranki, A; Bartholomew, C; Edwards, J; Falkinham, J O; O'Connor, G T

    1996-08-01

    To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. Prospective cohort study. University hospitals and outpatient AIDS programs. HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

  14. THE EFFECT OF TEMPERATURE ON THE GROWTH OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS

    EPA Science Inventory

    MAC organisms are able to grow, persist, and colonize in water distribution systems and may amplify in hospital hot water systems. This study examined the response of MAC organisms (M. avium, M. intracellulare, and MX) to a range of temperatures commonly associated with drinking...

  15. THE EFFECT OF TEMPERATURE ON THE GROWTH OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS

    EPA Science Inventory

    MAC organisms are able to grow, persist, and colonize in water distribution systems and may amplify in hospital hot water systems. This study examined the response of MAC organisms (M. avium, M. intracellulare, and MX) to a range of temperatures commonly associated with drinking...

  16. Genetic relatedness of Mycobacterium avium-intracellulare complex isolates from patients with pulmonary MAC disease and their residential soils.

    PubMed

    Fujita, K; Ito, Y; Hirai, T; Maekawa, K; Imai, S; Tatsumi, S; Niimi, A; Iinuma, Y; Ichiyama, S; Mishima, M

    2013-06-01

    Mycobacterium avium-intracellulare complex (MAC) strains were recovered from 48.9% of residential soil samples (agricultural farms (n = 7), residential yards (n = 79), and planting pots (n = 49)) of 100 pulmonary MAC patients and 35 non-infected control patients. The frequency of MAC recovery did not differ among soil types or among patients regardless of the presence of pulmonary MAC disease, infecting MAC species or period of soil exposure. Variable numbers of tandem repeats (VNTR) analysis for MAC clinical and soil isolates revealed 78 different patterns in 47 M. avium clinical isolates and 41 soil isolates, and 53 different patterns in 18 M. intracellulare clinical isolates and 37 soil isolates. Six clinical and corresponding soil isolate pairs with an identical VNTR genotype were from case patients with high soil exposure (≥2 h per week, 37.5% (6/16) with high exposure compared with 0.0% (0/19) with low or no exposure, p <0.01), suggesting that residential soils are a likely source of pulmonary MAC infection. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  17. Mycobacterium avium complex (MAC) Immune Reconstitution Syndrome (IRIS) With Reduced Susceptibility to Ethambutol in an HIV-Infected Patient.

    PubMed

    Adams, Immaculata B; Schafer, Jason J; Roberts, Amity L; Short, William R

    2014-09-01

    To describe a case of Mycobacterium avium complex (MAC) lymphadenitis complicated by immune reconstitution syndrome (IRIS) and reduced susceptibility to ethambutol. A 24-year-old man was diagnosed in October 2012 with advanced HIV infection upon hospitalization for multiple opportunistic infections (OIs). Within 5 months of starting antiretroviral therapy, the patient developed significant cervical lymphadenopathy concerning for MAC/IRIS. Acid-fast bacilli were detected in the primary lymph node biopsy smear, and culture results confirmed the presence of MAC. Susceptibility testing revealed an organism susceptible to azithromycin, with an elevated minimum inhibitory concentration (MIC) to ethambutol (8 µg/mL). Currently, there is no interpretation for an ethambutol MIC of 8 µg/mL for MAC. A review of the primary literature revealed the possibility of decreased ethambutol susceptibility when the MIC is above 1 µg/mL, and therefore, therapy was replaced by rifabutin in combination with azithromycin. Current guidelines recommend a 2-drug regimen for the treatment of MAC, specifically a macrolide plus ethambutol. Guidelines also emphasize MAC susceptibility testing for macrolides only. Susceptibility results from this patient's biopsy prompted an evaluation of the effectiveness of his antimycobacterial regimen. Reduced ethambutol susceptibility in this patient triggered a search of the primary literature that resulted in the decision to replace ethambutol with rifabutin. Additional clinical trials are needed to define susceptibility breakpoints for ethambutol and other antimycobacterial agents used for MAC infection treatment and to direct clinical decisions when elevated MICs to primary agents are identified. © The Author(s) 2014.

  18. Mycobacterium colombiense sp. nov., a novel member of the Mycobacterium avium complex and description of MAC-X as a new ITS genetic variant.

    PubMed

    Murcia, Martha I; Tortoli, Enrico; Menendez, M Carmen; Palenque, Elia; Garcia, Maria J

    2006-09-01

    Forty-five mycobacterial strains isolated from 23 Colombian HIV-positive patients were identified as members of the Mycobacterium avium complex (MAC) and were characterized using different molecular approaches. Seven of the isolates showed characteristic features that allowed them to be differentiated from other members of the complex. The isolates had a novel 16S-23S rRNA internal transcribed spacer (ITS 1) gene sequence which is described as a new sequevar, MAC-X. All of the seven novel isolates gave a positive result with the MAC-specific AccuProbe (Gen-Probe), but tested negative for Mycobacterium avium and Mycobacterium intracellulare species-specific probes (64 and 100 % of the isolates, respectively). The novel isolates could be differentiated phenotypically from other members of the MAC on the basis of the production of urease and by a consistent mycolic acid pattern. The novel isolates shared some characteristics with M. avium, such as the avium variant I (av-I) pattern of the hsp65 gene as determined by PCR restriction analysis and a positive PCR result for the mig (macrophage-induced) gene. However, the novel isolates showed a unique 16S rRNA gene sequence. DNA-DNA relatedness values, from 24 to 44 %, confirmed the distinction of the novel isolates from other members of the MAC at the genetic level and their status as members of a separate species. The novel isolates are proposed as representatives of a novel species, Mycobacterium colombiense sp. nov., that is closely related to M. avium within the MAC. The type strain is 10B(T) (=CIP 108962(T)=CECT 3035(T)).

  19. The Mycobacterium avium complex.

    PubMed Central

    Inderlied, C B; Kemper, C A; Bermudez, L E

    1993-01-01

    Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing

  20. Characterization of the virulence of Mycobacterium avium complex (MAC) isolates in mice.

    PubMed Central

    Pedrosa, J; Flórido, M; Kunze, Z M; Castro, A G; Portaels, F; McFadden, J; Silva, M T; Appelberg, R

    1994-01-01

    The virulence of different isolates of MAC was studied in naturally susceptible BALB/c mice. In preliminary experiments, MAC bacteria forming smooth transparent colonies on solid media (SmT variants) were found to be virulent for BALB/c mice, causing progressive infection; smooth opaque (SmOp) were generally avirulent, being slowly eliminated from the infected organs; and rough (Rg) variants were either avirulent or as virulent as SmT variants. We chose to compare the virulence of different isolates of MAC of different origins, studying only the SmT morphotype. Strains of MAC isolated from naturally infected animals were those that most consistently caused progressive infections. AIDS patients-derived isolates were of intermediate virulence or devoid of virulence in mice. The environmental strains were eliminated from mice or did not proliferate. Strains of MAC isolated from individuals who were not infected by HIV varied in virulence from completely avirulent to highly virulent. There was no close correlation between virulence and restriction fragment length polymorphism (RFLP) type, although all highly virulent strains were of the A/I type. There was also no correlation between virulence analysed in vivo and the ability to grow in cultured macrophages. Images Fig. 1 PMID:7955524

  1. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov.

    PubMed

    Tortoli, Enrico; Rindi, Laura; Garcia, Maria J; Chiaradonna, Patrizia; Dei, Rosanna; Garzelli, Carlo; Kroppenstedt, Reiner M; Lari, Nicoletta; Mattei, Romano; Mariottini, Alessandro; Mazzarelli, Gianna; Murcia, Martha I; Nanetti, Anna; Piccoli, Paola; Scarparo, Claudio

    2004-07-01

    The possibility that the strains included within the Mycobacterium avium complex (MAC), but not belonging either to M. avium or to Mycobacterium intracellulare, may be members of undescribed taxa, has already been questioned by several taxonomists. A very homogeneous cluster of 12 strains characterized by identical nucleotide sequences both in the 16S rDNA and in the 16S-23S internal transcribed spacer was investigated. Similar strains, previously reported in the literature, had been assigned either to the species M. intracellulare on the basis of the 16S rDNA similarity or to the group of MAC intermediates. However, several phenotypical and epidemiological characteristics seem to distinguish these strains from all other MAC organisms. The unique mycolic acid pattern obtained by HPLC is striking as it is characterized by two clusters of peaks, instead of the three presented by all other MAC organisms. All of the strains have been isolated from humans and all but one came from the respiratory tract of elderly people. The clinical significance of these strains, ascertained for seven patients, seems to suggest an unusually high virulence. The characteristics of all the strains reported in the literature, genotypically identical to the ones described here, seem to confirm our data, without reports of isolations from animals or the environment or, among humans, from AIDS patients. Therefore, an elevation of the MAC variant was proposed and characterized here, with the name Mycobacterium chimaera sp. nov.; this increases the number of species included in the M. avium complex. The type strain is FI-01069T (=CIP 107892T=DSM 44623T).

  2. Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease.

    PubMed

    Matsumura, Yoko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Yasui, Satsuki; Mochida, Naoko; Nakano, Ryuichi; Kasahara, Kei; Tomoda, Koichi; Yano, Hisakazu; Kayano, Shin-Ichi; Ito, Toshihiro

    2017-01-01

    Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

  3. Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease

    PubMed Central

    Matsumura, Yoko; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Yasui, Satsuki; Mochida, Naoko; Nakano, Ryuichi; Kasahara, Kei; Tomoda, Koichi; Yano, Hisakazu; Kayano, Shin-ichi

    2017-01-01

    Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection. PMID:28827842

  4. Detection of Legionella, L. pneumophila and Mycobacterium Avium Complex (MAC) along Potable Water Distribution Pipelines

    PubMed Central

    Whiley, Harriet; Keegan, Alexandra; Fallowfield, Howard; Bentham, Richard

    2014-01-01

    Inhalation of potable water presents a potential route of exposure to opportunistic pathogens and hence warrants significant public health concern. This study used qPCR to detect opportunistic pathogens Legionella spp., L. pneumophila and MAC at multiple points along two potable water distribution pipelines. One used chlorine disinfection and the other chloramine disinfection. Samples were collected four times over the year to provide seasonal variation and the chlorine or chloramine residual was measured during collection. Legionella spp., L. pneumophila and MAC were detected in both distribution systems throughout the year and were all detected at a maximum concentration of 103 copies/mL in the chlorine disinfected system and 106, 103 and 104 copies/mL respectively in the chloramine disinfected system. The concentrations of these opportunistic pathogens were primarily controlled throughout the distribution network through the maintenance of disinfection residuals. At a dead-end and when the disinfection residual was not maintained significant (p < 0.05) increases in concentration were observed when compared to the concentration measured closest to the processing plant in the same pipeline and sampling period. Total coliforms were not present in any water sample collected. This study demonstrates the ability of Legionella spp., L. pneumophila and MAC to survive the potable water disinfection process and highlights the need for greater measures to control these organisms along the distribution pipeline and at point of use. PMID:25046636

  5. Detection of Legionella, L. pneumophila and Mycobacterium avium complex (MAC) along potable water distribution pipelines.

    PubMed

    Whiley, Harriet; Keegan, Alexandra; Fallowfield, Howard; Bentham, Richard

    2014-07-18

    Inhalation of potable water presents a potential route of exposure to opportunistic pathogens and hence warrants significant public health concern. This study used qPCR to detect opportunistic pathogens Legionella spp., L. pneumophila and MAC at multiple points along two potable water distribution pipelines. One used chlorine disinfection and the other chloramine disinfection. Samples were collected four times over the year to provide seasonal variation and the chlorine or chloramine residual was measured during collection. Legionella spp., L. pneumophila and MAC were detected in both distribution systems throughout the year and were all detected at a maximum concentration of 103 copies/mL in the chlorine disinfected system and 106, 103 and 104 copies/mL respectively in the chloramine disinfected system. The concentrations of these opportunistic pathogens were primarily controlled throughout the distribution network through the maintenance of disinfection residuals. At a dead-end and when the disinfection residual was not maintained significant (p < 0.05) increases in concentration were observed when compared to the concentration measured closest to the processing plant in the same pipeline and sampling period. Total coliforms were not present in any water sample collected. This study demonstrates the ability of Legionella spp., L. pneumophila and MAC to survive the potable water disinfection process and highlights the need for greater measures to control these organisms along the distribution pipeline and at point of use.

  6. Mycobacterium Avium Complex (MAC)

    MedlinePlus

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  7. Human health risks for Legionella and Mycobacterium avium complex (MAC) from potable and non-potable uses of roof-harvested rainwater.

    PubMed

    Hamilton, Kerry A; Ahmed, Warish; Toze, Simon; Haas, Charles N

    2017-08-01

    A quantitative microbial risk assessment (QMRA) of opportunistic pathogens Legionella pneumophila (LP) and Mycobacterium avium complex (MAC) was undertaken for various uses of roof-harvested rainwater (RHRW) reported in Queensland, Australia to identify appropriate usages and guide risk management practices. Risks from inhalation of aerosols due to showering, swimming in pools topped up with RHRW, use of a garden hose, car washing, and toilet flushing with RHRW were considered for LP while both ingestion (drinking, produce consumption, and accidental ingestion from various activities) and inhalation risks were considered for MAC. The drinking water route of exposure presented the greatest risks due to cervical lymphadenitis and disseminated infection health endpoints for children and immune-compromised populations, respectively. It is therefore not recommended that these populations consume untreated rainwater. LP risks were up to 6 orders of magnitude higher than MAC risks for the inhalation route of exposure for all scenarios. Both inhalation and ingestion QMRA simulations support that while drinking, showering, and garden hosing with RHRW may present the highest risks, car washing and clothes washing could constitute appropriate uses of RHRW for all populations, and toilet flushing and consumption of lettuce irrigation with RHRW would be appropriate for non- immune-compromised populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms were measured. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1s-1, and the EPMs of fifteen environmental isolates ranged from -1...

  9. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms isolated from clinical and environmental sources were measured in 9.15 mM KH2PO4 buffered water. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1 ...

  10. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms were measured. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1s-1, and the EPMs of fifteen environmental isolates ranged from -1...

  11. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms isolated from clinical and environmental sources were measured in 9.15 mM KH2PO4 buffered water. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1 ...

  12. Genotyping of Mycobacterium avium complex organisms using multispacer sequence typing.

    PubMed

    Cayrou, Caroline; Turenne, Christine; Behr, Marcel A; Drancourt, Michel

    2010-03-01

    Mycobacterium avium complex (MAC) currently comprises eight species of environmental and animal-associated, slowly-growing mycobacteria: Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense , Mycobacterium bouchedurhonense, Mycobacterium marseillense and Mycobacterium timonense. In humans, MAC organisms are responsible for opportunistic infections whose unique epidemiology remains poorly understood, in part due to the lack of a genotyping method applicable to all eight MAC species. In this study we developed multispacer sequence typing (MST), a sequencing-based method, for the genotyping of MAC organisms. An alignment of the genome sequence of M. avium subsp. hominissuis strain 104 and M. avium subsp. paratuberculosis strain K-10 revealed 621 intergenic spacers <1000 bp. From these, 16 spacers were selected that ranged from 300 to 800 bp and contained a number of variable bases, <50 within each of the 16 spacers. Four spacers were successfully PCR-amplified and sequenced in 11 reference strains. Combining the sequence of these four spacers in 106 MAC organisms, including 83 M. avium, 11 M. intracellulare , six M. chimaera, two M. colombiense and one each of M. arosiense, M. bouchedurhonense, M. marseillense and M. timonense, yielded a total of 45 spacer types, with an index of discrimination of 0.94. Each spacer type was specific for a species and certain spacer types were specific for subspecies of M. avium. MST is a new method for genotyping of organisms belonging to any one of the eight MAC species tested in this study.

  13. REAL-TIME QUANTITATIVE PCR DETECTION OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS IN DRINKING WATER

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U.S. Environmental Protection Agency's Contaminant Candidate List (CCL) due to their association with human disease and occurrence in public drinkin...

  14. Detection of quantification of Mycobacterium avium complex organisms in drinking water

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U. S. Environmental Protection Agency’s Contaminant Candidate List 2 (CCL2) due to their association with human disease and occurrence in public dr...

  15. Detection of quantification of Mycobacterium avium complex organisms in drinking water

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U. S. Environmental Protection Agency’s Contaminant Candidate List 2 (CCL2) due to their association with human disease and occurrence in public dr...

  16. REAL-TIME QUANTITATIVE PCR DETECTION OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS IN DRINKING WATER

    EPA Science Inventory

    The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and others. MAC are listed on the U.S. Environmental Protection Agency's Contaminant Candidate List (CCL) due to their association with human disease and occurrence in public drinkin...

  17. AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM AVIUM COMPLEX ISOLATES RECOVERED FROM SOUTHERN CALIFORNIA

    EPA Science Inventory

    Fine-scale genotyping methods are necessary in order to identify possible sources of human exposure to opportunistic pathogens belonging to the Mycobacterium avium complex (MAC). In this study, amplified fragment length polymorphism (AFLP) analysis was evaluated for fingerprintin...

  18. AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM AVIUM COMPLEX ISOLATES RECOVERED FROM SOUTHERN CALIFORNIA

    EPA Science Inventory

    Fine-scale genotyping methods are necessary in order to identify possible sources of human exposure to opportunistic pathogens belonging to the Mycobacterium avium complex (MAC). In this study, amplified fragment length polymorphism (AFLP) analysis was evaluated for fingerprintin...

  19. Efficient Differentiation of Mycobacterium avium Complex Species and Subspecies by Use of Five-Target Multiplex PCR▿

    PubMed Central

    Shin, Sung Jae; Lee, Byung Soo; Koh, Won-Jung; Manning, Elizabeth J. B.; Anklam, Kelly; Sreevatsan, Srinand; Lambrecht, Randall S.; Collins, Michael T.

    2010-01-01

    Infections caused by the Mycobacterium avium complex (MAC) are on the rise in both human and veterinary medicine. A means of effectively discriminating among closely related yet pathogenetically diverse members of the MAC would enable better diagnosis and treatment as well as further our understanding of the epidemiology of these pathogens. In this study, a five-target multiplex PCR designed to discriminate MAC organisms isolated from liquid culture media was developed. This MAC multiplex was designed to amplify a 16S rRNA gene target common to all Mycobacterium species, a chromosomal target called DT1 that is unique to M. avium subsp. avium serotypes 2 and 3, to M. avium subsp. silvaticum, and to M. intracellulare, and three insertion sequences, IS900, IS901, and IS1311. The pattern of amplification results allowed determination of whether isolates were mycobacteria, whether they were members of the MAC, and whether they belonged to one of three major MAC subspecies, M. avium subsp. paratuberculosis, M. avium subsp. avium, and M. avium subsp. hominissuis. Analytical sensitivity was 10 fg of M. avium subsp. paratuberculosis genomic DNA, 5 to 10 fg of M. avium subsp. avium genomic DNA, and 2 to 5 fg of DNA from other mycobacterial species. Identification accuracy of the MAC multiplex was evaluated by testing 53 bacterial reference strains consisting of 28 different mycobacterial species and 12 nonmycobacterial species. Identification accuracy in a clinical setting was evaluated for 223 clinical MAC isolates independently identified by other methods. Isolate identification agreement between the MAC multiplex and these comparison assays was 100%. The novel MAC multiplex is a rapid, reliable, and simple assay for discrimination of MAC species and subspecies in liquid culture media. PMID:20810779

  20. In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium avium Complex.

    PubMed

    Brown-Elliott, Barbara A; Philley, Julie V; Griffith, David E; Thakkar, Foram; Wallace, Richard J

    2017-02-01

    We performed bedaquiline broth microdilution susceptibility testing using Clinical and Laboratory Standards Institute (CLSI) guidelines on 103 respiratory isolates of Mycobacterium avium complex (MAC), including multidrug-resistant isolates. Approximately 90% of isolates had bedaquiline MICs of ≤0.008 μg/ml, and 102/103 isolates had MICs of ≤0.015 μg/ml. Bedaquiline has excellent potential for use in patients with MAC infections, although for reasons of its metabolism by the cytochrome P450 system, it should not be given with rifampin.

  1. Species identification of Mycobacterium avium complex isolates by a variety of molecular techniques.

    PubMed

    Beggs, M L; Stevanova, R; Eisenach, K D

    2000-02-01

    Organisms in the Mycobacterium avium complex (MAC; M. avium, M. intracellulare, and "nonspecific or X" MAC) are emerging pathogens among individual organisms of which significant genetic variability is displayed. The objective of the present study was to evaluate various molecular methods for the rapid and definitive identification of MAC species. Isolates were obtained from both human immunodeficiency virus (HIV)-positive patients and HIV-negative patients with and without known predisposing conditions. The isolates were initially hybridized with nucleic acid probes complementary to the rRNA of the respective mycobacterial species (AccuProbe Culture Confirmation kits for M. avium, M. intracellulare, and MAC species; Gen-Probe). Isolates were also examined by PCR and in some cases by Southern blot hybridization for the insertion element IS1245. Two other techniques included a PCR assay that amplifies the mig gene, a putative virulence factor for MAC, and hsp65 gene amplification and sequencing. This study led to the following observations. Eighty-five percent of the isolates from HIV-positive patients were M. avium and 86% of the isolates from HIV-negative patients were M. intracellulare. Fifteen of the M. avium isolates did not contain IS1245 and 7% of the M. intracellulare isolates were found to carry IS1245. All of the M. avium strains were mig positive, and all of the M. intracellulare strains were mig negative.

  2. Multilocus enzyme electrophoresis analysis of the Mycobacterium avium complex and other mycobacteria.

    PubMed Central

    Wasem, C F; McCarthy, C M; Murray, L W

    1991-01-01

    Multilocus enzyme electrophoresis analysis was used to evaluate the Mycobacterium avium complex (MAC), M. paratuberculosis, and nine other mycobacterial species. The average number of alleles per locus was 2.8 for the 35 MAC and 2 M. paratuberculosis strains which represented 24 electrophoretic types (ETs) and two distinct groups. The M. avium group was resolved into 17 ETs and contained the M. paratuberculosis ET. The M. intracellulare group consisted of six ETs. There was complete agreement between Gen-Probe identification and group placement by multilocus enzyme electrophoresis. The mean genetic diversity per locus for the 24 MAC ETs was 0.38. This procedure subdivided some serovars and, if implemented, should prove to be a powerful epidemiologic tool for the MAC. Eleven additional ETs were formed after the data for the other mycobacterial species were pooled with those for the MAC. PMID:2007633

  3. Mycobacterium avium complex in day care hot water systems, and persistence of live cells and DNA in hot water pipes.

    PubMed

    Bukh, Annette S; Roslev, Peter

    2014-04-01

    The Mycobacterium avium complex (MAC) is a group of opportunistic human pathogens that may thrive in engineered water systems. MAC has been shown to occur in drinking water supplies based on surface water, but less is known about the occurrence and persistence of live cells and DNA in public hot water systems based on groundwater. In this study, we examined the occurrence of MAC in hot water systems of public day care centers and determined the persistence of live and dead M. avium cells and naked DNA in model systems with the modern plumbing material cross-linked polyethylene (PEX). The occurrence of MAC and co-occurrence of Legionella spp. and Legionella pneumophila were determined using cultivation and qPCR. Co-occurrences of MAC and Legionella were detected in water and/or biofilms in all hot water systems at temperatures between 40 and 54 °C. Moderate correlations were observed between abundance of culturable MAC and that of MAC genome copies, and between MAC and total eubacterial genome copies. No quantitative relationship was observed between occurrence of Legionella and that of MAC. Persistence in hot water of live and dead M. avium cells and naked DNA was studied using PEX laboratory model systems at 44 °C. Naked DNA and DNA in dead M. avium cells persisted for weeks. Live M. avium increased tenfold in water and biofilms on PEX. The results suggest that water and biofilms in groundwater-based hot water systems can constitute reservoirs of MAC, and that amplifiable naked DNA is relatively short-lived, whereas PEX plumbing material supports persistence and proliferation of M. avium.

  4. [Distribution of PRA patterns of clinical isolates of the Mycobacterium avium complex from Spain and South America].

    PubMed

    Murcia, Martha Isabel; Leao, Sylvia Cardoso; Ritacco, Viviana; Palenque, Elia; de Oliveira, Rosangela Siqueira; Reniero, Ana; Menendez, Maria Carmen; Telles, María Alice da Silva; Hadad, David Jamil; Barrera, Lucía; García, María Jesús

    2004-06-01

    Mycobacterium avium complex (MAC) infections are the most frequent systemic infections associated with advanced AIDS. DNA probes for accurate identification of mycobacteria are available but are very expensive in many Latin American settings. Consequently, most Latin American diagnostic laboratories employ inaccurate and outdated tests for mycobacteria identification. Therefore, PCR restriction analysis (PRA) of the hsp65 gene was evaluated for the identification of 163 MAC human isolates originated from Spain and South America. The predominant PRA type in each country was: M. avium type I in Argentina (23/42, 55%) and Brazil (48/72, 67%), M. avium type II in Spain (18/26, 69%) and M. avium type III in Colombia (10/23, 43%). The Colombia frequency is noteworthy, since the PRA type III was quite infrequent in the other three countries. Furthermore, its presence has not been reported outside the Americas. The advantages and disadvantages of PRA in diagnostic mycobacteriology are discussed.

  5. Mycobacterium avium Complex Osteomyelitis in Persons With Human Immunodeficiency Virus: Case Series and Literature Review

    PubMed Central

    Wood, Brian R.; Buitrago, Martha O.; Patel, Sugat; Hachey, David H.; Haneuse, Sebastien; Harrington, Robert D.

    2015-01-01

    In persons with advanced immunosuppression, Mycobacterium avium complex (MAC) typically causes disseminated disease with systemic symptoms. We report 2 cases in which MAC caused localized osteomyelitis in human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy with rising CD4 counts. We summarize 17 additional cases of HIV-associated MAC osteomyelitis from the literature and compare CD4 count at presentation for vertebral cases versus nonvertebral cases, which reveals a significantly higher CD4 at presentation for vertebral cases (median 251 cells/µL vs 50 cells/µL; P = .043; Mann–Whitney U test). The literature review demonstrates that the majority of cases of MAC osteomyelitis, especially vertebral, occurs in individuals with CD4 counts that have increased to above 100 cells/µL on antiretroviral therapy. Among HIV-infected individuals with osteomyelitis, MAC should be considered a possible etiology, particularly in the setting of immune reconstitution. PMID:26180837

  6. Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

    PubMed Central

    Kim, Woo Sik; Kim, Jong-Seok; Kim, Hong Min; Kwon, Kee Woong; Cho, Sang-Nae; Shin, Sung Jae; Koh, Won-Jung

    2015-01-01

    The latency and reactivation of Mycobacterium tuberculosis infection has been well studied. However, there have been few studies of the latency and reactivation of Mycobacterium avium complex (MAC), the most common etiological non-tuberculous Mycobacterium species next to M. tuberculosis in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of M. avium and M. intracellulare. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in M. avium infection) or sulfasalazine (four out of six mice in both M. avium and M. intracellulare infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection. PMID:26406237

  7. Mycobacterium avium complex organisms predominantly colonize in the bathtub inlets of patients' bathrooms.

    PubMed

    Nishiuchi, Yukiko; Tamura, Aki; Kitada, Seigo; Taguri, Takahiro; Matsumoto, Sohkichi; Tateishi, Yoshitaka; Yoshimura, Mamiko; Ozeki, Yuriko; Matsumura, Narumi; Ogura, Hisashi; Maekura, Ryoji

    2009-05-01

    Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.

  8. rpoB sequence-based identification of Mycobacterium avium complex species.

    PubMed

    Ben Salah, Iskandar; Adékambi, Toidi; Raoult, Didier; Drancourt, Michel

    2008-12-01

    The Mycobacterium avium complex (MAC) comprises slowly growing mycobacteria responsible for opportunistic infections and zoonoses. The ability to speciate MAC isolates in the clinical microbiology laboratory is critical for determining the organism implicated in clinical disease and for epidemiological investigation of the source of infection. Investigation of a 711 bp variable fragment of rpoB flanked by the Myco-F/Myco-R primers found a 0.7-5.1 % divergence among MAC reference strains, with Mycobacterium chimaera and Mycobacterium intracellulare being the most closely related. Using a 0.7 % divergence cut-off, 83 % of 100 clinical isolates, which had been previously identified by phenotypic characteristics and 16S-23S rDNA intergenic spacer (ITS) probing, were identified as M. avium, 8 % as M. intracellulare and 2 % as M. chimaera. The uniqueness of seven isolates, exhibiting < 99.3 % rpoB sequence similarity with MAC reference strains, was confirmed by 16S rDNA, ITS and hsp65 sequencing and phylogenetic analyses. Partial rpoB gene sequencing using the Myco-F/Myco-R primers permits one-step identification of MAC isolates at the species level and the detection of potentially novel MAC species.

  9. Mycobacterium avium complex suppurative parotitis in a patient with human immunodeficiency virus infection presenting with immune reconstitution inflammatory syndrome.

    PubMed

    Babiker, Zahir Osman Eltahir; Beeston, Christine; Purcell, Janet; Desai, Niranjan; Ustianowski, Andrew

    2010-11-01

    Restoration of the immune system following initiation of antiretroviral therapy can result in an adverse phenomenon known as immune reconstitution inflammatory syndrome (IRIS). Herein, we report a case of Mycobacterium avium complex (MAC) suppurative parotitis associated with IRIS in a patient with advanced human immunodeficiency virus disease. To the best of our knowledge, this is the first reported case of MAC parotitis in the setting of IRIS and clinicians should be aware of this condition.

  10. Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases

    PubMed Central

    Deshpande, Devyani; Srivastava, Shashikant; Musuka, Sandirai

    2016-01-01

    Mycobacterium avium-intracellulare complex (MAC) causes an intractable intracellular infection that presents as chronic pulmonary disease. Currently, therapy consists of ethambutol and macrolides and takes several years to complete. The neuroleptic phenothiazine thioridazine kills mycobacteria by inhibiting the electron transport chain. In several experiments with bacterial populations of up to 1012 CFU/ml, we failed to isolate any bacteria resistant to 3 times the MIC of thioridazine, suggesting the absence of resistant mutants at bacterial burdens severalfold higher than those encountered in patients. In the hollow-fiber model of intracellular MAC (HFS-MAC), thioridazine achieved an extracellular half-life of 16.8 h and an intracellular half-life of 19.7 h. Thioridazine concentrations were >28,000-fold higher inside infected macrophages than in the HFS-MAC central compartment (equivalent to plasma). Thioridazine maximal kill was 5.20 ± 0.75 log10 CFU/ml on day 7 (r2 = 0.96) and 7.19 ± 0.31 log10 CFU/ml on day 14 (r2 = 0.99), the highest seen with any drug in the system. Dose fractionation studies revealed that thioridazine efficacy and acquired drug resistance were driven by the peak concentation-to-MIC ratio, with a 50% effective concentration (EC50) of 2.78 ± 0.44 for microbial killing. Acquired drug resistance was encountered by day 21 with suboptimal doses, demonstrating that fluctuating drug concentrations drive evolution faster than static concentrations in mutation frequency studies. However, the thioridazine EC50 changed 16.14-fold when the concentration of fetal bovine serum was changed from 0% to 50%, suggesting that intracellular potency could be heavily curtailed by protein binding. Efficacy in patients will depend on the balance between trapping of the drug in the pulmonary system and the massive intracellular concentrations versus very high protein binding of thioridazine. PMID:27216055

  11. Lessons from Mycobacterium avium complex-associated pneumonitis: a case report

    PubMed Central

    Zota, Victor; Angelis, Sheryn M; Fraire, Armando E; McNamee, Ciaran; Kielbasa, Shasta; Libraty, Daniel H

    2008-01-01

    Introduction Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. Case presentation We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-α, a pro-inflammatory cytokine. Conclusion The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms. PMID:18477401

  12. Lessons from Mycobacterium avium complex-associated pneumonitis: a case report.

    PubMed

    Zota, Victor; Angelis, Sheryn M; Fraire, Armando E; McNamee, Ciaran; Kielbasa, Shasta; Libraty, Daniel H

    2008-05-13

    Mycobacterium avium complex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection. We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+ T-cells and CD68+ histiocytes. The granulomas were strongly positive for tumor necrosis factor-alpha, a pro-inflammatory cytokine. The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms.

  13. [Measurement of sitafloxacin MIC for Mycobacterium avium complex and application for treatment of pulmonary nontuberculous mycobacteriosis].

    PubMed

    Fujita, Masaki; Matsumoto, Takemasa; Hirano, Ryousuke; Harada, Eiji; Ikegame, Satoshi; Nakanishi, Yoichi; Watanabe, Kentaro

    2014-12-01

    Treatment for pulmonary nontuberculous mycobacteriosis is difficult. Since current treatment has limitation, new application is needed. Fluoroquinolone is one of candidates. We have investigated the feasibility of sitafloxacin (STFX). At first, the drug of MIC (minimum inhibitory concentration) was determined by the methods based on BrothMIC NTM. The MICs of STFX, moxifloxacin (MFLX), gatifloxacin (GFLX) were low. On contrast, the MICs of garenoxacin (GRNX) and tosufloxacin (TFLX) were high. Two cases of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease were treated by STFX-contained regimen. In all cases of pulmonary MAC disease, improve of symptoms and chest CT images were attained. Adverse events were slight. These MIC studies and case reports suggest that STFX might have excellent in vitro and in vivo antimicrobial activities against MAC and is considered to be a candidate for the medication against pulmonary MAC disease.

  14. Mycobacterium avium complex--the role of potable water in disease transmission.

    PubMed

    Whiley, H; Keegan, A; Giglio, S; Bentham, R

    2012-08-01

    Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major public health concern. It is responsible for a wide spectrum of disease dependent on subspecies, route of infection and patients pre-existing conditions. Presently, there is limited research on the incidence of MAC infection that considers both pulmonary and other clinical manifestations. MAC has been isolated from various terrestrial and aquatic environments including natural waters, engineered water systems and soils. Identifying the specific environmental sources responsible for human infection is essential in minimizing disease prevalence. This paper reviews current literature and case studies regarding the wide spectrum of disease caused by MAC and the role of potable water in disease transmission. Potable water was recognized as a putative pathway for MAC infection. Contaminated potable water sources associated with human infection included warm water distribution systems, showers, faucets, household drinking water, swimming pools and hot tub spas. MAC can maintain long-term contamination of potable water sources through its high resistance to disinfectants, association with biofilms and intracellular parasitism of free-living protozoa. Further research is required to investigate the efficiency of water treatment processes against MAC and into construction and maintenance of warm water distribution systems and the role they play in MAC proliferation. No claim to Australian Government works Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  15. Association between polyclonal and mixed mycobacterial Mycobacterium avium complex infection and environmental exposure.

    PubMed

    Fujita, Kohei; Ito, Yutaka; Hirai, Toyohiro; Kubo, Takeshi; Maekawa, Koichi; Togashi, Kaori; Ichiyama, Satoshi; Mishima, Michiaki

    2014-01-01

    Polyclonal and mixed mycobacterial Mycobacterium avium complex (MAC) infection is observed in pulmonary MAC disease. Human living environments contain multiple species or genotypes of nontuberculous mycobacterial strains and are considered sources of infection. To investigate the association of environmental exposure with polyclonal and mixed mycobacterial infection in pulmonary MAC disease after adjustments for potential confounding diseases and conditions and radiographic findings. We collected two separate sputum samples from 102 patients and single sputum samples from 18 patients in whom the second MAC strain was not isolated in our prospective cohort of pulmonary MAC disease. MAC isolates from sputum samples and patients' residential soils were used for variable number of tandem repeats (VNTR) analyses. Polyclonal and mixed mycobacterial MAC infections were defined as having different VNTR genotypes and other mycobacterial species, respectively. Monoclonal MAC infection was defined as all isolates showing a single VNTR genotype. Associations of the type of infection with clinical and radiographic findings and environmental exposure were measured. Polyclonal and mixed mycobacterial MAC and monoclonal infections were observed in 42 and 78 patients, respectively. By stepwise regression analysis, patients with polyclonal and mixed mycobacterial MAC infections were associated with history of asthma (odds ratio [OR], 11.56; 95% confidence interval [CI], 1.41-255.77; P = 0.021), high soil exposure (≥2 h/wk; OR, 4.31; 95% CI, 1.72-11.45; P < 0.01), shower use in a bathroom (OR, 4.57; 95% CI, 1.28-23.23; P = 0.018), and swimming in a pool (OR, 9.69; 95% CI, 1.21-206.92; P < 0.01). Environmental exposure was associated with polyclonal and mixed mycobacterial MAC infection in pulmonary MAC disease.

  16. Relationship Between Lung Cancer and Mycobacterium Avium Complex Isolated Using Bronchoscopy

    PubMed Central

    Tamura, Atsuhisa; Hebisawa, Akira; Kusaka, Kei; Hirose, Takashi; Suzuki, Junko; Yamane, Akira; Nagai, Hideaki; Fukami, Takeshi; Ohta, Ken; Takahashi, Fumiaki

    2016-01-01

    Introduction: The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. Materials and Methods: The medical records of 1382 untreated lung cancer patients between 2003 and 2011 were collected using our hospital database. Of them, records for 1258 that had undergone bronchoscopy together with sampling for mycobacterial culture were reviewed. Patient characteristics were compared between those with MAC-positive/other nontuberculous mycobacteria (NTM)-negative bronchial washings and those with MAC-negative/other NTM-negative bronchial washings. Patients with MAC-positive lung cancer were cross-sectionally divided into MACLD and non-MACLD groups, and their features were assessed. Follow-up data for patients with lung cancer but without MACLD were reviewed for subsequent development of MACLD. Results: Of the 1258 patients with lung cancer, 25 (2.0%) had MAC-positive/other NTM-negative bronchial washings. The proportion of women (52% vs 30%; P = 0.0274) and patient age (72 years vs 69 years; P = 0.0380) were significantly higher in the MAC-positive/other NTM-negative lung cancer group (n = 25) than in the MAC-negative/other NTM-negative lung cancer group (n = 1223). There were 10 patients with lung cancer and MACLD and 15 without MACLD; significant differences in patient characteristics were not found between the two groups, and none of the 15 patients without MACLD subsequently developed MACLD. Conclusion: MAC culture-positive bronchial washing is positively associated with lung cancer. Female sex and advanced age, but not lung cancer characteristics, were found to be associated with MAC infection in patients with lung cancer. PMID:27335625

  17. Comparative in vivo activities of rifabutin and rifapentine against Mycobacterium avium complex.

    PubMed Central

    Klemens, S P; Grossi, M A; Cynamon, M H

    1994-01-01

    The dose-response activity of rifabutin and the comparative activities of rifabutin and rifapentine were evaluated in the beige mouse model of disseminated Mycobacterium avium complex (MAC) infection. In the dose-response study, mice were infected intravenously with approximately 10(7) viable M. avium ATCC 49601. Treatment with rifabutin at 10, 20, or 40 mg/kg of body weight was started 7 days postinfection and was administered daily for 10 days. The mice were sacrificed 3 to 5 days after the last dose. Spleens, livers, and lungs were homogenized, and viable cell counts were determined by serial dilution and plating onto Middlebrook 7H10 agar. A dose-related reduction in MAC cell counts in the organs was noted for this MAC isolate. The comparative activities of rifabutin and rifapentine were determined against a total of five MAC isolates in the beige mouse model. Rifabutin or rifapentine (20 mg/kg each) was administered to infected mice for 10 days. Groups of treated mice were compared with untreated control animals. Despite favorable in vitro susceptibility results, rifabutin and rifapentine had activities in the spleens against only two of the five MAC isolates. For these two MAC isolates, rifabutin was more active than rifapentine. These agents had activities in the lungs against three of five isolates. Further study of rifabutin or rifapentine against a broader range of clinical isolates in a murine infection model may be useful as part of the continuing development of newer rifamycins as anti-MAC agents. PMID:8192449

  18. [Strategies for Mycobacterium avium complex infection control in Japan: how do they improve the present situation?].

    PubMed

    Ogawa, Kenji; Sano, Chiaki

    2013-03-01

    Mycobacterium avium complex (MAC) were the most frequently isolated (about 80%) and most common cause of lung nontuberculosis. Its rate of infection is globally increasing, especially in Japan. In this situation, it is urgently needed to provide scientific evidences and develop therapeutic interventions in MAC infections. Recently, more and more patients are elderly women with no history of smoking, and they have reticulonodular infiltrates and patchy bilateral bronchiectasis. However the prognostic and intractable factors of MAC infections are poorly known. In this symposium, we address five novel strategies for MAC infection, concerning the more accurate incidence and prevalence rates compared with other countries, host defense associated with Th1/Th17 balance, route of MAC infection related soil exposure, MAC IgA antibody as a diagnosis maker, and improved chemotherapy including aminoglycoside or new quinolone. Appropriate clinical intervention may help to reduce the prolongation of MAC infection or enhance the activity of chemotherapy for the improved control of MAC. Below are the abstracts for each of the five speakers. 1. Review of current epidemiological study of pulmonary nontuberculous mycobacterial disease in Japan and the rest of the world: Kozo MORIMOTO (Respiratory Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association) The studies on pulmonary nontuberculous mycobacterial (NTM) disease prevalence were started in early 1970s in Japan by the Mycobacteriosis Research Group of National Chest Hospitals. They were followed by a questionnaire survey in 1990s, by the National Tuberculosis and NTM Survey in late 1990s, and recently by the questionnaire surveys conducted by the NTM Disease Research Committee. The latest data in Japan (from 2007) indicated a morbidity rate of 5.7 per 100,000 population. Deaths from NTM disease were reported for the first time in 1970 and showed a marked, steady increase until 2007, with 912 deaths in that year. We

  19. Serodiagnosis of Mycobacterium avium complex disease in humans: translational research from basic mycobacteriology to clinical medicine.

    PubMed

    Kobayashi, Kazuo

    2014-01-01

    Rapid and accurate diagnosis of infectious diseases, including mycobacterial disease such as tuberculosis (TB) and diseases due to nontuberculous mycobacteria (NTM), is a very important element of global health. The gold standard in diagnosis of mycobacterial diseases remains clinical examination, combined with direct microscopic examination of sputum and culture of bacteria. Culture of slowly growing mycobacteria, including Mycobacterium tuberculosis and NTM (such as M. avium complex: MAC), can take up to 4 to 6 weeks, and in 10-20% of cases the bacillus is not successfully cultivated. Diagnosis of MAC pulmonary disease (MAC-PD) is complicated and time-consuming (usually at least 1 month). I have characterized the nature of MAC antigens and immune responses from the aspect of basic mycobacteriology, and then translated to clinical science. My multicenter study in Japan has demonstrated the usefulness of a serodiagnostic test to determine serum IgA antibodies against mycobacterial glycopeptidolipid (GPL) core antigen for diagnosing MAC-PD within a few hours. To validate in a larger number of patients, at diverse geographic locations, and among other races, the test was also assessed the usefulness internationally in the United States and Taiwan. In this review, I discuss development of serodiagnosis of MAC-PD by translational research and international collaboration study.

  20. Isolation of Mycobacterium avium complex from bone marrow aspirates of AIDS patients in Brazil.

    PubMed

    Barreto, J A; Palaci, M; Ferrazoli, L; Martins, M C; Suleiman, J; Lorenço, R; Ferreira, O C; Riley, L W; Johnson, W D; Galvão, P A

    1993-09-01

    Mycobacterium avium complex (MAC) infection has not been reported as a major opportunistic infection among patients with AIDS in Latin America or Africa. In this study, 125 AIDS patients who had persistent fever, anemia, and leukopenia were examined among 2628 AIDS patients admitted to Instituto de Infectologia Emilio Ribas between May 1990 and April 1992. From the bone marrow aspirates of the 125 patients, MAC was isolated from 23 (18.4%) and Mycobacterium tuberculosis was isolated from 9 (7.2%). Between 1985 and 1990, only 11 MAC isolations among 60,000 cultures obtained from human immunodeficiency virus-seronegative patients were documented in São Paulo. Hence, the minimal estimated rate of MAC infection in AIDS patients in this city was 23/2628, or 0.88%. These findings suggest that MAC infection is an important opportunistic infection, especially among a subset of patients with AIDS in Brazil who have clinical characteristics and risk activities similar to those associated with MAC infections in North America and Europe.

  1. [A case of environmental infection with pulmonary Mycobacterium avium complex disease from a residential bathroom of a patient suggested by variable-number tandem-repeat typing of Mycobacterium avium tandem repeat loci].

    PubMed

    Taga, Shu; Niimi, Masaki; Kurokawa, Kazuhiro; Nakagawa, Taku; Ogawa, Kenji

    2012-05-01

    A 63-year-old woman was referred to our hospital because of bilateral infiltrations and nodular opacities in her chest radiograph taken in the mass radiography screening in September 2010. The chest computed tomography showed patchy infiltrations with bronchiectasis in the lower lung fields on both sides. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) disease based on the bacteria recovered from the sputum and the bronchoalveolar lavage fluid. To elucidate an environmental MAC source, we investigated her home, and isolated M. avium and M. gordonae from the bathtub and shower tap, respectively, in her residential bathroom. Analysis of the hsp65-PRA variants digested with BamHI and some insertion sequences showed that the clinical strains recovered from sputum and strains from the bathtub were M. avium subsp. hominissuis. A dendrogram of the Mycobacterium avium tandem repeat loci variable-number tandem-repeat (MATR-VNTR) analysis of the MAC strains showed that the bathtub strains formed a polyclonal colonization, and that 1 of the 5 MATR-VNTR patterns was identical to the corresponding pattern of the sputum strain from the patient. In conclusion, we believe that the residential bathroom of the patient was the environmental source of her pulmonary MAC disease, as has been previously reported.

  2. Infection Sources of a Common Non-tuberculous Mycobacterial Pathogen, Mycobacterium avium Complex

    PubMed Central

    Nishiuchi, Yukiko; Iwamoto, Tomotada; Maruyama, Fumito

    2017-01-01

    Numerous studies have revealed a continuous increase in the worldwide incidence and prevalence of non-tuberculous mycobacteria (NTM) diseases, especially pulmonary Mycobacterium avium complex (MAC) diseases. Although it is not clear why NTM diseases have been increasing, one possibility is an increase of mycobacterial infection sources in the environment. Thus, in this review, we focused on the infection sources of pathogenic NTM, especially MAC. The environmental niches for MAC include water, soil, and dust. The formation of aerosols containing NTM arising from shower water, soil, and pool water implies that these niches can be infection sources. Furthermore, genotyping has shown that clinical isolates are identical to environmental ones from household tap water, bathrooms, potting soil, and garden soil. Therefore, to prevent and treat MAC diseases, it is essential to identify the infection sources for these organisms, because patients with these diseases often suffer from reinfections and recurrent infections with them. In the environmental sources, MAC and other NTM organisms can form biofilms, survive within amoebae, and exist in a free-living state. Mycobacterial communities are also likely to occur in these infection sources in households. Water distribution systems are a transmission route from natural water reservoirs to household tap water. Other infection sources include areas with frequent human contact, such as soil and bathrooms, indicating that individuals may carry NTM organisms that concomitantly attach to their household belongings. To explore the mechanisms associated with the global spread of infection and MAC transmission routes, an epidemiological population-wide genotyping survey would be very useful. A good example of the power of genotyping comes from M. avium subsp. hominissuis, where close genetic relatedness was found between isolates of it from European patients and pigs in Japan and Europe, implying global transmission of this bacterium

  3. Infection Sources of a Common Non-tuberculous Mycobacterial Pathogen, Mycobacterium avium Complex.

    PubMed

    Nishiuchi, Yukiko; Iwamoto, Tomotada; Maruyama, Fumito

    2017-01-01

    Numerous studies have revealed a continuous increase in the worldwide incidence and prevalence of non-tuberculous mycobacteria (NTM) diseases, especially pulmonary Mycobacterium avium complex (MAC) diseases. Although it is not clear why NTM diseases have been increasing, one possibility is an increase of mycobacterial infection sources in the environment. Thus, in this review, we focused on the infection sources of pathogenic NTM, especially MAC. The environmental niches for MAC include water, soil, and dust. The formation of aerosols containing NTM arising from shower water, soil, and pool water implies that these niches can be infection sources. Furthermore, genotyping has shown that clinical isolates are identical to environmental ones from household tap water, bathrooms, potting soil, and garden soil. Therefore, to prevent and treat MAC diseases, it is essential to identify the infection sources for these organisms, because patients with these diseases often suffer from reinfections and recurrent infections with them. In the environmental sources, MAC and other NTM organisms can form biofilms, survive within amoebae, and exist in a free-living state. Mycobacterial communities are also likely to occur in these infection sources in households. Water distribution systems are a transmission route from natural water reservoirs to household tap water. Other infection sources include areas with frequent human contact, such as soil and bathrooms, indicating that individuals may carry NTM organisms that concomitantly attach to their household belongings. To explore the mechanisms associated with the global spread of infection and MAC transmission routes, an epidemiological population-wide genotyping survey would be very useful. A good example of the power of genotyping comes from M. avium subsp. hominissuis, where close genetic relatedness was found between isolates of it from European patients and pigs in Japan and Europe, implying global transmission of this bacterium

  4. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease.

    PubMed

    Wallace, Richard J; Iakhiaeva, Elena; Williams, Myra D; Brown-Elliott, Barbara A; Vasireddy, Sruthi; Vasireddy, Ravikiran; Lande, Leah; Peterson, Donald D; Sawicki, Janet; Kwait, Rebecca; Tichenor, Wellington S; Turenne, Christine; Falkinham, Joseph O

    2013-06-01

    Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.

  5. Absence of Mycobacterium intracellulare and Presence of Mycobacterium chimaera in Household Water and Biofilm Samples of Patients in the United States with Mycobacterium avium Complex Respiratory Disease

    PubMed Central

    Iakhiaeva, Elena; Williams, Myra D.; Brown-Elliott, Barbara A.; Vasireddy, Sruthi; Vasireddy, Ravikiran; Lande, Leah; Peterson, Donald D.; Sawicki, Janet; Kwait, Rebecca; Tichenor, Wellington S.; Turenne, Christine; Falkinham, Joseph O.

    2013-01-01

    Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC. PMID:23536397

  6. Late-Onset Disseminated Mycobacterium avium intracellulare Complex Infection (MAC), Cerebral Toxoplasmosis and Salmonella Sepsis in a German Caucasian Patient with Unusual Anti-Interferon-Gamma IgG1 Autoantibodies.

    PubMed

    Hanitsch, Leif G; Löbel, Madlen; Müller-Redetzky, Holger; Schürmann, Mariana; Suttorp, Norbert; Unterwalder, Nadine; Mönnich, Ulrike; Meisel, Christian; Wittke, Kirsten; Volk, Hans-Dieter; Scheibenbogen, Carmen; Kölsch, Uwe

    2015-05-01

    Since we described for the first time a patient with IgG4 autoantibodies to IFN-γ more than 10 years ago, many patients with IFN-γ IgG4 autoantibodies have been described, mostly in Mongolian/ Asian patients with a particular HLA background and in association with disseminated nontuberculous mycobacterial infections. Very recently, the first Caucasian US patient was reported and we now present the case of a 65-year old Caucasian woman with severe disseminated Mycobacterium avium infection, cerebral toxoplasmosis and salmonella sepsis who was tested positive for IFN-γ deficiency due to unusual anti-IFN-γ IgG1 autoantibodies. IFN-γ production after ex vivo ConA stimulation of the patient's whole blood and isolated peripheral blood mononuclear cells was assessed. Anti-human IFN-γ antibodies were measured by Ig/Ig-subclass-specific ELISA. In vitro physiologic relevance and blocking capacity of IFN-γ-stimulation by patient's serum was analysed by flow cytometric assessment of cytokine-induced phosphorylation of pSTAT1(Y701). Severely impaired IFN-γ production in the patient's whole blood but normal production in peripheral blood mononuclear cells in the absence of autologous serum was observed. High titre anti-IFN-γ antibodies of the IgG1 subclass could be demonstrated in the patient's serum by ELISA. Further, the addition of patient's serum to IFN-γ-stimulated immune cells showed inhibition of STAT1 phosphorylation. IFN-γ autoantibodies of any IgG-isotype should be considered in patients with severe opportunistic infections independent of age at onset and ethnicity.

  7. Rapid susceptibility testing of Mycobacterium avium complex and Mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1994-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of HIV infection will continue to rise more rapidly worldwide than predicted earlier. The AIDS patients are susceptible to diseases called opportunistic infections of which tuberculosis and Mycobacterium avium complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, MD, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. We proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis.

  8. DRESS syndrome presenting after initiation of mycobacterium avium complex osteomyelitis treatment.

    PubMed

    Blair, Paul W; Herrin, Douglas; Abaalkhail, Nawaf; Fiser, Wesley

    2015-10-05

    Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is characterised by fever, rash, eosinophilia and organ damage that develops 2-6 weeks after the initiation of a medication. We report a case of DRESS syndrome in a 79-year-old man that developed after the introduction of rifabutin, ethambutol and clarithromycin used to treat Mycobacterium avium complex (MAC) vertebral osteomyelitis. This case highlights treatment and management challenges in a patient with known MAC vertebral osteomyelitis requiring prolonged steroids. Steroids are the mainstays of treatment for moderate to severe cases of DRESS syndrome. Initiation of steroids for the treatment of DRESS syndrome among patients with concomitant infections requires multidisciplinary collaboration for optimal management. 2015 BMJ Publishing Group Ltd.

  9. Genetic relatedness among Mycobacterium paratuberculosis and M. avium complex.

    PubMed

    Labidi, A; Thoen, C O

    1989-01-01

    Total DNA was extracted from M. paratuberculosis (ATCC 19698) and from M. avium complex (ATCC 25291) cultivated on RVB-10 enriched liquid media. Restriction endonuclease analysis of total DNA was performed with 34 enzymes and DNA digestion profiles were compared. Fifteen enzymes revealed important differences between the two species. Two pairs of enzymes (EcoRII, BstNI) and (MboI, Sau3AI) provide evidence for the presence of dcmI and dam methylation in DNA of M. avium complex and M. paratuberculosis. The differences in DNA fragments of these two species could be of potential value in differentiating these clinically significant mycobacteria.

  10. Sequencing of hsp65 Distinguishes among Subsets of the Mycobacterium avium Complex

    PubMed Central

    Turenne, Christine Y.; Semret, Makeda; Cousins, Debby V.; Collins, Desmond M.; Behr, Marcel A.

    2006-01-01

    The Mycobacterium avium complex consists of epidemiologically distinct subsets. The classification of these subsets is complicated by a number of factors, including the ambiguous results obtained with phenotypic and genetic assays and the recent appreciation that human and avian strains appear to be distinct. In previous work, sequencing based on a 441-bp portion of the hsp65 gene has proven to efficiently classify isolates within the Mycobacterium genus but provides low resolution for distinguishing among members of the M. avium complex. Therefore, in this study, we have targeted the more variable 3′ region of the hsp65 gene to determine whether it can effectively discriminate M. avium complex isolates at the levels of species and subspecies. Primers designed for this target consistently generated amplicons for all organisms classified as M. avium complex. Sequences obtained indicate that M. intracellulare is genetically divergent from M. avium organisms, and distinct sequevars were obtained for M. avium subsets, including M. avium subsp. avium (bird type), M. avium subsp. hominissuis, and M. avium subsp. paratuberculosis. In addition, sequence differences served to distinguish bovine from ovine strains of M. avium subsp. paratuberculosis. A unique profile for M. avium subsp. silvaticum was not obtained. These results indicate that sequencing the 3′ region of the hsp65 gene can simply and unambiguously distinguish species and subspecies of the M. avium complex. PMID:16455896

  11. Broncho-Pleural Fistula with Hydropneumothorax at CT: Diagnostic Implications in Mycobacterium avium Complex Lung Disease with Pleural Involvement

    PubMed Central

    Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Kim, Jung Soo; Park, Hye Yun

    2016-01-01

    Objective To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. Materials and Methods We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. Results The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410–100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. Conclusion In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion. PMID:26957917

  12. Mycobacterium avium Complex Cervical Lymphadenitis in an Immunocompetent Adult▿

    PubMed Central

    Christensen, Joshua B.; Koeppe, John

    2010-01-01

    Nontuberculosis mycobacterial cervical lymphadenitis is a relatively common disease in immunocompetent children but a rare disease in immunocompetent adults. We report the diagnosis and treatment of Mycobacterium avium complex cervical lymphadenitis in an adult female. Our evaluation of immune competence, including gamma interferon (IFN-γ) and interleukin-12 (IL-12) signaling, found no evidence of deficiency. PMID:20668140

  13. Evaluation of the MycoAKT latex agglutination test for rapid diagnosis of Mycobacterium avium complex infections.

    PubMed

    Olano, J P; Holmes, H; Woods, G L

    1998-01-01

    Rapid diagnosis of Mycobacterium avium complex (MAC) bacteremia is important for management of patients with the acquired immunodeficiency syndrome who have disseminated MAC. The purpose of this study was to determine the reliability of the MycoAKT latex agglutination test for direct detection of MAC in positive mycobacterial blood cultures. First, colonies of isolates of previously identified mycobacteria, including 35 MAC, were tested. Of the 55 isolates evaluated, 33 were identified as MAC by the latex test, including 31 of the known MAC and 2 M. chelonae (sensitivity, 88.6%; specificity, 90.0%). Second, broth from 20 ESP II and 20 BACTEC 12B bottles seeded with isolates of MAC were tested. Aliquots from 19 (95%) ESP II cultures and 16 (80%) 12B cultures were positive by the latex test. In phase 3, broth from 115 signal-positive ESP II blood cultures were tested by latex agglutination. Forty-three subcultures from these bottles grew mycobacteria (41 MAC and 2 Mycobacterium tuberculosis complex); the remainder grew no organisms. Broth from 40 of the blood cultures (39 that grew MAC and 1 from which no organisms were recovered) were latex positive; thus, the sensitivity, specificity, and positive and negative predictive values of the latex test for direct identification of MAC in ESP II blood cultures were 95.1, 98.6, 97.5, and 97.3%, respectively. The mean time to detection of MAC was 14.6 days (range, 6-34 days) with the direct latex test, compared with 18.3 days (range, 9-36 days) with subculture and probe (p < 0.05).

  14. Hemolysin as a Virulence Factor for Systemic Infection with Isolates of Mycobacterium avium Complex

    PubMed Central

    Maslow, Joel N.; Dawson, David; Carlin, Elizabeth A.; Holland, Steven M.

    1999-01-01

    Isolates of the Mycobacterium avium complex were examined for hemolysin expression. Only invasive isolates of M. avium were observed to be hemolytic (P < 0.001), with activity the greatest for isolates of serovars 4 and 8. Thus, M. avium hemolysin appears to represent a virulence factor necessary for invasive disease. PMID:9889239

  15. Treatment of intracellular Mycobacterium avium complex infection by free and liposome-encapsulated sparfloxacin.

    PubMed Central

    Düzgüneş, N; Flasher, D; Reddy, M V; Luna-Herrera, J; Gangadharam, P R

    1996-01-01

    Mycobacterium avium-M. intracellulare complex (MAC) is the most frequent cause of opportunistic bacterial infection in patients with AIDS. Previous studies have indicated that liposome-encapsulated aminoglycosides are highly effective in treating MAC infections in mice. We investigated whether the fluoroquinolone sparfloxacin is effective in treating MAC infection in the murine macrophage-like cell line J774. Sparfloxacin was encapsulated in the membrane phase of multilamellar liposomes composed of phosphatidylglycerol-phosphatidylcholine-cholesterol (1:1:1 molar ratio). MAC-infected macrophages were treated for either 24 h or 4 days with free or liposome-encapsulated sparfloxacin. Treatment with free or liposome-encapsulated sparfloxacin (6 micrograms/ml) for 24 h resulted in the reduction of the growth index to 25 and 30% of that of untreated controls, respectively. When cultures were treated for 4 days, free sparfloxacin reduced the growth index to 6% of that of the untreated control, while liposome-encapsulated sparfloxacin reduced it to 8% of that of the control. PMID:8913475

  16. Attenuation of lymphocyte immune responses during Mycobacterium avium complex-induced lung disease due to increasing expression of programmed death-1 on lymphocytes

    PubMed Central

    Shu, Chin-Chung; Wang, Jann-Yuan; Wu, Ming-Fang; Wu, Chen-Tu; Lai, Hsin-Chih; Lee, Li-Na; Chiang, Bor-Luen; Yu, Chong-Jen

    2017-01-01

    Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)–1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activation. Partially blocking PD-1 and the PD ligand with antagonizing antibodies in the stimulation assay significantly increased the cytokine production of IFN-γ and decreased the apoptosis on T lymphocytes. In conclusion, the patients with MAC-LD have attenuated lymphocyte immunity, which might be associated with increasing activation of PD-1 and PD-1 ligand. Regulating such activation might improve the lymphocytic secretion of IFN-γ and reduce apoptosis. PMID:28169347

  17. Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

    PubMed

    Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

    2015-11-01

    It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

  18. Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Moon, Seong Mi; Kim, Su-Young; Lee, Soo-Youn; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-10-01

    Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Preliminary Evaluation of a Sitafloxacin-Containing Regimen for Relapsed or Refractory Pulmonary Mycobacterium avium Complex Disease

    PubMed Central

    Fujita, Kohei; Fujita, Masaki; Ito, Yutaka; Hirai, Toyohiro; Mio, Tadashi; Watanabe, Kentaro; Mishima, Michiaki

    2016-01-01

    Although sitafloxacin (STFX) is known to have a favorable minimum inhibitory concentration for Mycobacterium avium, few studies have evaluated the clinical efficacy of an STFX-containing regimen for pulmonary M avium complex (MAC) disease. To evaluate the clinical efficacy of STFX-containing regimens for relapsed or refractory pulmonary MAC disease, we retrospectively reviewed 18 patients with pulmonary MAC disease who received STFX for at least 4 weeks for pulmonary MAC disease between January 2008 and February 2016. Of 18 patients, 10 (55.6%) showed improved radiological characteristics and 8 (44.4%) showed negative sputum cultures at 6 months. Regarding the clinical symptoms, improvements were observed in decreasing order in sputum production (77.8%), cough (72.2%), and malaise (55.6%). Common adverse events included nausea or vomiting (38.9%), followed by loose stool or diarrhea (27.8%) and sleepiness (11.1%). Although this study contained a small number of subjects, we describe a STFX-containing regimen that was effective in achieving sputum culture negative conversions and had an acceptable adverse events profile. PMID:27704005

  20. Rapid Mycobacterial Liquid Culture-Screening Method for Mycobacterium avium Complex Based on Secreted Antigen-Capture Enzyme-Linked Immunosorbent Assay▿

    PubMed Central

    Shin, Sung Jae; Anklam, Kelly; Manning, Elizabeth J. B.; Collins, Michael T.

    2009-01-01

    Sensors in automated liquid culture systems for mycobacteria, such as MGIT, BacT/Alert 3D, and Trek ESP II, flag growth of any type of bacteria; a positive signal does not mean that the target mycobacteria are present. All signal-positive cultures thus require additional and often laborious testing. An immunoassay was developed to screen liquid mycobacterial cultures for evidence of Mycobacterium avium complex (MAC). The method, called the MAC-enzyme-linked immunosorbent assay (ELISA), relies on detection of MAC-specific secreted antigens in liquid culture. Secreted MAC antigens were captured by the MAC-ELISA with polyclonal anti- Mycobacterium avium subsp. paratuberculosis chicken immunoglobulin Y (IgY), detected using rabbit anti-MAC IgG, and then revealed using horseradish peroxidase-conjugated goat anti-rabbit IgG. When the MAC-ELISA was evaluated using pure cultures of known mycobacterial (n = 75) and nonmycobacterial (n = 17) organisms, no false-positive or false-negative MAC-ELISA results were found. By receiver operator characteristic (ROC) analysis of 1,275 previously identified clinical isolates, at the assay optimal cutoff the diagnostic sensitivity and specificity of the MAC-ELISA were 92.6% (95% confidence interval [95% CI], 90.3 to 94.5) and 99.9% (95% CI, 99.2 to 100), respectively, with an area under the ROC curve of 0.992. Prospective evaluation of the MAC-ELISA with an additional 652 clinical samples inoculated into MGIT ParaTB medium and signaling positive per the manufacturer's instructions found that the MAC-ELISA was effective in determining those cultures that actually contained MAC species and warranting the resources required to identify the organism by PCR. Of these 652 MGIT-positive cultures, the MAC-ELISA correctly identified 96.8% (of 219 MAC-ELISA-positive cultures) as truly containing MAC mycobacteria, based on PCR or high-performance liquid chromatography (HPLC) as reference tests. Only 6 of 433 MGIT signal-positive cultures (1

  1. Rapid mycobacterial liquid culture-screening method for Mycobacterium avium complex based on secreted antigen-capture enzyme-linked immunosorbent assay.

    PubMed

    Shin, Sung Jae; Anklam, Kelly; Manning, Elizabeth J B; Collins, Michael T

    2009-05-01

    Sensors in automated liquid culture systems for mycobacteria, such as MGIT, BacT/Alert 3D, and Trek ESP II, flag growth of any type of bacteria; a positive signal does not mean that the target mycobacteria are present. All signal-positive cultures thus require additional and often laborious testing. An immunoassay was developed to screen liquid mycobacterial cultures for evidence of Mycobacterium avium complex (MAC). The method, called the MAC-enzyme-linked immunosorbent assay (ELISA), relies on detection of MAC-specific secreted antigens in liquid culture. Secreted MAC antigens were captured by the MAC-ELISA with polyclonal anti- Mycobacterium avium subsp. paratuberculosis chicken immunoglobulin Y (IgY), detected using rabbit anti-MAC IgG, and then revealed using horseradish peroxidase-conjugated goat anti-rabbit IgG. When the MAC-ELISA was evaluated using pure cultures of known mycobacterial (n = 75) and nonmycobacterial (n = 17) organisms, no false-positive or false-negative MAC-ELISA results were found. By receiver operator characteristic (ROC) analysis of 1,275 previously identified clinical isolates, at the assay optimal cutoff the diagnostic sensitivity and specificity of the MAC-ELISA were 92.6% (95% confidence interval [95% CI], 90.3 to 94.5) and 99.9% (95% CI, 99.2 to 100), respectively, with an area under the ROC curve of 0.992. Prospective evaluation of the MAC-ELISA with an additional 652 clinical samples inoculated into MGIT ParaTB medium and signaling positive per the manufacturer's instructions found that the MAC-ELISA was effective in determining those cultures that actually contained MAC species and warranting the resources required to identify the organism by PCR. Of these 652 MGIT-positive cultures, the MAC-ELISA correctly identified 96.8% (of 219 MAC-ELISA-positive cultures) as truly containing MAC mycobacteria, based on PCR or high-performance liquid chromatography (HPLC) as reference tests. Only 6 of 433 MGIT signal-positive cultures (1

  2. Rapid susceptibility testing of mycobacterium avium complex and mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1993-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of the Human Immunodeficiency Virus (HIV) infection will continue to rise more rapidly worldwide than predicted earlier. The Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to diseases called opportunistic infections of which tuberculosis and M. avium Complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, Maryland, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. Therefore, we proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis. The work was initiated in June 1992. In the last report, we described our efforts in developing ATP assay method using MAC. Studies were continued further, and during the period of this report, we established the relationship between colony forming units and ATP levels of these organisms during the growth cycle. Also, we evaluated the effects of standard antimycobacterial drugs using ATP assay technique and compared the results with those obtained with conventional tube dilution proportional method.

  3. Rapid drug susceptibility of Mycobacterium avium complex using a fluorescence quenching method.

    PubMed

    Marone, P; Bono, L; Carretto, E; Barbarini, D; Telecco, S

    1997-08-01

    Mycobacteria Growth Indicator Tube (MGIT) is a recently introduced rapid growth detection method which uses an oxygen quenched fluorescent indicator. The present study evaluated the ability of this new method to determine the drug susceptibility of Mycobacterium avium complex (MAC). Thirty strains recovered from patients with AIDS were tested for susceptibility to clarithromycin, rifabutin, ciprofloxacin, azithromycin and amikacin using MGIT. Results were compared to susceptibilities determined by the agar dilution method. The results obtained showed a 100% correlation between MGIT and the agar dilution method for rifabutin and clarithromycin. There was a 100% correlation between the two methods for azithromycin against 27 strains. MGIT was well correlated with the agar dilution method for detecting resistance to clarithromycin, rifabutin and azithromycin in 4 days, but the correlation was poor when susceptibilities to ciprofloxacin and amikacin were determined. This rapid method is non-radiometric, noninvasive and does not require any special instruments.

  4. Novel Mycobacterium avium Complex Species Isolated From Black Wildebeest (Connochaetes gnou) in South Africa.

    PubMed

    Kabongo-Kayoka, P N; Obi, C L; Nakajima, C; Suzuki, Y; Hattori, T; Eloff, J N; Wright, J; Mbelle, N; McGaw, L J

    2017-06-01

    A study was undertaken to isolate and characterize Mycobacterium species from black wildebeest suspected of being infected with tuberculosis in South Africa. This led to the discovery of a new Mycobacterium avium complex species, provisionally referred to as the Gnou isolate from black wildebeest (Connochaetes gnou). Sixteen samples from nine black wildebeest were processed for Mycobacterium isolation. Following decontamination, samples were incubated in an ordinary incubator at 37°C on Löwenstein-Jensen slants and in liquid medium tubes using the BACTEC(™) MGIT(™) 960 system, respectively. Identification of the isolate was carried out by standard biochemical tests and using the line probe assay from the GenoType(®) CM/AS kit (Hain Lifescience GmbH, Nehren, Germany). The DNA extract was also analysed using gene sequencing. Partial gene sequencing and analysis of 16S rRNA gene, and 16S-23S rRNA (ITS), rpoB and hsp65 and phylogenetic analyses by searching GenBank using the BLAST algorithm were conducted. Phylogenetic trees were constructed using four methods, namely Bayesian inference, maximum likelihood, maximum parsimony and neighbour-joining methods. The isolate was identified as Mycobacterium intracellulare using the GenoType(®) CM/AS kit and as Mycobacterium avium complex (MAC) by gene sequencing. The gene sequence targeting all the genes, ITS, 16S rRNA, rpoB and hsp65 and phylogenetic analyses indicated that this isolate presented a nucleotide sequence different from all currently published sequences, and its position was far enough from other MAC species to suggest that it might be a new species. © 2015 Blackwell Verlag GmbH.

  5. Clinical and epidemiological correlates of genotypes within the Mycobacterium avium complex defined by restriction and sequence analysis of hsp65.

    PubMed

    Smole, Sandra C; McAleese, Fionnuala; Ngampasutadol, Jutamas; Von Reyn, C Fordham; Arbeit, Robert D

    2002-09-01

    Species identification of isolates of the Mycobacterium avium complex (MAC) remains a difficult task. Although M. avium and Mycobacterium intracellulare can be identified with expensive, commercially available probes, many MAC isolates remain unresolved, including those representing Mycobacterium lentiflavum as well as other potentially undefined species. PCR restriction analysis (PRA) of the hsp65 gene has been proposed as a rapid and inexpensive approach. We applied PRA to 278 MAC isolates, including 126 from blood of human immunodeficiency virus (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary isolates from a different study. A total of 15 different PRA patterns were observed. For 27 representative isolates, a 441-bp fragment of the hsp65 gene was sequenced; based on 54 polymorphic sites, 18 different alleles were defined, including 12 alleles not previously reported. Species and phylogenetic relationships were more accurately defined by sequencing than by PRA or commercial probe. The distribution of PRA types and, by implication, phylogenetic lineages among blood isolates was significantly different from that for pulmonary and environmental isolates, suggesting that particular lineages have appreciably greater virulence and invasive potential.

  6. Proton Magnetic Resonance Imaging for Initial Assessment of Isolated Mycobacterium avium Complex Pneumonia.

    PubMed

    Chung, Jonathan H; Huitt, Gwen; Yagihashi, Kunihiro; Hobbs, Stephen B; Faino, Anna V; Bolster, Bradley D; Biederer, Jürgen; Puderbach, Michael; Lynch, David A

    2016-01-01

    Computed tomographic (CT) radiography is the reference standard for imaging Mycobacterium avium complex (MAC) lung infection. Magnetic resonance imaging (MRI) has been shown to be comparable to CT for characterizing other pulmonary inflammatory conditions, but has not been rigorously tested for imaging MAC pneumonia. To determine the feasibility of pulmonary MRI for imaging MAC pneumonia and to assess the degree of agreement between MRI and CT for assessing the anatomic features and lobar extent of MAC lung infections. Twenty-five subjects with culture-confirmed MAC pneumonia and no identified coinfecting organisms were evaluated by thoracic MRI and then by chest CT imaging performed up to 1 week later. After deidentification, first the MRI and then the CT scans were scored 2 weeks apart by two chest radiologists working independently of one another. Discrepancies were resolved by a third chest radiologist. The scans were scored for bronchiectasis, consolidation or atelectasis, abscess or sacculation, nodules, and mucus plugging using a three-point lobar scale (absent, <50% of lobe, and >50% of lobe). Agreement analyses and ordinary least products regressions were performed. A fixed bias was found between total CT and MRI scores, with CT scoring higher on average (median difference: 4 on a scale of 48; interquartile range: 3, 6). Fixed biases were found for bronchiectasis and consolidation or atelectasis subscale scores. Both fixed and proportional biases were found between CT and MRI mucus plugging scores. No bias was found between CT and MRI nodule scores. There was nearly perfect lobar percent agreement for more conspicuous findings such as consolidation or atelectasis and abscess or sacculation. In this exploratory study of 25 adult patients with culture-proven MAC lung infection, we found moderate agreement between MRI and CT for assessing the anatomic features and lobar extent of disease. Given the feasibility of chest MRI for this condition, future work is

  7. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease.

    PubMed

    Jeong, Byeong-Ho; Jeon, Kyeongman; Park, Hye Yun; Kim, Su-Young; Lee, Kyung Soo; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2015-01-01

    Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited. To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for nodular bronchiectatic MAC lung disease. A retrospective cohort study of 217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung disease. All patients received either daily (n = 99) or intermittent therapy (n = 118) that included clarithromycin or azithromycin, rifampin, and ethambutol. Modification of the initial antibiotic therapy occurred more frequently in the daily therapy group than in the intermittent therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more frequently discontinued in the daily therapy group than in the intermittent therapy group (24 vs. 1%; P ≤ 0.001). However, the rates of symptomatic improvement, radiographic improvement, and sputum culture conversion were not different between the two groups (daily therapy vs. intermittent therapy: 75 vs. 82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In addition, the adjusted proportion of sputum culture conversion was similar between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P = 0.785). These results suggest that intermittent three-times-weekly therapy with a macrolide, rifampin, and ethambutol is a reasonable initial treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).

  8. Comparison of CO2 Generation (BACTEC) and Viable-Count Methods To Determine the Postantibiotic Effect of Antimycobacterial Agents against Mycobacterium avium Complex

    PubMed Central

    Zhanel, George G.; Saunders, Marilyn H.; Wolfe, Joyce N.; Hoban, Daryl J.; Karlowsky, James A.; Kabani, Amin M.

    1998-01-01

    The postantibiotic effects (PAEs) of antimycobacterial agents determined with a BACTEC TB-460 instrument (CO2 production) and by a traditional viable-count method against Mycobacterium avium complex (MAC) were not significantly different (P > 0.05). The longest PAEs following a 2-h exposure to 2× the MIC were induced by amikacin (10.3 h), rifampin (9.7 h), and rifabutin (9.5 h), while the shortest PAEs resulted from clofazimine (1.7 h) and ethambutol (1.1 h) exposure. CO2 generation is a valid and efficient means of determining in vitro PAEs against MAC. PMID:9449284

  9. Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations

    PubMed Central

    Almeida, Deepak V.; Tyagi, Sandeep; Converse, Paul J.; Ammerman, Nicole C.; Grosset, Jacques H.

    2015-01-01

    The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. PMID:25624335

  10. Dose response models and a quantitative microbial risk assessment framework for the Mycobacterium avium complex that account for recent developments in molecular biology, taxonomy, and epidemiology.

    PubMed

    Hamilton, Kerry A; Weir, Mark H; Haas, Charles N

    2017-02-01

    Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified, and selected for more human-virulent characteristics by amoeba species in aquatic biofilms. However, a quantitative microbial risk assessment (QMRA) has not been performed due to the lack of dose response models resulting from significant heterogeneity within even a single species or subspecies of MAC, as well as the range of human susceptibilities to mycobacterial disease. The primary human-relevant species and subspecies responsible for the majority of the human disease burden and present in drinking water, biofilms, and soil are M. avium subsp. hominissuis, M. intracellulare, and M. chimaera. A critical review of the published literature identified important health endpoints, exposure routes, and susceptible populations for MAC risk assessment. In addition, data sets for quantitative dose-response functions were extracted from published in vivo animal dosing experiments. As a result, seven new exponential dose response models for human-relevant species of MAC with endpoints of lung lesions, death, disseminated infection, liver infection, and lymph node lesions are proposed. Although current physical and biochemical tests used in clinical settings do not differentiate between M. avium and M. intracellulare, differentiating between environmental species and subspecies of the MAC can aid in the assessment of health risks and control of MAC sources. A framework is proposed for incorporating the proposed dose response models into susceptible population- and exposure route-specific QMRA models.

  11. Draft genome sequence of a Mycobacterium avium complex isolate from a broadbill bird

    USDA-ARS?s Scientific Manuscript database

    We report the draft genome sequences of ten Mycobacterium avium complex isolates obtained from diverse hosts. This collection includes isolates obtained from deer, pig, elephant, ruddy duck and Red-tailed hawk species. The type strain of Mycobacterium avium subspecies silvaticum (ATCC 49884) is also...

  12. Evaluation of Vitek MS for rapid classification of clinical isolates belonging to Mycobacterium avium complex.

    PubMed

    Boyle, Daniel P; Zembower, Teresa R; Qi, Chao

    2015-01-01

    We evaluated the ability of the Vitek MS system to classify clinical pulmonary Mycobacterium avium complex isolates compared to multilocus sequence analysis. Vitek MS accurately identified 55% of the isolates as M. avium and 18% as M. intracellulare, but misidentified 24 (27%) Mycobacterium chimaera isolates as Mycobacterium intracellulare.

  13. Descriptive analysis of the prevalence and the molecular epidemiology of Mycobacterium avium complex-infected pigs that were slaughtered on the main island of Okinawa.

    PubMed

    Hibiya, K; Kazumi, Y; Nishiuchi, Y; Sugawara, I; Miyagi, K; Oda, Y; Oda, E; Fujita, J

    2010-09-01

    Recent genetic studies have revealed that several epidemiological factors affect Mycobacterium avium complex (MAC) infection in pig populations. However, mechanisms underlying the spread of MAC infection among hog farms have not been clarified. In consideration of this situation, we cross-sectionally investigated the mechanisms underlying the spread of MAC on the island of Okinawa. Pigs slaughtered (n=706,763) and 331 hog farms on Okinawa were surveyed during the years 2002-2004. Two outbreaks of MAC infection were occurred in several farms during survey period. Bacteria were isolated from randomly selected pigs and genotype of isolates was determined by using genetic finger printing methods with the insertion sequence (IS) 1245 restriction fragment length polymorphism (RFLP). Most isolates had large numbers of IS1245 copies, while strains with low copy numbers of IS1245 and isolates without IS1245 were seen in few farms. MACs strains were repeatedly isolated from pigs of the affected farms during the survey period. Those farms with an identical pig rearing systems showed synchronic changes in the prevalence of MAC infection. An industrial farm without an outbreak had an independent pig flow, but maintained distinct MAC strains. Multivariate analysis did not reveal independent factors for the prevalence of the MAC infection. These findings suggest that there were three clusters distinguished genetically in the main island of Okinawa, which were potentially spread by common pig flow. However, the outbreaks occurred because of unspecified conditions on each farm environment.

  14. Thin-section CT findings of nontuberculous mycobacterial pulmonary diseases: comparison between Mycobacterium avium-intracellulare complex and Mycobacterium abscessus infection.

    PubMed

    Chung, Myung Jin; Lee, Kyung Soo; Koh, Won-Jung; Lee, Ju Hyun; Kim, Tae Sung; Kwon, O Jung; Kim, Seonwoo

    2005-10-01

    We aimed to compare the CT findings of nontuberculous mycobacterial pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. Two chest radiologists analyzed retrospectively the thin-section CT findings of 51 patients with MAC and 36 with M. abscessus infection in terms of patterns and forms of lung lesions. No significant difference was found between MAC and M. abscessus infection in the presence of small nodules, tree-in-bud pattern, and bronchiectasis. However, lobar volume decrease (p=0.001), nodule (p=0.018), airspace consolidation (p=0.047) and thin-walled cavity (p=0.009) were more frequently observed in MAC infection. The upper lobe cavitary form was more frequent in the MAC (19 of 51 patients, 37%) group than M. abscessus (5 of 36, 14%) (p=0.029), whereas the nodular bronchiectatic form was more frequent in the M. abscessus group ([29 of 36, 81%] vs. [27 of 51, 53%] in MAC) (p=0.012). In conclusion, there is considerable overlap in common CT findings of MAC and M. abscessus pulmonary infection; however, lobar volume loss, nodule, airspace consolidation, and thin-walled cavity are more frequently seen in MAC than M. abscessus infection.

  15. Use of the INNO-LiPA-MYCOBACTERIA assay (version 2) for identification of Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum complex isolates.

    PubMed

    Lebrun, Léa; Weill, François-Xavier; Lafendi, Leila; Houriez, Florence; Casanova, François; Gutierrez, M Cristina; Ingrand, Didier; Lagrange, Philippe; Vincent, Véronique; Herrmann, Jean Louis

    2005-06-01

    Using INNO-LiPA-MYCOBACTERIA (Lipav1; Innogenetics) and the AccuProbe (Gen-Probe Inc./bioMérieux) techniques, 35 Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum (MAC/MAIS) complex strains were identified between January 2000 and December 2002. Thirty-four of 35 isolates were positive only for the MAIS complex probe by Lipav1 and were further analyzed by INNO-LiPA-MYCOBACTERIA version 2 (Lipav2), hsp65 PCR restriction pattern analysis (PRA), and ribosomal internal transcribed spacer (ITS), hsp65, and 16S rRNA sequences. Lipav2 identified 14 of 34 strains at the species level, including 11 isolates positive for the newly specific MAC sequevar Mac-A probe (MIN-2 probe). Ten of these 11 isolates corresponded to sequevar Mac-A, which was recently defined as Mycobacterium chimerae sp. nov. Among the last 20 of the 34 MAIS isolates, 17 (by hsp65 PRA) and 18 (by hsp65 sequence) were characterized as M. avium. Ten of the 20 were identified as Mac-U sequevar. All these 20 isolates were identified as M. intracellulare by 16S rRNA sequence except one isolate identified as Mycobacterium paraffinicum by 16S rRNA and ITS sequencing. One isolate out of 35 isolates that was positive for M. avium by AccuProbe and that was Mycobacterium genus probe positive and MAIS probe negative by Lipav1 and Lipav2 might be considered a new species. In conclusion, the new INNO-LiPA-MYCOBACTERIA allowed the identification of 40% of the previously unidentified MAIS isolates at the species level. The results of the Lipav2 assay on the MAIS isolates confirm the great heterogeneity of this group and suggest the use of hsp65 or ITS sequencing for precise identification of such isolates.

  16. Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine.

    PubMed Central

    Brown, S T; Edwards, F F; Bernard, E M; Tong, W; Armstrong, D

    1993-01-01

    Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections. PMID:8384809

  17. Characterization of clinical and environmental Mycobacterium avium spp. isolates and their interaction with human macrophages

    EPA Science Inventory

    Members of the Mycobacterium avium complex (MAC) are naturally occurring bacteria in the environment. A link has been suggested between M. avium strains in drinking water and clinical isolates from infected individuals. There is a need to develop new screening methodologies tha...

  18. Characterization of clinical and environmental Mycobacterium avium spp. isolates and their interaction with human macrophages

    EPA Science Inventory

    Members of the Mycobacterium avium complex (MAC) are naturally occurring bacteria in the environment. A link has been suggested between M. avium strains in drinking water and clinical isolates from infected individuals. There is a need to develop new screening methodologies tha...

  19. Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity.

    PubMed

    Timms, Verlaine J; Hassan, Karl A; Mitchell, Hazel M; Neilan, Brett A

    2015-09-15

    A human isolate of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis 43525) was sequenced and compared genomically to other mycobacterial pathogens. M. paratuberculosis 43525 was recently isolated from a patient with ulcerative colitis and belongs to the M. avium complex, a group known to infect both humans and animals. While M. paratuberculosis is a known pathogen of livestock, there are only 20 human isolates from the last 20 years, therefore we took the opportunity to perform a whole genome comparison between human and animal mycobacterial pathogens. We also compared virulence determinants such as the mycobactin cluster, PE/PPE genes and mammalian cell entry (mce) operons between MAC subspecies that infect animals and those that infect humans. M. tuberculosis was also included in these analyses given its predominant role as a human pathogen. This genome comparison showed the PE/PPE profile of M. paratuberculosis 43525 to be largely the same as other M. paratuberculosis isolates, except that it had one PPE and one PE_PGRS protein that are only present in human MAC strains and M. tuberculosis. PE/PPE proteins that were unique to M. paratuberculosis 43525, M. avium subsp. hominissuis and a caprine M. paratuberculosis isolate, were also identified. In addition, the mycobactin cluster differed between human and animal isolates and a unique mce operon flanked by two mycobactin genes, mbtA and mbtJ, was identified in all available M. paratuberculosis genomes. Despite the whole genome comparison placing M. paratuberculosis 43525 as closely related to bovine M. paratuberculosis, key virulence factors were similar to human mycobacterial pathogens. This study highlights key factors of mycobacterial pathogenesis in humans and forms the basis for future functional studies.

  20. Characterization and growth in human macrophages of Mycobacterium avium complex strains isolated from the blood of patients with acquired immunodeficiency syndrome.

    PubMed Central

    Meylan, P R; Richman, D D; Kornbluth, R S

    1990-01-01

    Strains of the Mycobacterium avium complex (MAC) yield opaque and transparent colonial variants when cultivated in vitro. The transparent variants are more virulent than the opaque for animals, but little is known about the respective roles of these colonial variants in humans. To assess which variant infects humans, various blood fractions from eight patients with MAC bacteremia were plated directly onto 7H10 agar. In cell fractionation studies, all the M. avium complex CFU were associated with leukocytes and none were found free in plasma. All colonies on the primary culture plate exhibited the transparent phenotype. However, during subculture in 7H9 broth or on Lowenstein-Jensen agar, opaque variants appeared in seven of eight strains. Isogenic pairs of transparent and opaque variants were prepared and used to infect in vitro human monocyte-derived macrophages from healthy seronegative individuals. Transparent variants invariably grew inside macrophages, but only one of seven opaque variants did so. These observations indicate that the bacteremia of M. avium complex in acquired immunodeficiency syndrome patients consists exclusively of the transparent variants, perhaps because these variants are able to multiply inside macrophages. In contrast, opaque variants appear after in vitro subculture and are controlled by human macrophages, consistent with their reduced virulence in animals. Images PMID:2370109

  1. Clinical Characteristics, Treatment Outcomes, and Resistance Mutations Associated with Macrolide-Resistant Mycobacterium avium Complex Lung Disease.

    PubMed

    Moon, Seong Mi; Park, Hye Yun; Kim, Su-Young; Jhun, Byung Woo; Lee, Hyun; Jeon, Kyeongman; Kim, Dae Hun; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Lee, Seung-Heon; Kim, Chang Ki; Shin, Sung Jae; Daley, Charles L; Koh, Won-Jung

    2016-11-01

    Macrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due to Mycobacterium avium complex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form. M. intracellulare was the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. [Identification of Mycobacterium avium-intracellulare complex by PCR of AIDS and disseminated mycobacteriosis].

    PubMed

    García-Elorriaga, Guadalupe; Degollado-Estrada, Edgar; Villagómez-Ruiz, Alfredo; Cortés-Torres, Nancy; Arreguín-Reséndiz, Lilián; Del Rey-Pineda, Guillermo; González-Bonilla, César

    2016-01-01

    Introducción: el objetivo de este artículo es Identificar y diferenciar el complejo MAC por PCR en pacientes con SIDA y micobacteriosis diseminada. Métodos: se llevó a cabo un estudio transversal para identificar MAC por biología molecular. Se sintetizaron dos conjuntos de iniciadores: MAV y MIN, para M. avium y M. intracellulare, respectivamente. El ADN total de células obtenidas de 29 aislados clínicos y muestras de suero de otros 24 pacientes con SIDA e infección micobacteriana diseminada fue extraído y se amplificó por PCR con los iniciadores MAV y MIN. Cada uno de los iniciadores MAV y MIN amplificó un segmento altamente específico de 1.3 kb del ADN homólogo, respectivamente. Resultados: veintinueve ADN de los aislados clínicos de MAC identificadas por Gen-Probe AccuProbes se amplificaron con los iniciadores MAV (M. avium). De las 24 muestras clínicas, 3 fueron positivas para M. avium y 6 para M. tuberculosis. Conclusiones: nuestros resultados demostraron que la técnica de PCR se puede aplicar para la diferenciación de M. avium y M. intracellulare por iniciadores específicos 16S rRNA. En pacientes con estadio avanzado de SIDA y en quienes se sospecha micobacteriosis diseminada, la presencia de anemia (incluso con cultivos negativos) fosfatasa alcalina elevada y una mediana de CD4 de 15.9/ml, se debe considerar seriamente el diagnóstico de infección por MAC; sugerimos que, de acuerdo con nuestros resultados, se justifica una estratificación más precisa de los pacientes en términos de sus recuentos de células T CD4.

  3. Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

    PubMed Central

    González-Pérez, Mónica; Mariño-Ramírez, Leonardo; Parra-López, Carlos Alberto; Murcia, Martha Isabel; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Míguez, Yadira; Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara

    2013-01-01

    The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue. PMID:23959717

  4. Evaluation of a high-throughput repetitive-sequence-based PCR system for DNA fingerprinting of Mycobacterium tuberculosis and Mycobacterium avium complex strains.

    PubMed

    Cangelosi, Gerard A; Freeman, Robert J; Lewis, Kaeryn N; Livingston-Rosanoff, Devon; Shah, Ketan S; Milan, Sparrow Joy; Goldberg, Stefan V

    2004-06-01

    Repetitive-sequence-based PCR (rep-PCR) is useful for generating DNA fingerprints of diverse bacterial and fungal species. Rep-PCR amplicon fingerprints represent genomic segments lying between repetitive sequences. A commercial system that electrophoretically separates rep-PCR amplicons on microfluidic chips, and provides computer-generated readouts of results has been adapted for use with Mycobacterium species. The ability of this system to type M. tuberculosis and M. avium complex (MAC) isolates was evaluated. M. tuberculosis strains (n = 56) were typed by spoligotyping with rep-PCR as a high-resolution adjunct. Results were compared with those generated by a standard approach of spoligotyping with IS6110-targeted restriction fragment length polymorphism (IS6110-RFLP) as the high-resolution adjunct. The sample included 11 epidemiologically and genotypically linked outbreak isolates and a population-based sample of 45 isolates from recent immigrants to Seattle, Wash., from the African Horn countries of Somalia, Eritrea, and Ethiopia. Twenty isolates exhibited unique spoligotypes and were not analyzed further. Of the 36 outbreak and African Horn isolates with nonunique spoligotypes, 23 fell into four clusters identified by IS6110-RFLP and rep-PCR, with 97% concordance observed between the two methods. Both approaches revealed extensive strain heterogeneity within the African Horn sample, consistent with a predominant pattern of reactivation of latent infections in this immigrant population. Rep-PCR exhibited 89% concordance with IS1245-RFLP typing of 28 M. avium subspecies avium strains. For M. tuberculosis as well as M. avium subspecies avium, the discriminative power of rep-PCR equaled or exceeded that of RFLP. Rep-PCR also generated DNA fingerprints from M. intracellulare (n = 8) and MAC(x) (n = 2) strains. It shows promise as a fast, unified method for high-throughput genotypic fingerprinting of multiple Mycobacterium species.

  5. Dual color fluorescence in situ hybridization (FISH) assays for detecting Mycobacterium tuberculosis and Mycobacterium avium complexes and related pathogens in cultures.

    PubMed

    Shah, Jyotsna; Weltman, Helena; Narciso, Patricia; Murphy, Christina; Poruri, Akhila; Baliga, Shrikala; Sharon, Leesha; York, Mary; Cunningham, Gail; Miller, Steve; Caviedes, Luz; Gilman, Robert; Desmond, Edward; Ramasamy, Ranjan

    2017-01-01

    Two rapid dual color fluorescence in situ hybridization (FISH) assays were evaluated for detecting M. tuberculosis and related pathogens in cultures. The MN Genus-MTBC FISH assay uses an orange fluorescent probe specific for the Mycobacterium tuberculosis complex (MTBC) and a green fluorescent probe specific for the Mycobacterium and Nocardia genera (MN Genus) to detect and distinguish MTBC from other Mycobacteria and Nocardia. A complementary MTBC-MAC FISH assay uses green and orange fluorescent probes specific for the MTBC and M. avium complex (MAC) respectively to identify and differentiate the two species complexes. The assays are performed on acid-fast staining bacteria from liquid or solid cultures in less than two hours. Forty-three of 44 reference mycobacterial isolates were correctly identified by the MN Genus-specific probe as Mycobacterium species, with six of these correctly identified as MTBC with the MTBC-specific probe and 14 correctly as MAC by the MAC-specific probe. Of the 25 reference isolates of clinically relevant pathogens of other genera tested, only four isolates representing two species of Corynebacterium gave a positive signal with the MN Genus probe. None of these 25 isolates were detected by the MTBC and MAC specific probes. A total of 248 cultures of clinical mycobacterial isolates originating in India, Peru and the USA were also tested by FISH assays. DNA sequence of a part of the 23S ribosomal RNA gene amplified by PCR was obtained from 243 of the 248 clinical isolates. All 243 were confirmed by DNA sequencing as Mycobacterium species, with 157 and 50 of these identified as belonging to the MTBC and the MAC, respectively. The accuracy of the MN Genus-, MTBC-and MAC -specific probes in identifying these 243 cultures in relation to their DNA sequence-based identification was 100%. All ten isolates of Nocardia, (three reference strains and seven clinical isolates) tested were detected by the MN Genus-specific probe but not the MTBC- or

  6. [A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex with a giant gravitation abscess].

    PubMed

    Kawaguchi, H; Torii, Y; Senda, Y; Totani, Y; Suzuki, M; Ooshika, H; Wakayama, H; Ito, Y; Noguchi, M

    1994-02-01

    A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex (MAC) was reported. The case was a female of 52 years of age. She was admitted to our hospital due to high fever and polyarthralgia. Her chest X-ray and CT scan revealed infiltrative shadows in the right S2b and S4 segments, and multiple accumulation shadows were seen on osteoscintigraphy. Pus aspirated from a lesion of the right fifth rib were acid-fast bacilli positive by smear (Gaffky v). The administration of four drugs, INH, RFP, EB and SM, was introduced, then corticosteroid was added, and the case became afebrile. Later, acid-fast bacilli were also isolated from bronchial washing and aspirated specimen from bone marrow, and all of them were identified as MAC. Based on these findings, the case was diagnosed as generalized disseminated mycobacteriosis. After several months remission, tenderness over the fifth lumbar vertebra deteriorated, and MRI scan on lumbar vertebrae showed high-intensity area both on T1-weighted and T2-weighted images. MAC was isolated from the pus of the fifth lumbar vertebra. Lumbar lesions deteriorated gradually, and a giant gravitation abscess which involved right ilium was revealed by CT scan of the pelvis. In spite of vigorous treatment including chemotherapy, aspiration of pus and drainage, general condition of the case deteriorated, and the case finally died of renal insufficiency.

  7. Distribution of IS901 in strains of Mycobacterium avium complex from swine by using IS901-detecting primers that discriminate between M. avium and Mycobacterium intracellulare.

    PubMed

    Nishimori, K; Eguchi, M; Nakaoka, Y; Onodera, Y; Ito, T; Tanaka, K

    1995-08-01

    The presence of the mycobacterial insertion sequence IS901 was studied by PCR with reference strains of Mycobacterium avium complex; 122 veterinary strains of mycobacteria, mainly M. avium complex, isolated from swine; and 15 clinical strains. Four kinds of DNA extraction methods for PCR were compared. Use of the commercial extraction matrix allowed for the faster and easier preparation of PCR-amplifiable DNA than use of NaOH heating extraction or sodium dodecyl sulfate extraction of pretreated mycobacteria. It also provided more effective protection than boiling extraction against the destruction of DNA. Four reference strains of serovars 1 to 3 possessed IS901. Nine reference strains of serovars 1, 4 to 6, 8 to 11, and 21 possessed only IS901 insertion sites. A novel PCR product was found in the other reference strains of serovars 7, 12 to 17, 19, and 20 and two clinical strains of serovar 15. It is suggested that the primers that amplified the insertion portion of IS901 divided the M. avium complex into M. avium, Mycobacterium intracellulare, and other mycobacteria. None of the 110 strains of M. avium complex isolated from swine possessed IS901. It is suggested that the absence of IS901 might be characteristic of swine-derived strains of M. avium complex.

  8. Investigation of Spa Pools Associated with Lung Disorders Caused by Mycobacterium avium Complex in Immunocompetent Adults

    PubMed Central

    Lumb, Richard; Stapledon, Richard; Scroop, Andrew; Bond, Peter; Cunliffe, David; Goodwin, Allan; Doyle, Robyn; Bastian, Ivan

    2004-01-01

    Three cases of Mycobacterium avium complex-related lung disorders were associated with two poorly maintained spa pools by genotypic investigations. Inadequate disinfection of the two spas had reduced the load of environmental bacteria to less than 1 CFU/ml but allowed levels of M. avium complex of 4.3 × 104 and 4.5 × 103 CFU/ml. Persistence of the disease-associated genotype was demonstrated in one spa pool for over 5 months until repeated treatments with greater than 10 mg of chlorine per liter for 1-h intervals eliminated M. avium complex from the spa pool. A fourth case of Mycobacterium avium complex-related lung disease was associated epidemiologically but not genotypically with another spa pool that had had no maintenance undertaken. This spa pool contained low numbers of mycobacteria by smear and was culture positive for M. avium complex, and the nonmycobacterial organism count was 5.2 × 106 CFU/ml. Public awareness about the proper maintenance of private (residential) spa pools must be promoted by health departments in partnership with spa pool retailers. PMID:15294830

  9. Polyclonal infections due to Mycobacterium avium complex in patients with AIDS detected by pulsed-field gel electrophoresis of sequential clinical isolates.

    PubMed Central

    Slutsky, A M; Arbeit, R D; Barber, T W; Rich, J; von Reyn, C F; Pieciak, W; Barlow, M A; Maslow, J N

    1994-01-01

    Invasive infection with organisms of the Mycobacterium avium complex (MAC) is common among patients with advanced human immunodeficiency virus infection. In previous studies, we analyzed multiple individual colonies of MAC isolated from specimens obtained at the same time and observed that 14 to 20% of patients are simultaneously infected with more than one strain. In this study, we examined sequential isolates from 12 patients with AIDS who had two or more MAC isolates available from clinical specimens collected more than 1 week apart; the intervals between the first and last specimens ranged from 8 to 192 (median, 46) days. For each isolate, restriction digests of genomic DNA were analyzed by pulsed-field gel electrophoresis; DNA was prepared by using a protocol, described here in detail, which had been optimized for conditions of bacterial growth and lysis. The pulsed-field gel electrophoresis analysis identified four patients (33%) infected with two different MAC strains. Both M. avium and M. intracellulare were cultured from blood specimens from two patients. In each of the four patients, the second strain was identified from a culture taken within 14 days of the initial study isolate, and in three of these patients, the first strain was detected again in a subsequent culture. These observations suggest that the presence of two different strains among isolates from sequential cultures may reflect ongoing polyclonal infection. We conclude that polyclonal infection with MAC is common among patients with AIDS. The identification of such infections may be critical in the development of effective treatments. Images PMID:7929773

  10. Whole chromosomal DNA probes for rapid identification of Mycobacterium tuberculosis and Mycobacterium avium complex.

    PubMed Central

    Roberts, M C; McMillan, C; Coyle, M B

    1987-01-01

    Whole chromosomal DNA probes were used to identify clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium complex, and Mycobacterium gordonae. The probe for M. tuberculosis was prepared from Mycobacterium bovis BCG, which has been shown to be closely related to M. tuberculosis. A probe for the M. avium complex was prepared from three strains representing each of the three DNA homology groups in the M. avium complex. The probes were used in dot blot assays to identify clinical isolates of mycobacteria. The dot blot test correctly identified 57 of the 61 (93%) cultures grown on solid media, and 100% of antibiotic-treated broth-grown cells were correctly identified. Identification by dot blot required a maximum of 48 h. When the probes were tested against 63 positive BACTEC (Johnston Laboratories, Inc., Towson, Md.) cultures of clinical specimens, 59% were correctly identified. However, of the 14 BACTEC cultures that had been treated with antibiotics before being lysed, 13 (93%) were correctly identified. PMID:3112180

  11. Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis

    PubMed Central

    1983-01-01

    The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral

  12. Envelope protein complexes of Mycobacterium avium subsp. paratuberculosis and their antigenicity

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic enteric disease of ruminant animals. In the present study, blue native PAGE electrophoresis and 2D SDS-PAGE were used to separate MAP envelope protein complexes, followed by mass spectrometry (MS) ...

  13. Structure of a New Glycolipid from the Mycobacterium avium-Mycobacterium intracellulare Complex

    PubMed Central

    Watanabe, Motoko; Ohta, Akihiro; Sasaki, Shun-ichi; Minnikin, David E.

    1999-01-01

    From the lipid fraction of a freeze-dried cell mass of a strain of the Mycobacterium avium-Mycobacterium intracellulare complex, a new glycolipid was isolated and was characterized as 5-mycoloyl-α-arabinofuranosyl (1→1′)-glycerol, mainly on the basis of nuclear magnetic resonance spectroscopy studies. PMID:10094713

  14. Improved detection of Mycobacterium avium complex with the Bactec radiometric system

    SciTech Connect

    Hoffner, S.E.

    1988-05-01

    A reconsideration of the laboratory methods used for primary isolation of mycobacteria other than Mycobacterium tuberculosis is needed due to the increasingly recognized importance of such mycobacterial infections in immunocompromised patients. One example of this is the severe opportunistic infections caused by Mycobacterium avium complex among AIDS patients. In this study, the Bactec radiometric system was compared to conventional culture on solid medium for the detection of M. avium complex in 3,612 selected clinical specimens, mainly of extrapulmonary origin. Of a total number of 63 M. avium complex isolates, the Bactec system detected 58 (92%), compared to 37 (59%) for conventional culture. A much more rapid detection was attained with radiometric technique than with conventional culture. The mean detection time for the cultures positive with both methods was 7.1 and 28.3 days, respectively. The Bactec radiometric system achieves a rapid and significantly more sensitive detection and seems to be an excellent complement to conventional culture in the laboratory diagnosis of infections with the M. avium complex.

  15. High-resolution CT findings of Mycobacterium avium-intracellulare complex pulmonary disease: correlation with pulmonary function test results.

    PubMed

    Song, Jong Woon; Koh, Won-Jung; Lee, Kyung Soo; Lee, Ji Young; Chung, Myung Jin; Kim, Tae Sung; Kwon, O Jung

    2008-10-01

    The purpose of our study was to analyze the high-resolution CT findings of the nodular bronchiectatic form of Mycobacterium avium-intracellulare complex (MAC) pulmonary disease and to correlate the extent of high-resolution CT findings with pulmonary function test (PFT) results. From January 2005 through December 2005, we identified 47 patients (mean age, 58 +/- 13 years; age range, 24-72 years; male-female ratio, 11:36) with the nodular bronchiectatic form of MAC pulmonary disease who underwent both high-resolution CT and PFTs. High-resolution CT findings were reviewed retrospectively in terms of the presence and extent of bronchiectasis, cellular or inflammatory bronchiolitis (centrilobular small nodules and tree-in-bud signs), cavity, nodule, and other findings. The extent of the abnormalities seen on high-resolution CT was scored by modifying the cystic fibrosis scoring system proposed by Helbich and coworkers. The scores were correlated with PFT results using Spearman's correlation coefficient. On high-resolution CT, the three most frequently observed patterns of parenchymal abnormalities were, in decreasing order of frequency, cellular bronchiolitis (n = 47, 100%), bronchiectasis (n = 46, 98%), and consolidation (n = 27, 57%). The total CT score showed a significant correlation with the residual volume-total lung capacity (RV/TLC) ratio (r = 0.572, p < 0.001), forced expiratory volume in 1 second (FEV(1)) value (r = -0.426, p = 0.003), forced vital capacity (FVC) value (r = -0.360, p = 0.013), peak expiratory flow value (r = -0.352, p = 0.015), and peak expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75%)) (r = -0.289, p = 0.049). CT scoring of pulmonary abnormalities correlates with measures of functional impairment in patients with MAC pulmonary disease.

  16. Changes in Serum IgA Antibody Levels against the Glycopeptidolipid Core Antigen during Antibiotic Treatment of Mycobacterium avium Complex Lung Disease.

    PubMed

    Jhun, Byung Woo; Kim, Su-Young; Park, Hye Yun; Jeon, Kyeongman; Shin, Sung Jae; Koh, Won-Jung

    2017-03-28

    We evaluated serial changes in the levels of serum immunoglobulin A (IgA) antibody to the glycopeptidolipid (GPL) core antigen during antibiotic treatment in 57 patients with M. avium complex (MAC) lung disease, at baseline (T0) and after 3 months (T3) and 6 months (T6) of treatment. The median patient age was 59 years and 37 (65%) were female. Etiologic organisms included M. avium in 32 (56%) patients and M. intracellulare in 25 (44%). Seven (12%) patients had the fibrocavitary form of the disease on computed tomography. After 12 months of treatment, 42 (74%) patients achieved favorable responses, whereas 15 (26%) patients had unfavorable responses defined as no sputum culture conversion within 12 months of treatment. The initial median serum anti-GPL IgA levels in the 57 patients was 3.50 U/mL, and measurements at T0 (median 3.50 U/mL), T3 (median 2.71 U/mL), and T6 (median 2.61 U/mL) revealed significant decreases following treatment (P < 0.001). Multivariate analysis showed that an initially elevated anti-GPL IgA level (> 3.50 U/mL) was associated with an unfavorable response (P = 0.049). Our data suggest that elevated anti-GPL IgA levels may reflect disease activity, which may help to predict treatment response in patients with MAC lung disease.

  17. Tuberculosis in swine co-infected with Mycobacterium avium subsp. hominissuis and Mycobacterium bovis in a cluster from Argentina.

    PubMed

    Barandiaran, S; Pérez, A M; Gioffré, A K; Martínez Vivot, M; Cataldi, A A; Zumárraga, M J

    2015-04-01

    SUMMARY In Argentina little is known about the epidemiology of tuberculosis (TB) infection in swine. We characterized the epidemiological dynamics of Mycobacterium avium complex (MAC) infection in a swine population of Argentina using molecular tools and spatial analysis techniques. Isolates (n = 196) obtained from TB-like lesions (n = 200) were characterized by polymerase chain reaction. The isolates were positive to either M. bovis (IS6110) (n = 160) or M. avium (IS1245) (n = 16) while the remaining 20 (10.2%) isolates were positive to both M. bovis and M. avium. The detection of both bacteria together suggests co-infection at the animal level. In addition, MAC-positive isolates (n = 36) were classified as M. avium subsp. avium (MAA) (n = 30) and M. avium subsp. hominissuis (MAH) (n = 6), which resulted in five genotypes when they were typed using mycobacterial interspersed repetitive unit, variable number of tandem repeats (MIRU-VNTR). One significant (P = 0.017) spatial clustering of genotypes was detected, in which the proportion of MAH isolates was larger than expected under the null hypothesis of even distribution of genotypes. These results show that in Argentina the proportion of TB cases in pigs caused by M. avium is larger than that reported in earlier studies. The proportion of M. bovis-MAC co-infections was also higher than in previous reports. These results provide valuable information on the epidemiology of MAC infection in swine in Argentina.

  18. Determination of Genotypic Diversity of Mycobacterium avium Subspecies from Human and Animal Origins by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat and IS1311 Restriction Fragment Length Polymorphism Typing Methods ▿ †

    PubMed Central

    Radomski, Nicolas; Thibault, Virginie C.; Karoui, Claudine; de Cruz, Krystel; Cochard, Thierry; Gutiérrez, Cristina; Supply, Philip; Biet, Frank; Boschiroli, María Laura

    2010-01-01

    Members of the Mycobacterium avium complex (MAC) are ubiquitous bacteria that can be found in water, food, and other environmental samples and are considered opportunistic pathogens for numerous animal species, mainly birds and pigs, as well as for humans. We have recently demonstrated the usefulness of a PCR-based mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing for the molecular characterization of M. avium subsp. paratuberculosis and M. avium strains exclusively isolated from AIDS patients. In the present study we extended our analysis, based on eight MIRU-VNTR markers, to a strain collection comprehensively comprising the other M. avium subspecies, including M. avium subsp. avium, M. avium subsp. hominissuis, and M. avium subsp. silvaticum, isolated from numerous animal species, HIV-positive and HIV-negative humans, and environmental sources. All strains were fully typeable, with the discriminatory index being 0.885, which is almost equal to that obtained by IS1311 restriction fragment length polymorphism (RFLP) typing as a reference. In contrast to IS1311 RFLP typing, MIRU-VNTR typing was able to further discriminate M. avium subsp. avium strains. MIRU-VNTR alleles strongly associated with or specific for M. avium subspecies were detected in several markers. Moreover, the MIRU-VNTR typing-based results were consistent with a scenario of the independent evolution of M. avium subsp. avium/M. avium subsp. silvaticum and M. avium subsp. paratuberculosis from M. avium subsp. hominissuis, previously proposed on the basis of multilocus sequence analysis. MIRU-VNTR typing therefore appears to be a convenient typing method capable of distinguishing the three main subspecies and strains of the complex and providing new epidemiological knowledge on MAC. PMID:20107094

  19. Utilization of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) to Identify environmental Strains of Mycobacterium Complex

    EPA Science Inventory

    Species within the Mycobacterium avium Complex (MAC) group are found to be both prevalent and persistent in drinking water distribution systems. The MAC is composed of two predominant species: M. avium and M. intracellulare. These species have the ability to survive drinking ...

  20. Utilization of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) to Identify environmental Strains of Mycobacterium Complex

    EPA Science Inventory

    Species within the Mycobacterium avium Complex (MAC) group are found to be both prevalent and persistent in drinking water distribution systems. The MAC is composed of two predominant species: M. avium and M. intracellulare. These species have the ability to survive drinking ...

  1. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis.

    PubMed

    Shibata, Yuji; Horita, Nobuyuki; Yamamoto, Masaki; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Narita, Atsuya; Kanai, Akinori; Sato, Takashi; Kaneko, Takeshi

    2016-07-04

    Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6-52.8, I(2) = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837-0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621-0.761) and 0.906 (95% CI 0.836-0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1-13.8) and 0.34 (95% CI 0.26-0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value.

  2. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis

    PubMed Central

    Shibata, Yuji; Horita, Nobuyuki; Yamamoto, Masaki; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Narita, Atsuya; Kanai, Akinori; Sato, Takashi; Kaneko, Takeshi

    2016-01-01

    Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6–52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837–0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621–0.761) and 0.906 (95% CI 0.836–0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1–13.8) and 0.34 (95% CI 0.26–0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value. PMID:27373718

  3. Mycobacteriosis in ostriches (Struthio camelus) due to infection with Mycobacterium bovis and Mycobacterium avium complex.

    PubMed

    Kelly, Pamela; Jahns, Hanne; Power, Eugene; Bainbridge, John; Kenny, Kevin; Corpa, Juan M; Cassidy, Joseph P; Callanan, John J

    2013-12-01

    Avian tuberculosis rarely affects ratites compared to other bird species and is typically caused by Mycobacterium avium species. This study describes the pathological and microbiological findings in three adult ostriches with mycobacteriosis, in one of which Mycobacterium bovis was isolated from the lesions. Post mortem examinations on ostriches from two different zoological collections in Ireland revealed multifocal caseous granulomas affecting the spleen and liver in all cases, with additional involvement of intestines in two cases. In one case, granulomas were present within the pharynx, at the thoracic inlet and multifocally on the pleural surface. Acid-fast bacilli were observed in all lesions. Mycobacterium sp. of the M. avium complex was isolated from the intestinal lesions in the two cases with intestinal involvement, and M. bovis sp. oligotype SB0140 was cultured from the liver of the third ostrich. This represents the first reported case of M. bovis infection in an ostrich. Avian tuberculosis due to M. bovis is rare and to date has been reported in only parrots and experimentally inoculated birds. Mycobacterium bovis needs to be considered as a possible cause of tuberculosis in ostriches because the lesions are similar to those observed with M. avium complex infection.

  4. Mycobacterium marseillense sp. nov., Mycobacterium timonense sp. nov. and Mycobacterium bouchedurhonense sp. nov., members of the Mycobacterium avium complex.

    PubMed

    Ben Salah, Iskandar; Cayrou, Caroline; Raoult, Didier; Drancourt, Michel

    2009-11-01

    An rpoB sequence-based evaluation of 100 Mycobacterium avium complex (MAC) clinical isolates led to the identification of five respiratory tract isolates that were potential representatives of three novel MAC species. Distinctive phenotypic features of isolates 62863 and 5356591(T) included a pseudomycelium morphology and both esterase and acid phosphatase activities. These two isolates exhibited sequence similarities of 99.8 % for the 16S rRNA gene, 86.3 and 86.1 % for 16S-23S rRNA gene internal transcribed spacer (ITS-1) sequence, 96.7 and 97.8 % for rpoB and 97.6 and 97.4 % for hsp65, respectively, with the type strain of Mycobacterium chimaera, the most closely related species. Isolates 3256799 and 5351974(T) lacked alpha-mannosidase and beta-glucosidase activities. They exhibited sequence similarities of 99.6 % for the 16S rRNA gene, 90.1 and 90.4 % for ITS-1, 97.8 % for rpoB and 98.0 and 98.1 % for hsp65, respectively, with the type strain of M. chimaera, the most closely related species. Isolate 4355387(T) lacked urease and alpha-glucosidase activities, but it exhibited valine arylamidase, cystine arylamidase and acid phosphatase activities. It had sequence similarities of 99.3 % for the 16S rRNA gene, 51.8 % for ITS-1, 97.1 % for rpoB and 97.8 % for hsp65 with the type strain of Mycobacterium colombiense, the most closely related species. A phylogenetic tree based on concatenated 16S rRNA gene, ITS-1, rpoB and hsp65 sequences showed the uniqueness of these five isolates as representatives of three novel species, with bootstrap values >/=95 % in all nodes. On the basis of these phenotypic and genetic characteristics, these five isolates are proposed as representatives of three novel MAC species: Mycobacterium marseillense sp. nov., with strain 5356591(T) (=CCUG 56325(T) =CIP 109828(T) =CSUR P30(T)) as the type strain; Mycobacterium timonense sp. nov., with strain 5351974(T) (=CCUG 56329(T) =CIP 109830(T) =CSUR P32(T)) as the type strain; and Mycobacterium

  5. Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection

    PubMed Central

    Ablanedo-Terrazas, Yuria; Ormsby, Christopher E.; Reyes-Terán, Gustavo

    2012-01-01

    Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject. PMID:22481952

  6. Identification of two novel Mycobacterium avium allelic variants in pig and human isolates from Brazil by PCR-restriction enzyme analysis.

    PubMed

    Leão, S C; Briones, M R; Sircili, M P; Balian, S C; Mores, N; Ferreira-Neto, J S

    1999-08-01

    Mycobacterium avium complex (MAC) is composed of environmental mycobacteria found widely in soil, water, and aerosols that can cause disease in animals and humans, especially disseminated infections in AIDS patients. MAC consists of two closely related species, M. avium and M. intracellulare, and may also include other, less-defined groups. The precise differentiation of MAC species is a fundamental step in epidemiological studies and for the evaluation of possible reservoirs for MAC infection in humans and animals. In this study, which included 111 pig and 26 clinical MAC isolates, two novel allelic M. avium PCR-restriction enzyme analysis (PRA) variants were identified, differing from the M. avium PRA prototype in the HaeIII digestion pattern. Mutations in HaeIII sites were confirmed by DNA sequencing. Identification of these isolates as M. avium was confirmed by PCR with DT1-DT6 and IS1245 primers, nucleic acid hybridization with the AccuProbe system, 16S ribosomal DNA sequencing, and biochemical tests. The characterization of M. avium PRA variants can be useful in the elucidation of factors involved in mycobacterial virulence and routes of infection and also has diagnostic significance, since they can be misidentified as M. simiae II and M. kansasii I if the PRA method is used in the clinical laboratory for identification of mycobacteria.

  7. Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria.

    PubMed

    Kotilainen, H; Valtonen, V; Tukiainen, P; Poussa, T; Eskola, J; Järvinen, A

    2015-09-01

    We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.

  8. Nutritional indicators are correlated with the radiological severity score in patients with Mycobacterium avium complex pulmonary disease: a cross-sectional study.

    PubMed

    Morimoto, Kozo; Yoshiyama, Takashi; Kurashima, Atsuyuki; Sasaki, Yuka; Hoshino, Yoshihiko; Yoshimori, Kouzou; Ogata, Hideo; Gemma, Akihiko; Kudoh, Shoji; Shiraishi, Yuji

    2014-01-01

    Body weight loss in patients with Mycobacterium avium complex (MAC) pulmonary disease can be fatal. The administration of nutritional supplements should be an important component in the treatment of this disease. Objective data regarding the association between the nutritional status and disease severity have not been reported. This cross-sectional study aimed to compare the nutritional status and radiological severity scores in MAC pulmonary disease patients. We retrospectively reviewed the records of 40 patients who were admitted to our institution for the treatment of MAC pulmonary disease between July 2008 and July 2010. Nutritional indices, including the ideal body weight ratio, triceps skinfold, mid-upper arm muscle circumference, and percentage of predicted resting energy expenditure, were compared with the radiological severity scores. Quantitative values of the extent of nodules, infiltration shadows, cavities, and bronchiectasis on the computed tomography scans were used to evaluate the radiological severity scores. The patients suffered from a significantly decreased percentage of ideal body weight, body fat and muscle mass. The average radiological score was 17.6±8.4 points. The percentage of ideal body weight (p<0.001), percentage of triceps skinfold (p<0.001) and percentage of mid-upper arm muscle circumference (p<0.002) were negatively correlated with the radiological scores, while the percentage of the predicted resting energy expenditure (p<0.001) was positively correlated with the scores. A poor nutritional status is common in patients with progressive MAC pulmonary disease, which supports the hypothesis that aggressive nutritional interventions are indicated in the treatment of this disease.

  9. Impact of cavity and infiltration on pulmonary function and health-related quality of life in pulmonary Mycobacterium avium complex disease: A 3-dimensional computed tomographic analysis.

    PubMed

    Asakura, Takanori; Yamada, Yoshitake; Namkoong, Ho; Suzuki, Shoji; Niijima, Yuki; Kamata, Hirofumi; Funatsu, Yohei; Yagi, Kazuma; Okamori, Satoshi; Sugiura, Hiroaki; Ishii, Makoto; Jinzaki, Masahiro; Betsuyaku, Tomoko; Hasegawa, Naoki

    2017-05-01

    Pulmonary Mycobacterium avium complex (pMAC) disease manifests as various types of lesions, such as infiltrates, nodules, cavities, and bronchiectasis. However, the important determinants for clinical parameters in lung involvement are poorly understood. The objective of this study was to obtain quantitative parameters by 3-dimensional CT, and investigate the relationship between these parameters and the pulmonary function tests (PFTs) and health-related quality of life. Quantitative analysis using CT was performed in 67 pMAC patients. The relationship between new quantitative parameters for evaluating lung involvement using 3-dimensional CT and PFTs or St George's Respiratory Questionnaire (SGRQ) was evaluated. The ratio of infiltration to total lung volume showed significant correlation with the PFT results, especially the percent-predicted forced vital capacity (%FVC; ρ = -0.52), residual volume (ρ = -0.51), and total lung capacity (ρ = -0.59). The cavity volume was strongly correlated with the %FVC (ρ = -0.78) in the cavity group, while the ratio of infiltration to total lung volume was strongly correlated with the %FVC (ρ = -0.53) in the non-cavity group. The ratio of infiltration to total lung volume was significantly correlated with all SGRQ parameters (ρ = 0.41-0.52) in the non-cavity group. Infiltration was an important parameter for the PFTs and SGRQ in pMAC patients according to the 3-dimensional CT analysis. Moreover, cavity volume was an important parameter of the PFTs in the cavity group. Therefore, infiltration and cavity volume are key features for the management of pMAC disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Cell-free system responsible for internal radiolabeling of glycopeptidolipids of the Mycobacterium avium complex.

    PubMed Central

    Ramasesh, N; Wright, E L; Barrow, W W

    1992-01-01

    Internal radiolabeling of serotype-specific glycopeptidolipids with [14C]mannose was accomplished with a cell-free system derived from serotype 20 of the Mycobacterium avium complex. Similar radiolabeling was not apparent with a cell-free system derived from the rough colony variant, previously shown to be devoid of glycopeptidolipids. Although a comparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein analysis of the parent and rough variant strains revealed a close similarity, there were some proteins unique to the parent strain. Images PMID:1729193

  11. Characterization of total deoxyribonucleic acid of Mycobacterium paratuberculosis (ATCC 19698) and of M. avium complex (ATCC 25291) using restriction enzymes.

    PubMed

    Labidi, A

    1988-01-01

    Total DNA was extracted from M. paratuberculosis (ATCC 19698) and from M. avium complex (ATCC 25291) cultivated on RVB-10 enriched liquid media. Restriction endonuclease analysis was conducted of Total DNA using 34 enzymes and DNA digestion profiles were compared. Fifteen enzymes revealed important differences between the two species. Two pairs of enzymes (EcoRII, BstNI) and (MboI, Sau3AI) provide evidence for the presence of dcmI and dam methylation in DNA of M. avium complex and M. paratuberculosis. The differences in DNA fragments of these two species could be of potential value in differentiating these clinically significant mycobacteria.

  12. Disseminated Mycobacterium avium complex infection in a child with partial dominant interferon gamma receptor 1 deficiency in India.

    PubMed

    Sharma, Varun K; Pai, Gautham; Deswarte, Caroline; Lodha, Rakesh; Singh, Sarman; Kang, Liew Woei; Yin, Chong Chia; Casanova, Jean-Laurent; Bustamante, Jacinta; Kabra, Sushil K

    2015-07-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by clinical disease caused by weakly virulent mycobacteria. All genes mutated in MSMD patients are involved in IFN-γ immunity. Autosomal partial dominant (PD) interferon-γ receptor 1 (IFN-γR1) deficiency is the most frequent abnormality affecting the group of MSMD patients leading to impaired response of IFN-γ. We describe here a patient from India with disseminated infection due to Mycobacterium avium intracellulare (MAC) including multifocal osteomyelitis and BCG disease. A heterozygous mutation in exon 6 of IFNGR1 gene was identified, conferring an autosomal PD IFN-γR1 deficiency. Patient had recurrence of mycobacterial disease during antibiotic therapy for which subcutaneous IFN-γ was added as a modality of treatment for resistant MAC infection.

  13. Modified lymphocyte response to mitogens after intraperitoneal injection of glycopeptidolipid antigens from Mycobacterium avium complex.

    PubMed Central

    Brownback, P E; Barrow, W W

    1988-01-01

    Intraperitoneal injection of glycopeptidolipid (GPL) antigens from Mycobacterium avium complex serovar 4 resulted in the decreased ability of murine splenic lymphocytes to respond to nonspecific-mitogen-induced blastogenesis when exposed to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Adherent cell depletion and cell mixing experiments with T lymphocytes indicated that macrophages were not a major contributor to the immunosuppression observed in this study. Enumeration of splenic lymphocytes by means of flow-cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies demonstrated that intraperitoneal injection of GPL antigens resulted in a significant decrease in Thy-1+ and Lyt-1+ cells but no change in the numbers of Lyt-2+ cells. Treatment with GPL antigens in vitro affected the ability of splenic mononuclear cells to respond optimally for concanavalin A-induced blastogenesis at 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml and lipopolysaccharide-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. However, in vitro treatment with GPL antigens did not affect phytohemagglutinin-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. These findings suggest that GPL antigens or their metabolites affect lymphocyte function and may be important cofactors in the overall pathogenesis of M. avium complex infections. PMID:3258582

  14. In vitro activity of amikacin against isolates of Mycobacterium avium complex with proposed MIC breakpoints and finding of a 16S rRNA gene mutation in treated isolates.

    PubMed

    Brown-Elliott, Barbara A; Iakhiaeva, Elena; Griffith, David E; Woods, Gail L; Stout, Jason E; Wolfe, Cameron R; Turenne, Christine Y; Wallace, Richard J

    2013-10-01

    Amikacin is a major drug used for the treatment of Mycobacterium avium complex (MAC) disease, but standard laboratory guidelines for susceptibility testing are not available. This study presents in vitro amikacin MICs for 462 consecutive clinical isolates of the MAC using a broth microdilution assay. Approximately 50% of isolates had amikacin MICs of 8 μg/ml, and 86% had MICs of ≤16 μg/ml. Of the eight isolates (1.7%) with MICs of 64 μg/ml, five had an MIC of 32 μg/ml on repeat testing. Ten isolates (2.1%) had an initial amikacin MIC of >64 μg/ml, of which seven (1.5%) had MICs of >64 μg/ml on repeat testing. These seven isolates had a 16S rRNA gene A1408G mutation and included M. avium, Mycobacterium intracellulare, and Mycobacterium chimaera. Clinical data were available for five of these seven isolates, all of which had received prolonged (>6 months) prior therapy, with four that were known to be treated with amikacin. The 16S mutation was not detected in isolates with MICs of ≤64 μg/ml. We recommend primary testing of amikacin against isolates of the MAC and propose MIC guidelines for breakpoints that are identical to the CLSI guidelines for Mycobacterium abscessus: ≤16 μg/ml for susceptible, 32 μg/ml for intermediate, and ≥64 μg/ml for resistant. If considered and approved by the CLSI, this will be only the second drug recommended for primary susceptibility testing against the MAC and should facilitate its use for both intravenous and inhaled drug therapies.

  15. Culture and molecular method for detection of Mycobacterium tuberculosis complex and Mycobacterium avium subsp. paratuberculosis in milk and dairy products.

    PubMed

    Messelhäusser, U; Kämpf, P; Hörmansdorfer, S; Wagner, B; Schalch, B; Busch, U; Höller, C; Wallner, P; Barth, G; Rampp, A

    2012-01-01

    A combined molecular and cultural method for the detection of the Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium subsp. paratuberculosis was developed and tested with artificially contaminated milk and dairy products. Results indicate that the method can be used for a reliable detection as a basis for first risk assessments.

  16. Pilot Quasi-Randomized Controlled Study of Herbal Medicine Hochuekkito as an Adjunct to Conventional Treatment for Progressed Pulmonary Mycobacterium avium Complex Disease

    PubMed Central

    Enomoto, Yasunori; Hagiwara, Eri; Komatsu, Shigeru; Nishihira, Ryuichi; Baba, Tomohisa; Kitamura, Hideya; Sekine, Akimasa; Nakazawa, Atsuhito; Ogura, Takashi

    2014-01-01

    Introduction Hochuekkito, a traditional herbal medicine, is occasionally prescribed in Japan to treat patients with a poor general condition. We aimed to examine whether this medicine was beneficial and tolerable for patients with progressed pulmonary Mycobacterium avium complex (MAC) disease. Methods This pilot open-label quasi-randomized controlled trial enrolled 18 patients with progressed pulmonary MAC disease who had initiated antimycobacterial treatment over one year ago but were persistently culture-positive or intolerant. All patients continued their baseline treatment regimens with (n = 9) or without (n = 9) oral Hochuekkito for 24 weeks. Results Baseline characteristics were generally similar between the groups. Most patients were elderly (median age 70 years), female, had a low body mass index (<20 kg/m2), and a long-term disease duration (median approximately 8 years). After the 24-week treatment period, no patient achieved sputum conversion. Although the number of colonies in sputum tended to increase in the control group, it generally remained stable in the Hochuekkito group. Radiological disease control was frequently observed in the Hochuekkito group than the control group (8/9 vs. 3/9; p = 0.05). Patients in the Hochuekkito group tended to experience increase in body weight and serum albumin level compared with those in the control group (median body weight change: +0.4 kg vs. −0.8 kg; median albumin change: +0.2 g/dl vs. ±0.0 g/dl). No severe adverse events occurred. Conclusions Hochuekkito could be an effective, feasible adjunct to conventional therapy for patients with progressed pulmonary MAC disease. Future study is needed to explore this possibility. Trial Registration UMIN Clinical Trials Registry UMIN000009920 PMID:25093868

  17. Urinary mycobacterium avium presenting as sterile pyuria

    PubMed Central

    Yang, Kai; Samplaski, Mary; Mazzulli, Tony; Lo, Kirk; Grober, Ethan; Jarvi, Keith Allen

    2016-01-01

    A 65-year-old healthy woman presented with persistent, asymptomatic sterile pyuria detected by her family physician. While she did not have symptoms, the patient recounts that she has had cloudy urine for years. Cultures of the urine for bacteria showed no growth and no fungi were identified. First-morning urine samples were sent for both tuberculosis and nontuberculosis mycobacterium species testing. The culture grew genotypically identified Mycobaterium avium complex (MAC). Mantoux skin testing was positive. No urological abnormalities were detected by ultrasound and computed tomography (CT) imaging of the urinary tract. PMID:27790302

  18. Detection of Mycobacterium tuberculosis and Mycobacterium avium Complexes by Real-Time PCR in Bovine Milk from Brazilian Dairy Farms.

    PubMed

    Bezerra, André Vinícius Andrade; Dos Reis, Emily Marques; Rodrigues, Rogério Oliveira; Cenci, Alexander; Cerva, Cristine; Mayer, Fabiana Quoos

    2015-05-01

    Foodborne diseases are a public health problem worldwide. The consumption of contaminated raw milk has been recognized as a major cause of transmission of bovine tuberculosis to humans. Other mycobacteria that may be present in raw milk and may cause diseases are those belonging to the Mycobacterium avium complex. In this study, molecular biology tools were applied to investigate raw milk contamination with Mycobacterium spp. in family dairy farms from Rio Grande do Sul, southern Brazil. Furthermore, different variables related to the source of the milk, herd characteristics, and management were evaluated for their effect on milk contamination. Five hundred and two samples were analyzed, of which 354 were from the Northwest region (102 farms with samples from 93 bulk tanks and 261 animals) and 148 from the South region of the state (22 farms with samples from 23 bulk tanks and 125 animals). Among them, 10 (1.99%) and 7 (1.39%) were positive for Mycobacterium tuberculosis (9 confirmed as Mycobacterium bovis) and M. avium complexes, respectively. There was no difference in the frequencies of positive samples between the regions or the sample sources. Of the positive samples, 4 were collected from a bulk tank (1 positive for M. avium and 3 for M. tuberculosis). Moreover, 1 sample was positive concomitantly for M. tuberculosis and M. avium complexes. On risk analysis, no variable was associated with raw milk contamination by M. tuberculosis complex species. However, washing the udders of all animals and drying them with paper towels were weakly classified as risk factors for M. avium contamination. Positive samples were obtained from both animals and bulk tanks, which emphasizes the importance of tuberculosis control programs and provides evidence that milk monitoring can be used as a control practice. Moreover, the findings of this study reinforce the need for awareness of the problems of raw milk consumption among the general population.

  19. Clinical Evaluation of COBAS TaqMan PCR for the Detection of Mycobacterium tuberculosis and M. avium Complex

    PubMed Central

    Ikegame, Satoshi; Sakoda, Yoritake; Fujino, Nao; Taguchi, Kazuhito; Kawasaki, Masayuki; Kajiki, Akira

    2012-01-01

    A retrospective observational study was performed to determine the sensitivity and limitation of PCR test for the detection of Mycobacterium tuberculosis and M. avium complex. We obtained clinical specimens collected from the respiratory tract, cultured M. tuberculosis or M. avium complex, and performed PCR analysis. A total of 299 samples (M. tuberculosis, 177; M. avium, 35; M. intracellulare, 87) were analyzed by COBAS TaqMan PCR from April 2007 to March 2011. The PCR positivity rates were 50–55%, 70–100%, 88–98%, and 100% in smear-negative, smear 1+, 2+, and 3+ groups, respectively. The PCR positivity of tuberculosis in smear 1+ was 80.6%, which was statistically significantly (P < 0.001) lower than that of smear 2+ (97.3%). From January 2005 to March 2007, we collected an additional 138 samples (M. tuberculosis, 74; M. avium, 21; M. intracellulare, 43), which were analyzed by COBAS Amplicor PCR. The PCR positivity rates obtained using COBAS TaqMan PCR and COBAS Amplicor PCR were not significantly different. The sensitivity of PCR test for mycobacteria is not sufficient in case of smear 1+. Careful consideration must be given to the interpretation of negative PCR test results in smear 1+, because smear-positive tuberculosis is the criterion for isolation. PMID:23029612

  20. Liposome encapsulation of clofazimine reduces toxicity in vitro and in vivo and improves therapeutic efficacy in the beige mouse model of disseminated Mycobacterium avium-M. intracellulare complex infection.

    PubMed Central

    Mehta, R T

    1996-01-01

    Disseminated infections caused by the Mycobacterium avium-M. intracellulare complex (MAC) are the most frequent opportunistic bacterial infections in patients with AIDS. MAC isolates are resistant to many of the standard antituberculous drugs. Failure to obtain significant activities of certain drugs is due to difficulty in achieving high concentrations at the sites where the infections reside. New and improved agents for the treatment of mycobacterial infections are therefore required. Earlier, the anti-MAC activities of various agents in free or liposomal form were studied; liposomes were used as drug carriers to ultimately target the drugs to macrophages where mycobacterial infections reside. Clofazimine was chosen for further studies because it could be effectively encapsulated and its activity was well maintained in liposomal form. The present studies with both erythrocytes and macrophages as the model systems show that liposomal drug is far less toxic in vitro than the free drug. The in vivo toxicity of clofazimine was also significantly reduced after liposome encapsulation. The therapeutic efficacies of free and liposomal drugs were compared in a beige mouse model of disseminated MAC infection. An equivalent dose of liposomal drug (10 mg/kg of body weight) was more effective in eliminating the bacterial from the various organs studied, particularly from the liver. Moreover, because of the reduced toxicity of liposomal drug, higher doses could be administered, resulting in a significant reduction in the numbers of CFU in the liver, spleen, and kidneys. The data demonstrate that liposomal clofazimine is highly effective in the treatment of MAC infections, even if the treatment is initiated after a disseminated infection has been established. The present studies thus suggest the potential usefulness of liposomal clofazimine for the treatment of disseminated MAC infections. PMID:8843300

  1. Infection of Eurasian badgers (Meles meles) with Mycobacterium bovis and Mycobacterium avium complex in Spain.

    PubMed

    Balseiro, Ana; Rodríguez, Oscar; González-Quirós, Pablo; Merediz, Isabel; Sevilla, Iker A; Davé, Dipesh; Dalley, Deanna J; Lesellier, Sandrine; Chambers, Mark A; Bezos, Javier; Muñoz, Marta; Delahay, Richard J; Gortázar, Christian; Prieto, José M

    2011-11-01

    The prevalence, distribution and pathology related to infection with Mycobacterium bovis and other mycobacteria were determined in trapped (n=36) and road-killed (n=121) badgers in Spain from 2006 to 2010. The prevalence of M. bovis based on bacteriological culture from road-killed badgers was 8/121 (6.6%) and from trapped badgers was 0/36 (0%). Tuberculosis/M. bovis infection was evident in 15/121 (12.4%) road-killed badgers when bacteriology and histopathology were combined. Mycobacterium avium complex was isolated by culture from the tracheal aspirate of 1/36 (2.8%) trapped badgers and from tissue pools from 8/121 (6.6%) road-killed badgers.

  2. Heat inactivation of Mycobacterium avium-Mycobacterium intracellulare complex organisms in meat products.

    PubMed Central

    Merkal, R S; Crawford, J A; Whipple, D L

    1979-01-01

    Wieners and sausages were prepared which contained the most heat-tolerant representative of the Mycobacterium avium-Mycobacterium intracellulare complex we were able to obtain. They also were prepared with infected tissues obtained from tuberculous swine. Processing conditions were as varied as possible. Neither incorporation of sodium nitrite in the emulsion nor presence of smoke during processing altered the heat susceptibility of the organisms. Substantial killing of the organisms occurred as wieners reached the upper processing temperatures, but hot oil or radiant heating of the "precooked" sausages allowed very short times within the killing range; hence, higher peak internal temperatures were necessary. The lethalities for these organisms of reaching and maintaining various processing temperatures are given. PMID:575610

  3. Disseminated Mycobacterium avium complex disease in a patient with left ventricular assist device (Heart Mate II).

    PubMed

    Cordioli, Maddalena; Del Bravo, Paola; Rigo, Fabio; Azzini, Anna Maria; Merighi, Mara; Forni, Alberto; Concia, Ercole

    2015-09-01

    Although disseminated Mycobacterium avium complex disease occurs mainly in immunocompromised hosts, especially HIV-infected patients in the last stage of the disease (AIDS), this condition is still rare in immunocompetent subjects. We report the case of a Caucasian man who received a left ventricular assist device two years before as a bridge to heart transplantation, that began to present signs and symptoms of mycobacterial infection. The diagnostic work-up we performed showed the presence of Mycobacterium intracellulare in lungs and both peripherical and bone marrow blood. Although evaluated, we found no abnormalities in the patient's immune system that can be related to mycobacterial infection. The beginning of a specific therapy made the patient slowly improve and further nuclear medicine assay (PET-TC) showed a good reduction in radio-labelled drug captation.

  4. Mycobacterium avium subspecies paratuberculosis and Mycobacterium avium subsp. avium infections in a tule elk (Cervus elaphus nannodes) herd.

    PubMed

    Crawford, Graham C; Ziccardi, Michael H; Gonzales, Ben J; Woods, Leslie M; Fischer, Jon K; Manning, Elizabeth J B; Mazet, Jonna A K

    2006-10-01

    Between 2 August and 22 September 2000, 37 hunter-killed tule elk (Cervus elaphus nannodes) were evaluated at the Grizzly Island Wildlife Area, California, USA, for evidence of paratuberculosis. Elk were examined post-mortem, and tissue and fecal samples were submitted for radiometric mycobacterial culture. Acid-fast isolates were identified by a multiplex polymerase chain reaction (PCR) that discriminates among members of the Mycobacterium avium complex (MAC). Histopathologic evaluations were completed, and animals were tested for antibodies using a Johne's enzyme-linked immunosorbent assay (ELISA) and agar gel immunodiffusion. In addition, 104 fecal samples from tule elk remaining in the herd were collected from the ground and submitted for radiometric mycobacterial culture. No gross lesions were detected in any of the hunter-killed animals. Mycobacterium avium subsp. paratuberculosis (MAP) was cultured once from ileocecal tissue of one adult elk and was determined to be a strain (A18) found commonly in infected cattle. One or more isolates of Mycobacterium avium subsp. avium (MAA) were isolated from tissues of five additional adult elk. Gastrointestinal tract and lymph node tissues from 17 of the 37 elk (46%) examined had histopathologic lesions commonly seen with mycobacterial infection; however, acid-fast bacteria were not observed. All MAC infections were detected from adult elk (P = 0.023). In adult elk, a statistically significant association was found between MAA infection and ELISA sample-to-positive ratio (S/P) > or = 0.25 (P=0.021); four of five MAA culture-positive elk tested positive by ELISA. Sensitivity and specificity of ELISA S/P > or = 0.25 for detection of MAA in adult elk were 50% and 93%, respectively. No significant associations were found between MAC infection and sex or histopathologic lesions. Bacteriologic culture confirmed infection with MAP and MAA in this asymptomatic tule elk herd. The Johne's ELISA was useful in signaling

  5. Identification of Mycobacterium avium and Mycobacterium intracellulare isolated in Puerto Rico from clinical samples by the use of a non-radioactive DNA probe.

    PubMed

    García, M T; Peña, I; Zlotnik, H

    1994-06-01

    The Mycobacterium avium complex (MAC), especially M. avium, is an important opportunistic pathogen of AIDS patients in the United States. In Puerto Rico, the incidence of infections caused by MAC has not been determined. This is due, in part, to the difficulties associated to the microbiological identification of the microorganisms. In this work, a commercially available kit (AccuProbe, Gen-Probe, Inc., San Diego, CA) utilizing a DNA probe complementary to rRNA of M. avium and M. intracellulare was used to identify seventeen MAC strains and one unknown atypical mycobacterium recovered in culture in Puerto Rico from clinical samples. The results obtained revealed that M. avium was the predominant species recovered (83% of isolates tested). Only two cultures were identified as M. intracellulare. The unknown culture, which did not react with either probe, turned out to be M. gordonae. The probe tests not only are simple to perform, but provide cultural identification results in as little as two hours. This study, the first one of its kind in Puerto Rico, demonstrates that the nucleic acid probes for the cultural identification of M. avium and M. intracellulare offer the potential of providing a prompt diagnosis and much needed data on the epidemiology of MAC infections in Puerto Rico.

  6. The clinical efficacy of a clarithromycin-based regimen for Mycobacterium avium complex disease: A nationwide post-marketing study.

    PubMed

    Kadota, Jun-Ichi; Kurashima, Atsuyuki; Suzuki, Katsuhiro

    2017-05-01

    The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates.

    PubMed

    Hirama, Takashi; Shiono, Ayako; Egashira, Hiroshi; Kishi, Etsuko; Hagiwara, Koichi; Nakamura, Hidetoshi; Kanazawa, Minoru; Nagata, Makoto

    2016-03-01

    The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. The pncA gene from naturally pyrazinamide-resistant Mycobacterium avium encodes pyrazinamidase and confers pyrazinamide susceptibility to resistant M. tuberculosis complex organisms.

    PubMed

    Sun, Z; Scorpio, A; Zhang, Y

    1997-10-01

    The antituberculosis drug pyrazinamide (PZA) needs to be converted into pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) in order to show bactericidal activity against Mycobacterium tuberculosis. M. avium is naturally resistant to PZA. To investigate whether this natural resistance to PZA is due to inability of the M. avium PZase to convert PZA to bactericidal POA, the M. avium PZase gene (pncA) was cloned by using the M. tuberculosis pncA gene as a probe. Sequence analysis showed that the M. avium pncA gene is 561 bp long, encoding a protein with a predicted size of about 19.8 kDa; but Western blotting showed that the M. avium PZase migrated as a 24 kDa band when expressed in M. bovis BCG and Escherichia coli. Sequence comparison revealed that M. avium PZase has 67.7% and 32.8% amino acid identity with the corresponding enzymes from M. tuberculosis and E. coli, respectively. Southern blot analysis with the M. avium pncA gene as a probe showed that M. terrae, M. gastri, M. marinum, M. fortuitum, M. xenopi, M. gordonae, M. szulgai, M. celatum and M. kansasii have close pncA homologues, whereas M. chelonae and M. smegmatis did not give significant hybridization signals. Transformation with the M. avium pncA gene conferred PZA susceptibility to PZA-resistant M. tuberculosis complex organisms, indicating that the nonsusceptibility of M. avium to PZA is not due to an ineffective PZase enzyme, but appears to be related to other factors such as transport of POA.

  9. Characterization of a Novel Plasmid, pMAH135, from Mycobacterium avium Subsp. hominissuis

    PubMed Central

    Uchiya, Kei-ichi; Takahashi, Hiroyasu; Nakagawa, Taku; Yagi, Tetsuya; Moriyama, Makoto; Inagaki, Takayuki; Ichikawa, Kazuya; Nikai, Toshiaki; Ogawa, Kenji

    2015-01-01

    Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium’s pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection. PMID:25671431

  10. Detection of Mycobacteria, Mycobacterium avium Subspecies, and Mycobacterium tuberculosis Complex by a Novel Tetraplex Real-Time PCR Assay

    PubMed Central

    Molina, Elena; Elguezabal, Natalia; Pérez, Valentín; Garrido, Joseba M.

    2015-01-01

    Mycobacterium tuberculosis complex, Mycobacterium avium, and many other nontuberculous mycobacteria are worldwide distributed microorganisms of major medical and veterinary importance. Considering the growing epidemiologic significance of wildlife-livestock-human interrelation, developing rapid detection tools of high specificity and sensitivity is vital to assess their presence and accelerate the process of diagnosing mycobacteriosis. Here we describe the development and evaluation of a novel tetraplex real-time PCR for simultaneous detection of Mycobacterium genus, M. avium subspecies, and M. tuberculosis complex in an internally monitored single assay. The method was evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28) strains, tissues spiked with different CFU amounts of three mycobacterial species (n = 57), archival clinical samples (n = 233), and strains isolated from various hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M. bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked samples were analyzed, the method consistently detected as few as 100 to 1,000 mycobacterial CFU per gram. The sensitivity and specificity values for the panel of clinical samples were 97.5 and 100% using a verified culture-based method as the reference method. The assays performed on clinical isolates confirmed these results. This PCR was able to identify M. avium and M. tuberculosis complex in the same sample in one reaction. In conclusion, the tetraplex real-time PCR we designed represents a highly specific and sensitive tool for the detection and identification of mycobacteria in routine laboratory diagnosis with potential additional uses. PMID:25588660

  11. Detection of mycobacteria, Mycobacterium avium subspecies, and Mycobacterium tuberculosis complex by a novel tetraplex real-time PCR assay.

    PubMed

    Sevilla, Iker A; Molina, Elena; Elguezabal, Natalia; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A

    2015-03-01

    Mycobacterium tuberculosis complex, Mycobacterium avium, and many other nontuberculous mycobacteria are worldwide distributed microorganisms of major medical and veterinary importance. Considering the growing epidemiologic significance of wildlife-livestock-human interrelation, developing rapid detection tools of high specificity and sensitivity is vital to assess their presence and accelerate the process of diagnosing mycobacteriosis. Here we describe the development and evaluation of a novel tetraplex real-time PCR for simultaneous detection of Mycobacterium genus, M. avium subspecies, and M. tuberculosis complex in an internally monitored single assay. The method was evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28) strains, tissues spiked with different CFU amounts of three mycobacterial species (n = 57), archival clinical samples (n = 233), and strains isolated from various hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M. bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked samples were analyzed, the method consistently detected as few as 100 to 1,000 mycobacterial CFU per gram. The sensitivity and specificity values for the panel of clinical samples were 97.5 and 100% using a verified culture-based method as the reference method. The assays performed on clinical isolates confirmed these results. This PCR was able to identify M. avium and M. tuberculosis complex in the same sample in one reaction. In conclusion, the tetraplex real-time PCR we designed represents a highly specific and sensitive tool for the detection and identification of mycobacteria in routine laboratory diagnosis with potential additional uses.

  12. Diversity of Mycobacterium avium subsp. hominissuis mycobacteria causing lymphadenitis, France.

    PubMed

    Despierres, L; Cohen-Bacrie, S; Richet, H; Drancourt, M

    2012-07-01

    The knowledge of Mycobacterium avium complex (MAC) genotypes responsible for lymphadenitis is limited. We retrospectively characterized all of the MAC isolates made in our laboratory in the last 18 years by sequence-based identification and genotyping, and compared the clinical and laboratory data for lymphadenitis-associated and non-lymphadenitis-associated MAC isolates. Of 67 MAC-infected patients, 25 lymphadenitis patients were significantly younger than 42 non-lymphadenitis patients, while the male/female ratio did not significantly differ between the two groups. Cervical topography found in 76.5% of lymphadenitis patients was significantly more frequent in non-immunocompromised patients (p=0.04). M. avium subsp. hominissuis was identified in 53 patients (24 lymphadenitis, 29 non-lymphadenitis), M. colombiense in six patients (five non-lymphadenitis, one lymphadenitis), M. intracellulare in four non-lymphadenitis patients, and M. chimaera in three non-lymphadenitis patients, while negative controls remained negative. M. hominissuis was significantly associated with lymphadenitis (p=0.03). M. hominissuis isolates yielded 15 genotypes in 29 non-lymphadenitis isolates (molecular diversity, 0.622) versus 11 genotypes in 24 lymphadenitis isolates (molecular diversity, 0.578), demonstrating a non-significant lower diversity of M. hominissuis isolates cultured from lymphadenitis. The genotypes did not correlate with the clinical features. These data suggest the presence of several environmental reservoirs for M. hominissuis causing lymphadenitis in France.

  13. The relationship of temperature to desiccation and starvation tolerance of the Mycobacterium avium complex.

    PubMed

    Archuleta, Rebecca Joy; Mullens, Patricia; Primm, Todd P

    2002-10-01

    Mycobacterium avium grew in media at 14-37 degrees C, and persisted at 4 degrees C and 42 degrees C. The bacteria lost approximately 90% viability after 3 months in reverse-osmosis deionized water at 4-37 degrees C. Cooler temperatures lowered the death rate. Death rates also decreased after a 5- to 10-day starvation adaptation period. Alterations of the steady-state levels of different mycolic acid classes, presumably to facilitate thermoadaptation, were found. Following desiccation, M. avium lost viability at a constant rate (half-life of 2.3 days). This implies that bacilli contaminating dry medical surfaces would persist for short periods of time. The remarkable stress survival exhibited by M. avium further suggests persistence in a range of environmental and clinical settings.

  14. Molecular characterization and drug susceptibility profile of a Mycobacterium avium subspecies avium isolate from a dog with disseminated infection.

    PubMed

    Armas, Federica; Furlanello, Tommaso; Camperio, Cristina; Trotta, Michele; Novari, Gianluca; Marianelli, Cinzia

    2016-01-12

    Mycobacterium avium complex (MAC) infections have been described in many mammalian species including humans and pets. We isolated and molecularly typed the causative agent of a rare case of disseminated mycobacteriosis in a dog. We identified the pathogen as a M. avium subspecies avium by sequencing the partial genes gyrB and rpsA. Considering the zoonotic potential of this infection, and in an attempt to ensure the most effective treatment for the animal, we also determined the drug susceptibility profile of the isolate to the most common drugs used to treat MAC disease in humans. The pathogen was tested in vitro against the macrolide clarithromycin, as well as against amikacin, ciprofloxacin, rifampicin, ethambutol and linezolid by the resazurin microdilution assay. It was found to be sensitive to all tested drugs save ethambutol. Despite the fact that the pathogen was sensitive to the therapies administered, the dog's overall clinical status worsened, and the animal died shortly after antimicrobial susceptibility results became available. Nucleotide sequencing of the embB gene, the target gene most commonly associated with ethambutol resistance, showed new missense mutations when compared to sequences available in public databases. In conclusion, we molecularly identified the MAC pathogen and determined its drug susceptibility profile in a relatively short period of time (seven days). We also characterized new genetic mutations likely to have been involved in the observed ethambutol resistance. Our results confirm the usefulness of both the gyrB and the rpsA genes as biomarkers for an accurate identification and differentiation of MAC pathogens.

  15. Specific amplification of gene encoding N-terminal region of catalase-peroxidase protein (KatG-N) for diagnosis of disseminated MAC disease in HIV patients.

    PubMed

    Latawa, Romica; Singh, Krishna Kumar; Wanchu, Ajay; Sethi, Sunil; Sharma, Kusum; Sharma, Aman; Laal, Suman; Verma, Indu

    2014-10-01

    Disseminated Mycobacterium avium-intracellulare complex (MAC) infection is considered as severe complication of advanced HIV/AIDS disease. Currently available various laboratory investigations have not only limited ability to discriminate between MAC infection and tuberculosis but are also laborious and time consuming. The aim of this study was, therefore, to design a molecular-based strategy for specific detection of MAC and its differentiation from Mycobacterium tuberculosis (M. tb) isolated from the blood specimens of HIV patients. A simple PCR was developed based on the amplification of 120-bp katG-N gene corresponding to the first 40 amino acids of N-terminal catalase-peroxidase (KatG) protein of Mycobacterium avium that shows only ~13% sequence homology by clustal W alignment to N-terminal region of M. tb KatG protein. This assay allowed the accurate and rapid detection of MAC bacteremia, distinguishing it from M. tb in a single PCR reaction without any need for sequencing or hybridization protocol to be performed thereafter. This study produced enough evidence that a significant proportion of Indian HIV patients have disseminated MAC bacteremia, suggesting the utility of M. avium katG-N gene PCR for early detection of MAC disease in HIV patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Isolation and identification of Mycobacterium avium complex and other nontuberculosis mycobacteria from drinking-water in Basra governorate, Iraq.

    PubMed

    Al-Sulami, A A; Al-Taee, A M R; Wida'a, Q H

    2012-03-01

    This study aimed to determine the occurrence of Mycobacterium avium complex and other nontuberculous mycobacteria in drinking-water in Basra governorate, Iraq and their susceptibility to several antibiotics and the effect of 0.5 mg/L of chlorine on their survival. A total of 404 samples of drinking-water were collected from 33 different districts of the governorate from November 2006 to August 2007. Filtered samples were incubated for 7 days or less in a monophasic-biphasic culture setup of tuberculosis broth and Lowenstein-Jensen agar. The 252 isolates were identified as M. avium complex (21), M. marinum (15), M. kansasii (30), M. simiae (20), M. szulgai (19), M. xenopi (16), M. malmoense (11), M. fortuitum (37), M. chelonae (50) and M. abscessus (33). Isolates were tested for antibiotic susceptibility as well as their ability to tolerate chlorine at a concentration of 0.5 mg/L. The presence of these pathogenic bacteria in drinking-water renders the water unfit for human consumption.

  17. Polymerase chain reaction-restriction fragment length polymorphism of the rpoB gene for identification of Mycobacterium avium subsp. paratuberculosis and differentiation of Mycobacterium avium subspecies.

    PubMed

    Whang, Jake; Lee, Byung Soo; Choi, Go-Eun; Cho, Sang-Nae; Kil, Park Young; Collins, Michael T; Shin, Sung Jae

    2011-05-01

    Mycobacterial speciation by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) of the rpoB gene was evaluated for identification of Mycobacterium avium subsp. paratuberculosis (MAP) and other Mycobacterium avium complex (MAC) members to the species or subspecies level by comparison with conventional methods including hsp65 sequencing, high-performance liquid chromatography, and PCR for accepted species- or subspecies-specific genomic targets. A total of 185 type and clinical mycobacterial strains from humans, animals, and environments were tested. A 360-bp PCR product was subsequently digested with MspI, HaeIII, and SmaI restriction enzymes. The PRA using SmaI restriction showed a unique digestion pattern for MAP distinguishing it from other MAC members and other Mycobacterium spp. Moreover, HaeIII and MspI restriction of the rpoB gene enabled MAC-species and -subspecies discrimination. The rpoB-PRA using SmaI or MspI and HaeIII restriction of the rpoB gene is a simple, convenient, and reliable confirmatory assay for simultaneous identification of MAP and other MAC members.

  18. Isolation of the Mycobacterium avium-M. intracellulare-M. scrofulaceum complex from tank water in Queensland, Australia.

    PubMed Central

    Tuffley, R E; Holbeche, J D

    1980-01-01

    Disease-associated serotypes of Mycobacterium intracellulare and M. avium have been isolated from 32 of 141 rainwater tanks situated in the basin of the Fitzroy River and its tributaries in central Queensland, 7 of 32 tanks situated in the hinterland of the coastal city of Rockhampton, and 2 of 32 tanks sampled repetitively in the southeastern Queensland city of Toowoomba. M. gordonae was also isolated from 23 of the river basin tanks, from 9 in the Rockhampton hinterland, and from 5 in the city of Toowoomba. One half of these isolates came from tanks which also yielded M. intracellulare. Mycobacteria of the M. terrae-M. triviale-M. nonchromogenicum complex were found in 7 tanks, usually in conjunction with M. intracellulare. The humans who consume the contaminated tank water are free of symptoms but have not been medically examined. It is suggested that mycobacteria adhering to dust particles disturbed by mechanical cultivation may be the source of contamination. PMID:7356321

  19. The presence of opportunistic pathogens, Legionella spp., L. pneumophila and Mycobacterium avium complex, in South Australian reuse water distribution pipelines.

    PubMed

    Whiley, H; Keegan, A; Fallowfield, H; Bentham, R

    2015-06-01

    Water reuse has become increasingly important for sustainable water management. Currently, its application is primarily constrained by the potential health risks. Presently there is limited knowledge regarding the presence and fate of opportunistic pathogens along reuse water distribution pipelines. In this study opportunistic human pathogens Legionella spp., L. pneumophila and Mycobacterium avium complex were detected using real-time polymerase chain reaction along two South Australian reuse water distribution pipelines at maximum concentrations of 10⁵, 10³ and 10⁵ copies/mL, respectively. During the summer period of sampling the concentration of all three organisms significantly increased (P < 0.05) along the pipeline, suggesting multiplication and hence viability. No seasonality in the decrease in chlorine residual along the pipelines was observed. This suggests that the combination of reduced chlorine residual and increased water temperature promoted the presence of these opportunistic pathogens.

  20. [CHANGES IN MAC ANTIBODY LEVELS BEFORE AND AFTER SURGERY AND AT THE TIME OF RELAPSE/RECURRENCE IN MAC LUNG DISEASE--Can MAC Antibodies Be an Indicator of Postoperative Relapse/Recurrence?].

    PubMed

    Yamada, Katsuo; Kawasumi, Yuuta; Yasuda, Ayuko; Seki, Yukio; Adachi, Takashi; Tarumi, Osamu; Hayashi, Yuuta; Nakagawa, Taku; Yamada, Noritaka; Ogawa, Kenji

    2016-02-01

    Patients receiving surgical treatment for Mycobacterium avium complex (MAC), lung disease should be followed up with careful attention paid to relapse/recurrence, but there is some debate regarding the findings based on which relapse/recurrence should be diagnosed. We hypothesized that we might be able to use anti-GPL core IgA antibodies (MAC antibodies), which have been attracting attention as a factor that may support diagnosis of MAC lung disease, to diagnose postoperative relapse/recurrence. Therefore, we compared the levels of these antibodies before and at the time of relapse/recurrence, and also compared antibody titers before and after surgery. MAC antibody titers were elevated by an average of about 50% at the time of relapse/recurrence compared to those before relapse/recurrence for 6 patients. In contrast, MAC antibody titers were about 30% lower after surgery compared to those before surgery for 37 patients. It may be possible to use MAC antibodies as an indicator of postoperative relapse/recurrence for MAC lung disease.

  1. Bordetella avium

    USDA-ARS?s Scientific Manuscript database

    Bordetellosis is an acute, highly contagious disease of the upper respiratory tract of young turkeys (4-8 wk of age). The disease is caused by a gram-negative, nonfermentative bacterium, Bordetella avium. Members of the genus Bordetella are well known for their ability to colonize and damage ciliate...

  2. Clarithromycin Susceptibility Testing of Mycobacterium avium Complex Using 2,3-Diphenyl-5-thienyl-(2)-tetrazolium Chloride Microplate Assay with Middlebrook 7H9 Broth

    PubMed Central

    Park, Young Kil; Koh, Won-Jung; Kim, Shin Ok; Shin, Sonya; Kim, Bum Joon; Cho, Sang-Nae; Lee, Sun Min

    2009-01-01

    A series of 119 Mycobacterium avium complex isolates were subjected to clarithromycin susceptibility testing using microplates containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC). Among 119 isolates, 114 (95.8%) were susceptible to clarithromycin and 5 were resistant according to the new and the standard method. STC counts the low cost and reduces the number of procedures needed for susceptibility testing. PMID:19543518

  3. Early bactericidal activity of rifabutin versus that of placebo in treatment of disseminated Mycobacterium avium complex bacteremia in AIDS patients.

    PubMed Central

    Dautzenberg, B; Castellani, P; Pellegrin, J L; Vittecoq, D; Truffot-Pernot, C; Pirotta, N; Sassella, D

    1996-01-01

    Rifabutin, 600 mg/day, was compared with a placebo in the early treatment of culture-proven Mycobacterium avium bacteremia in patients with AIDS. Following 14 days' treatment, bacteriological success, defined as a negative culture or a reduction in the number of CFU of M. avium organisms per milliliter of blood by a factor of > or = 0.5 log from the baseline, was observed in 7 of 10 (70%) evaluable rifabutin patients and in 1 of 13 (8%) evaluable placebo patients (P = 0.002). Rifabutin is active against M. avium as a single agent and can make a significant contribution to combination regimens for the treatment of disseminated M. avium infection in AIDS patients. PMID:8807071

  4. Loop-Mediated Isothermal Amplification for Direct Detection of Mycobacterium tuberculosis Complex, M. avium, and M. intracellulare in Sputum Samples

    PubMed Central

    Iwamoto, Tomotada; Sonobe, Toshiaki; Hayashi, Kozaburo

    2003-01-01

    Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method in which reagents react under isothermal conditions with high specificity, efficiency, and rapidity. We used LAMP for detection of Mycobacterium tuberculosis complex, Mycobacterium avium, and Mycobacterium intracellulare directly from sputum specimens as well as for detection of culture isolates grown in a liquid medium (MGIT; Nippon Becton Dickinson Co., Ltd., Tokyo, Japan) or on a solid medium (Ogawa's medium). Species-specific primers were designed by targeting the gyrB gene, and their specificities were validated on 24 mycobacterial species and 7 nonmycobacterial species. The whole procedure is quite simple, starting with the mixing of all reagents in a single tube, followed by an isothermal reaction during which the reaction mixture is held at 63°C. The resulting amplicons are visualized by adding SYBR Green I to the reaction tube. The only equipment needed for the amplification reaction is a regular laboratory water bath or heat block that furnishes a constant temperature of 63°C. The assay had a detection limit of 5 to 50 copies of purified DNA with a 60-min incubation time. The reaction time could be shortened to 35 min for the species identification of M. tuberculosis complex, M. avium, and M. intracellulare from a solid-medium culture. Residual DNA lysates prepared for the Amplicor assay (Roche Diagnostics GmbH) from 66 sputum specimens were tested in the LAMP assay. Although the sample size used for the latter assay was small, 2.75 μl of the DNA lysates, it showed a performance comparable with that of the Amplicor assay, which required 50 μl of the lysates. This LAMP-based assay is simple, rapid, and sensitive; a result is available in 35 min for a solid-medium culture and in 60 min for a liquid-medium culture or for a sputum specimen that contains a corresponding amount of DNA available for testing. PMID:12791888

  5. Dynamics of toxic genotypes of Microcystis aeruginosa complex (MAC) through a wide freshwater to marine environmental gradient.

    PubMed

    Martínez de la Escalera, Gabriela; Kruk, Carla; Segura, Angel M; Nogueira, Lucía; Alcántara, Ignacio; Piccini, Claudia

    2017-02-01

    Bloom-forming species belonging to Microcystis aeruginosa complex (MAC) are the most commonly reported worldwide. MAC blooms are composed by toxic and non-toxic genotypes and the environmental conditions favouring the dominance of toxic genotypes are still a matter of debate among the scientific community. In this study, we evaluated the distribution of toxic MAC genotypes along a seasonal cycle and over an environmental gradient spanning 800km, from a eutrophic freshwater reservoir in Río Uruguay to marine water in the outer limit of Río de la Plata. Abundance of four mcy genes, mcyB, mcyD, mcyE and mcyJ was determined by qPCR and used as a proxy of abundance of toxic MAC genotypes. All the mcy genes were detected through the seasonal cycle at all sampling sites, being systematically higher in the freshwater reservoir and decreasing towards the marine site. The highest toxic genotype abundance was found during the austral summer months. According to generalized linear regressions and random forest models, temperature and conductivity were the most relevant explanatory variables. This suggests that although toxic MAC genotypes grow optimally in freshwater, they are also able to tolerate the high-salinity and low temperature conditions found in estuarine and marine waters. This ability to resist harsh conditions impose a health risk and a management challenge. To our knowledge, this is the first report addressing several mcy genes in a broad gradient that includes a wide array of different environmental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Validation of a Multiplex Real-Time PCR Assay for Detection of Mycobacterium spp., Mycobacterium tuberculosis Complex, and Mycobacterium avium Complex Directly from Clinical Samples by Use of the BD Max Open System.

    PubMed

    Rocchetti, Talita T; Silbert, Suzane; Gostnell, Alicia; Kubasek, Carly; Widen, Raymond

    2016-06-01

    A multiplex real-time PCR was validated on the BD Max open system to detect different Mycobacterium tuberculosis complex, Mycobacterium avium complex, and Mycobacterium spp. directly from clinical samples. The PCR results were compared to those with traditional cultures. The multiplex PCR assay was found to be a specific and sensitive method for the rapid detection of mycobacteria directly from clinical specimens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Planning for MacArthur: Harnessing the Complexity of Postwar Japan

    DTIC Science & Technology

    2014-05-22

    Caesar (Boston: Little, Brown, and Company, 1978). 24Robert Eichelberger and Milton Mackaye, Our Jungle Road to Tokyo (Washington, DC: Zenger...descriptive language , Policy 150 outlined nine major points for MacArthur’s staff to consider with respect to economic conditions. It also gave the Chiefs...should” language , Directive 1380/15 outlined General Headquarters’ economic policies with “you will” type language .80 The same polices outlined in

  8. Environmental Assessment for Construction at US Central Command Headquarters Complex MacDill AFB, Florida

    DTIC Science & Technology

    2005-12-01

    organic solvents, chlorine, freon, paints, thinners, oils, lubricants, compressed gases, pesticides , herbicides, nitrates, and chromates. A detailed...of the existing USCENTCOM facility. This alternative would not alter the potential for loss or damage resulting from floods or increase the impacts...MacDill AFB. Envir . Management. Base Historic Pres. Officer NEGATIVE NUMBERS: Roll: 2/Frames: 29; Roll: 3/Frames: 24-25 P H 0 T 0 G R A P H I I ~J

  9. Mycobacterium avium complex olecranon bursitis resolves without antimicrobials or surgical intervention: A case report and review of the literature

    PubMed Central

    Working, Selene; Tyser, Andrew; Levy, Dana

    2015-01-01

    Introduction Nontuberculous mycobacteria are an uncommon cause of septic olecranon bursitis, though cases have increasingly been described in both immunocompromised and immunocompetent hosts. Guidelines recommend a combination of surgical resection and antimicrobials for treatment. This case is the first reported case of nontuberculous mycobacterial olecranon bursitis that resolved without medical or surgical intervention. Case presentation A 67-year-old female developed a painless, fluctuant swelling of the olecranon bursa following blunt trauma to the elbow. Due to persistent bursal swelling, she underwent three separate therapeutic bursal aspirations, two involving intrabursal steroid injection. After the third aspiration, the bursa became erythematous and severely swollen, and bursal fluid grew Mycobacterium avium complex. Triple-drug antimycobacterial therapy was initiated, but discontinued abruptly due to a rash. Surgery was not performed. The patient was observed off antimicrobials, and gradually clinically improved with a compressive dressing. By 14 months after initial presentation, clinical exam revealed complete resolution of the previously erythematous bursal mass. Discussion This is the first reported case of nontuberculous mycobacterial olecranon bursitis managed successfully without surgery or antimicrobials. Musculoskeletal nontuberculous mycobacterial infections are challenging given the lack of clinical data about optimal duration and choice of antimicrobials or the role of surgery. Additionally, the potential toxicity and drug interactions of antimycobacterials are not insignificant and warrant close monitoring if treatment is pursued. Conclusion This case raises an important clinical question of whether close observation off antimicrobials is appropriate in select cases of immunocompetent patients with localized atypical mycobacterial disease of soft tissue and skeletal structures. PMID:26793457

  10. Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

    PubMed Central

    Perronne, C; Gikas, A; Truffot-Pernot, C; Grosset, J; Vilde, J L; Pocidalo, J J

    1991-01-01

    The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection. PMID:1656860

  11. Discovery of tMAC: a Drosophila testis-specific meiotic arrest complex paralogous to Myb–Muv B

    PubMed Central

    Beall, Eileen L.; Lewis, Peter W.; Bell, Maren; Rocha, Michael; Jones, D. Leanne; Botchan, Michael R.

    2007-01-01

    The Drosophila Myb–Muv B (MMB)/dREAM complex regulates gene expression and DNA replication site-specifically, but its activities in vivo have not been thoroughly explored. In ovarian amplification-stage follicle cell nuclei, the largest subunit, Mip130, is a negative regulator of replication, whereas another subunit, Myb, is a positive regulator. Here, we identified a mutation in mip40 and generated a mutation in mip120, two additional MMB subunits. Both mutants were viable, but mip120 mutants had many complex phenotypes including shortened longevity and severe eye defects. mip40 mutant females had severely reduced fertility, whereas mip120 mutant females were sterile, substantiating ovarian regulatory role(s) for MMB. Myb accumulation and binding to polytene chromosomes was dependent on the core factors of the MMB complex. In contrast to the documented mip130 mutant phenotypes, both mip40 and mip120 mutant males were sterile. We purified Mip40-containing complexes from testis nuclear extracts and identified tMAC, a new testis-specific meiotic arrest complex that contained Mip40, Caf1/p55, the Mip130 family member, Always early (Aly), and a Mip120 family member, Tombola (Tomb). Together, these data demonstrate that MMB serves diverse roles in different developmental pathways, and members of MMB can be found in alternative, noninteracting complexes in different cell types. PMID:17403774

  12. Use of restriction fragment length polymorphisms resolved by pulsed-field gel electrophoresis for subspecies identification of mycobacteria in the Mycobacterium avium complex and for isolation of DNA probes.

    PubMed Central

    Coffin, J W; Condon, C; Compston, C A; Potter, K N; Lamontagne, L R; Shafiq, J; Kunimoto, D Y

    1992-01-01

    Mycobacterial strains from the Mycobacterium avium complex were compared with each other and with Mycobacterium phlei isolates by restriction endonuclease digestion of chromosomal DNA with SspI and analysis by pulsed-field gel electrophoresis. Characteristic profiles were observed for known typed strains, and five groups were identified. Primary bovine isolates identified as Mycobacterium paratuberculosis by classical methods were shown to fall into both the M. paratuberculosis- and M. avium-like groups. M. paratuberculosis 18 was in the latter category. Two Mycobacterium intracellulare strains of different Schaefer serotypes had different digestion profiles. In addition, this system was exploited for the preparation of DNA probes by the isolation, digestion, and subcloning of DNA fragments separated by pulsed-field gel electrophoresis. Probe JC12 hybridized only to M. avium complex strains, but not to M. phlei, showing characteristic hybridization profiles for each of the groups previously identified by pulsed-field gel electrophoresis. The approach taken in the study lends itself to the comparative analysis of members of the M. avium complex and to the isolation and characterization of DNA probes with specificity for these mycobacteria. Images PMID:1352787

  13. Antigenicity in sheep of synthetic peptides derived from stress-regulated Mycobacterium avium subsp. paratuberculosis proteins and comparison with recombinant protein and complex native antigens.

    PubMed

    Gurung, Ratna B; Begg, Douglas J; Purdie, Auriol C; Whittington, Richard J

    2014-03-15

    Serum antibody enzyme-linked immunosorbent assay is the most commonly used test for diagnosis of Mycobacterium avium subsp. paratuberculosis infection in ruminants. However, the assay requires serum preabsorption with Mycobacterium phlei proteins to reduce cross reactions potentially contributed by the exposure of livestock to environmental mycobacteria. To trial the discovery of novel antigens which do not require serum absorption, synthetic MAP-specific peptides were selected based on in silico research to identify putative B cell epitopes. Four peptides from previously identified stress-regulated proteins were synthesized and evaluated using enzyme linked immunosorbent assay to detect Mycobacterium avium subsp. paratuberculosis specific antibodies in sheep. Two peptides were from hypothetical MAP proteins (MAP3567 and MAP1168c) and two were from proteins with known function (MAP2698c, an acyl-acyl carrier protein desaturase-DesA2 and MAP2487c a carbonic anhydrase). The ability of each peptide to discriminate between unexposed and MAP exposed (infected and vaccinated) animals was similar to that of the parent recombinant MAP antigen, with area under receiver operating curve values of 0.86-0.93. Assays run with a combination of two peptides showed slightly higher reactivity than those of individual peptides. Peptides evaluated in this study had diagnostic potential similar to corresponding recombinant proteins but not superior to a complex native MAP antigen or a commercial assay. Further study is required to investigate other peptides for their diagnostic potential, and this may be simpler and cheaper than subunit protein-based research. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Drug susceptibility testing of Mycobacterium Avium subsp. Avium isolates from naturally infected domestic pigeons to avian tuberculosis.

    PubMed

    Parvandar, Kaveh; Mayahi, Mansour; Mosavari, Nader; Pajoohi, Reza Aref

    2016-12-01

    Avian tuberculosis is one of the most important infections affecting most species of birds. Several mycobacterial species have been identified causing avian tuberculosis, and the organisms confirmed most frequently are Mycobacterium avium and Mycobacterium genavense. Any species of birds can be infected with M. avium. Generally, domesticated fowl or captive wild birds are affected more frequently than those living in the wild. M. avium can not only infect all species of birds, but can also infect some domesticated mammals to cause disease, usually with localized lesion. In immunocompetent individuals, M. avium complex isolates produce localized soft tissue infections, including chronic pulmonary infections in the elderly and cervical lymphadenitis in children, but rarely any disseminated disease. In patients infected with HIV and AIDS or in other immunocompromised individuals, M. avium complex isolates frequently cause severe systemic infections. The importance of avian tuberculosis and the risk of its zoonotic spread motivated our interest to determine the drug susceptibility testing of M. avium subsp. avium isolates from naturally infected domestic pigeons to avian tuberculosis. Based on their clinical signs, 80 pigeons suspected with avian tuberculosis were subjected to the study. Out of the 51 identified isolates, 20 M. avium subsp. avium were subjected to the test. Drug susceptibly testing was performed according to the guidelines by Centers for Disease Control and Prevention and using proportional method. In the drug susceptibility testing, all isolates were resistant to streptomycin, kanamycin, ethionamide, and thiophene carboxylic acid hydrazide. Additionally, 3, 2, and 1 isolates were susceptible to isoniazid, rifampin, and ethambutol, respectively. To date, no study has documented the drug susceptibility testing of M. avium isolates from infected birds to avian tuberculosis. Pigeons are extensively kept in urban and rural areas for homing and racing

  15. Development of the "Three-step MACS": a novel strategy for isolating rare cell populations in the absence of known cell surface markers from complex animal tissue.

    PubMed

    Lee, Mathia Y; Lufkin, Thomas

    2012-07-01

    To circumvent the difficulty of isolating specific cell populations by MACS from dissociated complex animal tissue, when their proportions reached levels similar to that of the background, we developed the "Three-step MACS" strategy. Cells of interest are defined by their expression of a particular gene(s) of interest rather by than their natural cell surface markers or size. A two-component transgenic cell surface protein, for two sequential rounds of MACS, is expressed under the promoter control of the endogenous gene of interest by means of gene targeting and the generation of transgenic tissue. An initial step to remove dead cells is also used. Here, we describe proof-of-concept experiments, using the biotin acceptor peptide (BAP)-low-affinity nerve growth factor receptor as the two-component protein. The first component, the BAP, can be biotinylated in specific subsets of cells expressing a particular gene by expressing the biotinylating enzyme, hBirA = humanized BirA (hBirA), under the promoter control of another gene defining the specific subpopulation. We showed that a rare population of cells (1.1% of the 13.5 days postcoital mouse embryo) could be enriched to a sufficiently high purity (84.4%). From another sample with 0.1% of our cells of interest, we achieved a 40.3% pure sample. The low cost, speed, and technical ease of the Three-step MACS also make it scalable and hence, an ideal method for preparing sufficient quantities of biological samples for sensitive, high-throughput assays.

  16. The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter.

    PubMed

    Modali, Sita D; Zgurskaya, Helen I

    2011-08-01

    Escherichia coli MacAB-TolC is a tripartite macrolide efflux transporter driven by hydrolysis of ATP. In this complex, MacA is the periplasmic membrane fusion protein that stimulates the activity of MacB transporter and establishes the link with the outer membrane channel TolC. The molecular mechanism by which MacA stimulates MacB remains unknown. Here, we report that the periplasmic membrane proximal domain of MacA plays a critical role in functional MacA-MacB interactions and stimulation of MacB ATPase activity. Binding of MacA to MacB stabilizes the ATP-bound conformation of MacB, whereas interactions with both MacB and TolC affect the conformation of MacA. A single G353A substitution in the C-terminus of MacA inactivates MacAB-TolC function by changing the conformation of the membrane proximal domain of MacA and disrupting the proper assembly of the MacA-MacB complex. We propose that MacA acts in transport by promoting MacB transition into the closed ATP-bound conformation and in this respect, is similar to the periplasmic solute-binding proteins.

  17. Detection of Mycobacterium avium subspecies in the gut associated lymphoid tissue of slaughtered rabbits.

    PubMed

    Arrazuria, Rakel; Sevilla, Iker A; Molina, Elena; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A; Elguezabal, Natalia

    2015-06-11

    Rabbits are susceptible to infection by different species of the genus Mycobacterium. Particularly, development of specific lesions and isolation of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. paratuberculosis, both subspecies of the M. avium complex, has been reported in wildlife conditions. Although, rabbit meat production worldwide is 200 million tons per year, microbiological data on this source of meat is lacking and more specifically reports of mycobacterial presence in industrially reared rabbit for human consumption have not been published. To this end, we sought mycobacteria by microbiological and histopathological methods paying special attention to Mycobacterium avium subsp. paratuberculosis in rabbits from commercial rabbitries from the North East of Spain. M. avium subsp. paratuberculosis was not detected either by culture or PCR. However, Mycobacterium avium subsp. avium was detected in 15.15% (10/66) and Mycobacterium avium subsp. hominissuis was detected in 1.51% (1/66) of gut associated lymphoid tissue of sampled animals by PCR, whereas caecal contents were negative. 9% (6/66) of the animals presented gross lesions suggestive of lymphoid activation, 6% (4/66) presented granulomatous lesions and 3% (2/66) contained acid fast bacilli. Mycobacterial isolation from samples was not achieved, although colonies of Thermoactinomycetes sp. were identified by 16s rRNA sequencing in 6% (4/66) of sampled animals. Apparently healthy farmed rabbits that go to slaughter may carry M. avium subspecies in gut associated lymphoid tissue.

  18. Activation of macrophages and interference with CD4+ T-cell stimulation by Mycobacterium avium subspecies paratuberculosis and Mycobacterium avium subspecies avium

    PubMed Central

    Lage, Susanne Zur; Goethe, Ralph; Darji, Ayub; Valentin-Weigand, Peter; Weiss, Siegfried

    2003-01-01

    Mycobacterium avium subspecies paratuberculosis (M. ptb) and M. avium subspecies avium (M. avium) are closely related but exhibit significant differences in their interaction with the host immune system. The macrophage line, J774, was infected with M. ptb and M. avium and analysed for cytokine production and stimulatory capacity towards antigen-specific CD4+ T cells. Under all conditions J774 cells were activated to produce proinflammatory cytokines. No influence on the expression of major histocompatibility complex (MHC) class II, intracellular adhesion molecule-1 (ICAM-1), B7.1, B7.2 or CD40 was found. However, the antigen-specific stimulatory capacity of J774 cells for a CD4+ T-cell line was significantly inhibited after infection with M. ptb, but not with M. avium. When a T-cell hybridoma expressing a T-cell receptor identical to that of the T-cell line was used, this inhibition was not observed, suggesting that costimulation which is essential for the CD4+ T-cell line is influenced by the pathogenic bacterium M. ptb. PMID:12519304

  19. Trends in overall opportunistic illnesses, Pneumocystis carinii pneumonia, cerebral toxoplasmosis and Mycobacterium avium complex incidence rates over the 30 years of the HIV epidemic: a systematic review.

    PubMed

    Coelho, Lara; Veloso, Valdiléa Gonçalves; Grinsztejn, Beatriz; Luz, Paula Mendes

    2014-01-01

    The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle-income settings, with special attention given to studies from Brazil. We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included. Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle-income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle-income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses. Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle-income settings, multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  20. Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18

    PubMed Central

    Kim, S H; Cho, D; Kim, T S

    2001-01-01

    Interferon-gamma (IFN-γ) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-γ production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with κ leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-γ throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria. PMID:11260329

  1. The activity of grepafloxacin in two murine models of Mycobacterium avium infection.

    PubMed

    Cynamon, Michael H; Sklaney, Mary; Yeo, Anthony E T

    2004-06-01

    The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) were compared to clarithromycin (CLA; 100 mg/kg and 200 mg/kg), ethambutol (EMB; 100 mg/kg), and rifabutin (RBT; 10 mg/kg) using an intranasal (IN) infection model compared to an intravenous (IV) infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10(6) organisms and for the IV model about 10(7) organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks. At the initiation of therapy, an early control group was killed to determine the initial organism load. Three days following the completion of therapy, drug-treated groups of mice and the late control group were killed and the response to therapy measured. The most effective agents were CLA and RBT. GRE and EMB had modest activities in both the IN and the IV models. A matched comparison between IN and IV challenges for each of the agents used revealed greater suppression of MAC in the IN model compared to the IV model.

  2. Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T Cells.

    PubMed

    de Barros, Mariana; Perciano, Pedro Griffo; Dos Santos, Marcelo Henrique; De Oliveira, Leandro Licursi; Costa, Éderson D'Martin; Moreira, Maria Aparecida Scatamburlo

    2017-05-17

    Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis fruit, its complex with copper against Streptococcus spp. isolated from bovine mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC-T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with optical activity. Its vibrational spectrum in the infrared region showed absorption bands in the high-frequency region, as well as bands that can be attributed to the unconjugated and conjugated stretching of the free ligand. The complex was anhydrous. One of the tested bacterial strains was not sensitive to the compounds, while the other three had MIC values of 7.8 µg mL(-1) and minimum bactericidal concentration (MBC) values between 15.6 and 31.3 µg mL(-1). These two compounds are bacteriostatic, did not cause damage to the cell wall and, at sub-inhibitory concentrations, did not induce bacterial adhesion. The compounds were not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable antimicrobial properties and could potentially be used in bovine mastitis treatment.

  3. Inter- and Intra-subtype genotypic differences that differentiate Mycobacterium avium subspecies paratuberculosis strains

    PubMed Central

    2012-01-01

    Background Mycobacterium avium subspecies paratuberculosis (Map) is the aetiological agent of Johne’s disease or paratuberculosis and is included within the Mycobacterium avium complex (MAC). Map strains are of two major types often referred to as ‘Sheep’ or ‘S-type’ and ‘Cattle’ or ‘C-type’. With the advent of more discriminatory typing techniques it has been possible to further classify the S-type strains into two groups referred to as Type I and Type III. This study was undertaken to genotype a large panel of S-type small ruminant isolates from different hosts and geographical origins and to compare them with a large panel of well documented C-type isolates to assess the genetic diversity of these strain types. Methods used included Mycobacterial Interspersed Repetitive Units - Variable-Number Tandem Repeat analysis (MIRU-VNTR), analysis of Large Sequence Polymorphisms by PCR (LSP analysis), Single Nucleotide Polymorphism (SNP) analysis of gyr genes, Pulsed-Field Gel Electrophoresis (PFGE) and Restriction Fragment Length Polymorphism analysis coupled with hybridization to IS900 (IS900-RFLP) analysis. Results The presence of LSPA4 and absence of LSPA20 was confirmed in all 24 Map S-type strains analysed. SNPs within the gyr genes divided the S-type strains into types I and III. Twenty four PFGE multiplex profiles and eleven different IS900-RFLP profiles were identified among the S-type isolates, some of them not previously published. Both PFGE and IS900-RFLP segregated the S-type strains into types I and III and the results concurred with those of the gyr SNP analysis. Nine MIRU-VNTR genotypes were identified in these isolates. MIRU-VNTR analysis differentiated Map strains from other members of Mycobacterium avium Complex, and Map S-type from C-type but not type I from III. Pigmented Map isolates were found of type I or III. Conclusion This is the largest panel of S-type strains investigated to date. The S-type strains could be further divided

  4. Introduction to MAC CRM training

    NASA Technical Reports Server (NTRS)

    Brown, Donald D.

    1987-01-01

    The author introduces the Military Airlift Command (MAC) and its mission. A brief history of Cockpit Resource Management (CRM) as it relates to MAC is given. He also states why MAC is currently interested in CRM.

  5. Molecular typing and genetic characterization of Mycobacterium avium subsp. hominissuis isolates from humans and swine in Japan.

    PubMed

    Adachi, Takashi; Ichikawa, Kazuya; Inagaki, Takayuki; Moriyama, Makoto; Nakagawa, Taku; Ogawa, Kenji; Hasegawa, Yoshinori; Yagi, Tetsuya

    2016-11-01

    Mycobacterium avium subsp. hominissuis (MAH) causes disease in both humans and swine; however, the genetic variations in MAH isolates are unclear. The aim of this study was to elucidate the genetic variations in MAH isolates from humans and swine in Japan. We analysed the 16S-23S rDNA internal transcribed spacer (ITS) sequence and variable number of tandem repeats (VNTRs) using the Mycobacterium avium tandem repeat loci, prevalence of ISMav6 and clarithromycin resistance for MAH isolates from patients with pulmonary MAC (pMAC) disease (n=69), and HIV-seropositive and blood culture-positive (HIV-MAC) patients (n=28) and swine (n=23). In the minimum spanning tree based on VNTR analysis, swine MAC isolates belonged to a cluster distinguishable from that of human pMAC isolates. Isolates from HIV-MAC were scattered throughout both clusters. The three major distinct sequevars, Mav-A, Mav-B and Mav-F, were determined according to 16S-23S rDNA ITS sequence analysis in addition to three new sequevars, Mav-Q, Mav-R and Mav-S. Mav-A and Mav-F comprised the majority of human pMAC strains; in contrast, Mav-B predominated in swine isolates. Distribution of ITS sequevars in the minimum spanning tree based on VNTR analysis showed similar clusters of isolates from different origins, i.e. human pMAC, HIV-MAC and swine. These results, together with ISMav6 possession and clarithromycin resistance, revealed the genetic diversity of MAH strains recovered from humans and swine. Molecular epidemiology and genetic characterization in the present study showed the distinctive genetic evolutionary lineage of MAH strains isolated from human pMAC diseases and swine.

  6. Characterization of a Mycobacterium avium subsp. avium Operon Associated with Virulence and Drug Detoxification

    PubMed Central

    Viale, Mariana Noelia; Imperiale, Belén; Gioffre, Andrea Karina; Colombatti Olivieri, María Alejandra; Moyano, Roberto Damián; Morcillo, Nora; Santangelo, María de la Paz; Davis, William; Romano, María Isabel

    2014-01-01

    The lprG-p55 operon of Mycobacterium tuberculosis and Mycobacterium bovis is involved in the transport of toxic compounds. P55 is an efflux pump that provides resistance to several drugs, while LprG is a lipoprotein that modulates the host's immune response against mycobacteria. The knockout mutation of this operon severely reduces the replication of both mycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in the Mycobacterium avium complex, in this study, we assayed the effect of the deletion of lprG gene in the D4ER strain of Mycobacterium avium subsp. avium. The replacement of lprG gene with a hygromycin cassette caused a polar effect on the expression of p55. Also, a twofold decrease in ethidium bromide susceptibility was observed and the resistance to the antibiotics rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant strain. In addition, the mutation decreased the virulence of the bacteria in macrophages in vitro and in a mice model in vivo. These findings clearly indicate that functional LprG and P55 are necessary for the correct transport of toxic compounds and for the survival of MAA in vitro and in vivo. PMID:24967408

  7. Molecular analysis and MIRU-VNTR typing of Mycobacterium avium subsp. avium, 'hominissuis' and silvaticum strains of veterinary origin.

    PubMed

    Rónai, Zsuzsanna; Csivincsik, Ágnes; Dán, Ádám; Gyuranecz, Miklós

    2016-06-01

    Besides Mycobacterium avium subsp. paratuberculosis (MAP), M. avium subsp. avium (MAA), M. avium subsp. silvaticum (MAS), and 'M. avium subsp. hominissuis' (MAH) are equally important members of M. avium complex, with worldwide distribution and zoonotic potential. Genotypic discrimination is a prerequisite to epidemiological studies which can facilitate disease prevention through revealing infection sources and transmission routes. The primary aim of this study was to identify the genetic diversity within 135 MAA, 62 MAS, and 84 MAH strains isolated from wild and domestic mammals, reptiles and birds. Strains were tested for the presence of large sequence polymorphism LSP(A)17 and were submitted to Mycobacterial interspersed repetitive units-variable-number tandem repeat (MIRU-VNTR) analysis at 8 loci, including MIRU1, 2, 3, and 4, VNTR25, 32, and 259, and MATR9. In 12 strains hsp65 sequence code type was also determined. LSP(A)17 was present only in 19.9% of the strains. All LSP(A)17 positive strains belonged to subspecies MAH. The discriminatory power of the MIRU-VNTR loci set used reached 0.9228. Altogether 54 different genotypes were detected. Within MAH, MAA, and MAS strains 33, 16, and 5 different genotypes were observed. The described genotypes were not restricted to geographic regions or host species, but proved to be subspecies specific. Our knowledge about MAS is limited due to isolation and identification difficulties. This is the first study including a large number of MAS field strains. Our results demonstrate the high diversity of MAH and MAA strains and the relative uniformity of MAS strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter

    PubMed Central

    Lu, Shuo; Zgurskaya, Helen I.

    2012-01-01

    Summary MacB is a founding member of the Macrolide Exporter family of transporters belonging to the ATP-Binding Cassette superfamily. These proteins are broadly represented in genomes of both gram-positive and gram-negative bacteria and are implicated in virulence and protection against antibiotics and peptide toxins. MacB transporter functions together with MacA, a periplasmic membrane fusion protein, which stimulates MacB ATPase. In gram-negative bacteria, MacA is believed to couple ATP hydrolysis to transport of substrates across the outer membrane through a TolC-like channel. In this study, we report a real-time analysis of concurrent ATP hydrolysis and assembly of MacAB-TolC complex. MacB binds nucleotides with a low millimolar affinity and fast on- and off-rates. In contrast, MacA-MacB complex is formed with a nanomolar affinity, which further increases in the presence of ATP. Our results strongly suggest that association between MacA and MacB is stimulated by ATP binding to MacB but remains unchanged during ATP hydrolysis cycle. We also found that the large periplasmic loop of MacB plays the major role in coupling reactions separated in two different membranes. This loop is required for MacA-dependent stimulation of MacB ATPase and at the same time, contributes to recruitment of TolC into a trans-envelope complex. PMID:23057817

  9. Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter.

    PubMed

    Lu, Shuo; Zgurskaya, Helen I

    2012-12-01

    MacB is a founding member of the Macrolide Exporter family of transporters belonging to the ATP-Binding Cassette superfamily. These proteins are broadly represented in genomes of both Gram-positive and Gram-negative bacteria and are implicated in virulence and protection against antibiotics and peptide toxins. MacB transporter functions together with MacA, a periplasmic membrane fusion protein, which stimulates MacB ATPase. In Gram-negative bacteria, MacA is believed to couple ATP hydrolysis to transport of substrates across the outer membrane through a TolC-like channel. In this study, we report a real-time analysis of concurrent ATP hydrolysis and assembly of MacAB-TolC complex. MacB binds nucleotides with a low millimolar affinity and fast on- and off-rates. In contrast, MacA-MacB complex is formed with a nanomolar affinity, which further increases in the presence of ATP. Our results strongly suggest that association between MacA and MacB is stimulated by ATP binding to MacB but remains unchanged during ATP hydrolysis cycle. We also found that the large periplasmic loop of MacB plays the major role in coupling reactions separated in two different membranes. This loop is required for MacA-dependent stimulation of MacB ATPase and at the same time, contributes to recruitment of TolC into a trans-envelope complex. © 2012 Blackwell Publishing Ltd.

  10. Lymphadenitis in children is caused by Mycobacterium avium hominissuis and not related to ‘bird tuberculosis’

    PubMed Central

    de Haas, P. E. W.; Lindeboom, J. A.; Kuijper, E. J.; van Soolingen, D.

    2008-01-01

    Mycobacterium avium is the most commonly encountered mycobacterium species among non-Mycobacterium tuberculosis complex (nontuberculous mycobacteria) isolates worldwide and frequently causes lymphadenitis in children. During a multi-centre study in The Netherlands that was performed to determine the optimal treatment for mycobacterial lymphadenitis, concern was expressed in the media about the possible role of birds as sources of these M. avium infections, referred to as ‘bird tuberculosis.’ To examine the involvement of birds in mycobacterial lymphadenitis, 34 M. avium isolates from lymphadenitis cases were subjected to IS1245 restriction fragment length polymorphism (RFLP) typing. This genotyping method enables the distinction of the subspecies M. avium subsp. hominissuis and the ‘bird-type’ M. avium spp. avium. Highly variable RFLP patterns were found among the lymphadenitis M. avium isolates, and all belonged to the M. avium hominissuis subspecies. A relation to pet birds in the etiology of mycobacterial lymphadenitis could not be established, and the source of the infections may be environmental. PMID:18320245

  11. Mycobacterium avium in a shower linked to pulmonary disease.

    PubMed

    Falkinham, Joseph O; Iseman, Michael D; de Haas, Petra; van Soolingen, Dick

    2008-06-01

    Mycobacterium avium was isolated from hot and cold water samples and from sediment (biofilm) collected from the showerhead in the home of a woman with M. avium pulmonary disease lacking known M. avium risk factors. IS1245/IS1311 DNA fingerprinting demonstrated that M. avium isolates from the hot and cold water and showerhead sediment demonstrated a clonal relationship with the patient's M. avium isolate. The data provide evidence that showers may serve as sources of infection by waterborne M. avium.

  12. Genotyping of Mycobacterium avium subsp. avium isolates from naturally infected lofts of domestic pigeons in Ahvaz by IS901 RFLP

    PubMed Central

    Parvandar-Asadollahi, Kaveh; Mosavari, Nader; Mayahi, Mansoor

    2015-01-01

    Background and Objectives: Avian tuberculosis is one of the most important infections affecting most species of birds. Mycobacterium avium can not only infect all species of birds, but also infect some domesticated mammals. The most crucial aspect of control and eradication scheme is identification of infection sources and transmission routs. Molecular techniques such as restriction fragment length polymorphism and pulse field gel electrophoresis have been shown to be much more discriminatory and suitable for use in the epidemiological study. Materials and Methods: Eighty suspected pigeons to avian tuberculosis based on their clinical signs, were subjected to the study. Forty Mycobacterium avium subsp. avium isolates out of a total of 51 identified isolates were subjected to the test. Results: IS901-RFLP using Pvu II was successfully conducted and produced 7 patterns. The majority of isolates (60%) were RFLP type PI.1. This type was the most similar type to standard strain. However, all the patterns obtained in this study were different from the standard strain. Conclusion: The result of this study indicate that these isolates probably are limited to Khuzestan region. We recommend DNA fingerprinting differentiation of non tuberculous Mycobacteria particularly Mycobacterium avium complex isolated from infected birds and human to possibly find source of infections. PMID:26719782

  13. Genotyping of Mycobacterium avium subsp. avium isolates from naturally infected lofts of domestic pigeons in Ahvaz by IS901 RFLP.

    PubMed

    Parvandar-Asadollahi, Kaveh; Mosavari, Nader; Mayahi, Mansoor

    2015-10-01

    Avian tuberculosis is one of the most important infections affecting most species of birds. Mycobacterium avium can not only infect all species of birds, but also infect some domesticated mammals. The most crucial aspect of control and eradication scheme is identification of infection sources and transmission routs. Molecular techniques such as restriction fragment length polymorphism and pulse field gel electrophoresis have been shown to be much more discriminatory and suitable for use in the epidemiological study. Eighty suspected pigeons to avian tuberculosis based on their clinical signs, were subjected to the study. Forty Mycobacterium avium subsp. avium isolates out of a total of 51 identified isolates were subjected to the test. IS901-RFLP using Pvu II was successfully conducted and produced 7 patterns. The majority of isolates (60%) were RFLP type PI.1. This type was the most similar type to standard strain. However, all the patterns obtained in this study were different from the standard strain. The result of this study indicate that these isolates probably are limited to Khuzestan region. We recommend DNA fingerprinting differentiation of non tuberculous Mycobacteria particularly Mycobacterium avium complex isolated from infected birds and human to possibly find source of infections.

  14. Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

    PubMed Central

    Lee, Kang-In; Whang, Jake; Choi, Han-Gyu; Son, Yeo-Jin; Jeon, Haet Sal; Back, Yong Woo; Park, Hye-Soo; Paik, Seungwha; Park, Jeong-Kyu; Choi, Chul Hee; Kim, Hwa-Jung

    2016-01-01

    Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis. Enhanced reactive oxygen species production and JNK activation were essential for MAV2054-mediated apoptosis and MAV2054-induced interleukin-6, tumour necrosis factor, and monocyte chemoattractant protein-1 production. MAV2054 was targeted to the mitochondrial compartment of macrophages treated with MAV2054 and infected with M. avium. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in MAV2054-treated macrophages. Apoptotic response, reactive oxygen species production, and ΔΨm collapse were significantly increased in bone marrow-derived macrophages infected with Mycobacterium smegmatis expressing MAV2054, compared to that in M. smegmatis control. Furthermore, MAV2054 expression suppressed intracellular growth of M. smegmatis and increased the survival rate of M. smegmatis-infected mice. Thus, MAV2054 induces apoptosis via a mitochondrial pathway in macrophages, which may be an innate cellular response to limit intracellular M. avium multiplication. PMID:27901051

  15. MAC calorimeters and applications

    SciTech Connect

    MAC Collaboration

    1982-03-01

    The MAC detector at PEP features a large solid-angle electromagnetic/hadronic calorimeter system, augmented by magnetic charged-particle tracking, muon analysis and scintillator triggering. Its implementation in the context of electron-positron annihilation physics is described, with emphasis on the utilization of calorimetry.

  16. Recent results from MAC

    SciTech Connect

    MAC Collaboration

    1982-05-01

    Some preliminary results from the MAC detector at PEP are presented. These include measurements of the angular distribution of ..gamma gamma.., ..mu mu.. and tau tau final states, a determination of the tau lifetime, a measurement of R, and a presentation of the inclusive muon p/sub perpendicular/ distribution for hadronic events.

  17. Isolation of Mycobacterium avium from waterfowl with polycystic livers.

    USGS Publications Warehouse

    Roffe, Thomas J.

    1989-01-01

    An unusual gross appearance of avian tuberculosis, where fluid-filled thin-walled cysts are produced and grossly apparent in preference to granulomas, is presented. Histopathology confirmed the granulomatous nature of the lesions and the presence of intracellular acid-fast organisms. Mycobacterium avium complex was cultured from affected organs. The unusual gross presentation in these cases indicates the need to consider tuberculosis in the differential of cystic diseases of avian livers.

  18. HFGMC Enhancement of MAC/GMC

    NASA Technical Reports Server (NTRS)

    Arnold, Steven M.; Aboudi, Jacob; Pindera, Marek-Jerzy; Bednarcyk, Brett A.

    2006-01-01

    Additional information about a mathematical model denoted the high-fidelity generalized method of cells (HFGMC) and implementation of the HFGMC within version 4.0 of the MAC/GMC software has become available. MAC/GMC (Micromechanics Analysis Code With Generalized Method of Cells) was a topic of several prior NASA Tech Briefs articles, version 4.0 having been described in "Comprehensive Micromechanics-Analysis Code - Version 4.0" (LEW-17495-1), NASA Tech Briefs, Vol. 29, No. 9 (September 2005), page 54. MAC/GMC predicts elastic and inelastic thermomechanical responses of composite materials. MAC/GMC utilizes the generalized method of cells (GMC) - a model of micromechanics that predicts macroscopic responses of a composite material as functions of the properties, sizes, shapes, and responses of its constituents (e.g., matrix and fibers). The accuracy of the GMC is limited by neglect of coupling between normal and shear stresses. The HFGMC was developed by combining elements of the GMC and a related model, denoted the higher-order theory for functionally graded materials (HOTFGM), that can account for this coupling. Hence, the HFGMC enables simulation of stress and strain with greater accuracy. Some alterations of the MAC/GMC data structure were necessitated by the greater computational complexity of the HFGMC.

  19. Monolithic MACS micro resonators

    NASA Astrophysics Data System (ADS)

    Lehmann-Horn, J. A.; Jacquinot, J.-F.; Ginefri, J. C.; Bonhomme, C.; Sakellariou, D.

    2016-10-01

    Magic Angle Coil Spinning (MACS) aids improving the intrinsically low NMR sensitivity of heterogeneous microscopic samples. We report on the design and testing of a new type of monolithic 2D MACS resonators to overcome known limitations of conventional micro coils. The resonators' conductors were printed on dielectric substrate and tuned without utilizing lumped element capacitors. Self-resonance conditions have been computed by a hybrid FEM-MoM technique. Preliminary results reported here indicate robust mechanical stability, reduced eddy currents heating and negligible susceptibility effects. The gain in B1 /√{ P } is in agreement with the NMR sensitivity enhancement according to the principle of reciprocity. A sensitivity enhancement larger than 3 has been achieved in a monolithic micro resonator inside a standard 4 mm rotor at 500 MHz. These 2D resonators could offer higher performance micro-detection and ease of use of heterogeneous microscopic substances such as biomedical samples, microscopic specimens and thin film materials.

  20. Results from MAC

    SciTech Connect

    Chadwick, G.B.

    1983-05-01

    The MAC detector has been exposed at PEP to 40 pb/sup -1/ luminosity of e/sup +/e/sup -/ collisions. The detector is described and recent results of a continuing analysis of hadronic cross section, lepton pair charge asymmetry, Bhabha process, two photon final state and radiative ..mu.. pairs are given. New results on flavor tagging of hadronic events with an inclusive ..mu.., and some searches for new particles are presented.

  1. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    EPA Science Inventory

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  2. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    EPA Science Inventory

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  3. Mycobacterium avium ssp. paratuberculosis recombinant heat shock protein 70 interaction with different bovine antigen-presenting cells.

    PubMed

    Langelaar, M F M; Hope, J C; Rutten, V P M G; Noordhuizen, J P T M; van Eden, W; Koets, A P

    2005-03-01

    Abstract Heat shock proteins (Hsp) can deliver antigen into the major histocompatibility complex class I presentation pathway of antigen-presenting cells (APC), a process called cross priming, thus stimulating antigen-specific CD8+ T-cell reactions. Hsp were shown to elicit proinflammatory responses in APC. Both processes require interaction of Hsp with APC via specific receptors. This study describes the interaction of recombinant Hsp70 (rHsp70) of Mycobacterium avium subspecies paratuberculosis with bovine peripheral blood mononuclear cells that was restricted to CD14+ cells. Characterized monocyte-derived macrophages, monocyte-derived dendritic cells (DC) and BoMac, an immortalized bovine macrophage cell line, were used to investigate the interaction of rHsp70 with different bovine APC. Saturation of immature DC with high concentrations of rHsp70 is demonstrated, and it was found that interaction of rHsp70 with DC was related to the maturation stage of the DC. Involvement of CD91 as a cellular receptor for rHsp70 was demonstrated; however, competition studies with immature DC demonstrated that other receptors exist on bovine APC. These data suggest that rHsp70-based vaccines may be useful for the successful immunization of cattle.

  4. Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses.

    PubMed

    Okagawa, Tomohiro; Konnai, Satoru; Nishimori, Asami; Ikebuchi, Ryoyo; Mizorogi, Seiko; Nagata, Reiko; Kawaji, Satoko; Tanaka, Shogo; Kagawa, Yumiko; Murata, Shiro; Mori, Yasuyuki; Ohashi, Kazuhiko

    2015-10-19

    Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis. This infection is characterized by the functional exhaustion of T-cell responses to M. avium subsp. paratuberculosis antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in M. avium subsp. paratuberculosis-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the M. avium subsp. paratuberculosis antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of M. avium subsp. paratuberculosis infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced M. avium subsp. paratuberculosis-specific IFN-γ responses in blood from infected animals, and in vitro LAG-3 blockade enhanced IFN-γ production from M. avium subsp. paratuberculosis-specific CD4(+) and CD8(+) T cells. Taken together, the present data indicate that M. avium subsp. paratuberculosis-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of M. avium subsp. paratuberculosis-specific T-cell responses.

  5. Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses

    PubMed Central

    Okagawa, Tomohiro; Konnai, Satoru; Nishimori, Asami; Ikebuchi, Ryoyo; Mizorogi, Seiko; Nagata, Reiko; Kawaji, Satoko; Tanaka, Shogo; Kagawa, Yumiko; Murata, Shiro; Mori, Yasuyuki

    2015-01-01

    Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis. This infection is characterized by the functional exhaustion of T-cell responses to M. avium subsp. paratuberculosis antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in M. avium subsp. paratuberculosis-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the M. avium subsp. paratuberculosis antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of M. avium subsp. paratuberculosis infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced M. avium subsp. paratuberculosis-specific IFN-γ responses in blood from infected animals, and in vitro LAG-3 blockade enhanced IFN-γ production from M. avium subsp. paratuberculosis-specific CD4+ and CD8+ T cells. Taken together, the present data indicate that M. avium subsp. paratuberculosis-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of M. avium subsp. paratuberculosis-specific T-cell responses. PMID:26483406

  6. Divergent Immune Responses to Mycobacterium avium subsp. paratuberculosis Infection Correlate with Kinome Responses at the Site of Intestinal Infection

    PubMed Central

    Määttänen, Pekka; Trost, Brett; Scruten, Erin; Potter, Andrew; Kusalik, Anthony; Griebel, Philip

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle. M. avium subsp. paratuberculosis infects the gastrointestinal tract of calves, localizing and persisting primarily in the distal ileum. A high percentage of cattle exposed to M. avium subsp. paratuberculosis do not develop JD, but the mechanisms by which they resist infection are not understood. Here, we merge an established in vivo bovine intestinal segment model for M. avium subsp. paratuberculosis infection with bovine-specific peptide kinome arrays as a first step to understanding how infection influences host kinomic responses at the site of infection. Application of peptide arrays to in vivo tissue samples represents a critical and ambitious step in using this technology to understand host-pathogen interactions. Kinome analysis was performed on intestinal samples from 4 ileal segments subdivided into 10 separate compartments (6 M. avium subsp. paratuberculosis-infected compartments and 4 intra-animal controls) using bovine-specific peptide arrays. Kinome data sets clustered into two groups, suggesting unique binary responses to M. avium subsp. paratuberculosis. Similarly, two M. avium subsp. paratuberculosis-specific immune responses, characterized by different antibody, T cell proliferation, and gamma interferon (IFN-γ) responses, were also observed. Interestingly, the kinomic groupings segregated with the immune response groupings. Pathway and gene ontology analyses revealed that differences in innate immune and interleukin signaling and particular differences in the Wnt/β-catenin pathway distinguished the kinomic groupings. Collectively, kinome analysis of tissue samples offers insight into the complex cellular responses induced by M. avium subsp. paratuberculosis in the ileum and provides a novel method to understand mechanisms that alter the balance between cell-mediated and antibody responses to M. avium subsp. paratuberculosis infection. PMID

  7. Clarithromycin-ciprofloxacin-amikacin for therapy of Mycobacterium avium-Mycobacterium intracellulare bacteremia in patients with AIDS.

    PubMed Central

    de Lalla, F; Maserati, R; Scarpellini, P; Marone, P; Nicolin, R; Caccamo, F; Rigoli, R

    1992-01-01

    A combination of clarithromycin, ciprofloxacin, and amikacin for the treatment of Mycobacterium avium-Mycobacterium intracellulare bacteremia was evaluated in 12 AIDS patients. Mycobacteremia cleared in all patients by 2 to 8 weeks of treatment, and symptoms resolved. Four patients died; all had negative blood cultures until death, and disseminated M. avium-M. intracellulare complex infection was not considered the primary cause of death. PMID:1387303

  8. Splenic Involvement in Disseminated Mycobacterium avium-intracellulare Infection: Magnetic Resonance Imaging Findings.

    PubMed

    Clark, Haley; Khatri, Gaurav; Kapur, Payal; Pedrosa, Ivan

    2017-07-13

    We report the imaging findings of a patient with disseminated Mycobacterium avium-intracellulare complex presenting with multiple splenic lesions incompletely characterized on computed tomography in whom magnetic resonance imaging helped narrow the differential diagnosis. We discuss the magnetic resonance imaging findings suggesting the diagnosis, including the presence of focal susceptibility artifact within the lesions (ie, signal drop on T1 in-phase imaging), marked hypointensity on diffusion-weighted imaging, and faint progressive peripheral enhancement after contrast administration. We provide pathologic correlation to explain these imaging characteristics and a review of the literature of imaging characteristics in splenic involvement of M. avium-intracellulare complex infection.

  9. Iron Acquisition in Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Wang, Joyce; Moolji, Jalal; Dufort, Alex; Staffa, Alfredo; Domenech, Pilar; Reed, Michael B.

    2015-01-01

    ABSTRACT Mycobacterium avium subsp. paratuberculosis is a host-adapted pathogen that evolved from the environmental bacterium M. avium subsp. hominissuis through gene loss and gene acquisition. Growth of M. avium subsp. paratuberculosis in the laboratory is enhanced by supplementation of the media with the iron-binding siderophore mycobactin J. Here we examined the production of mycobactins by related organisms and searched for an alternative iron uptake system in M. avium subsp. paratuberculosis. Through thin-layer chromatography and radiolabeled iron-uptake studies, we showed that M. avium subsp. paratuberculosis is impaired for both mycobactin synthesis and iron acquisition. Consistent with these observations, we identified several mutations, including deletions, in M. avium subsp. paratuberculosis genes coding for mycobactin synthesis. Using a transposon-mediated mutagenesis screen conditional on growth without myobactin, we identified a potential mycobactin-independent iron uptake system on a M. avium subsp. paratuberculosis-specific genomic island, LSPP15. We obtained a transposon (Tn) mutant with a disruption in the LSPP15 gene MAP3776c for targeted study. The mutant manifests increased iron uptake as well as intracellular iron content, with genes downstream of the transposon insertion (MAP3775c to MAP3772c [MAP3775-2c]) upregulated as the result of a polar effect. As an independent confirmation, we observed the same iron uptake phenotypes by overexpressing MAP3775-2c in wild-type M. avium subsp. paratuberculosis. These data indicate that the horizontally acquired LSPP15 genes contribute to iron acquisition by M. avium subsp. paratuberculosis, potentially allowing the subsequent loss of siderophore production by this pathogen. IMPORTANCE Many microbes are able to scavenge iron from their surroundings by producing iron-chelating siderophores. One exception is Mycobacterium avium subsp. paratuberculosis, a fastidious, slow-growing animal pathogen whose growth

  10. Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

    PubMed Central

    Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

    2014-01-01

    Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

  11. Multichannel MAC Layer In Mobile Ad—Hoc Network

    NASA Astrophysics Data System (ADS)

    Logesh, K.; Rao, Samba Siva

    2010-11-01

    This paper we presented the design objectives and technical challenges in Multichannel MAC protocols in Mobile Ad-hoc Network. In IEEE 802.11 a/b/g standards allow use of multiple channels, only a single channel is popularly used, due to the lack of efficient protocols that enable use of Multiple Channels. Even though complex environments in ad hoc networks require a combined control of physical (PHY) and medium access control (MAC) layers resources in order to optimize performance. And also we discuss the characteristics of cross-layer frame and give a multichannel MAC approach.

  12. EISCAT observations during MAC/SINE and MAC/Epsilon

    NASA Technical Reports Server (NTRS)

    Roettger, J.; Hoppe, U.-P.; Hall, C.

    1989-01-01

    The EISCAT incoherent scatter radar facility in Tromsoe, Norway was operated during the MAC/SINE campaign for 78 hours in the period 10 June to 17 July 1987, and during the MAC/Epsilon campaign for 90 hours in the period 15 October to 5 November 1987. The VHF (224 MHz) radar operations during MAC/SINE yielded most interesting observations of strong coherent echoes from the mesopause region. Characteristic data of these polar mesospheric summer echoes are presented. The UHF (933 MHz) radar operations during MAC/Epsilon were done with 18 deg off zenith beam and allows the deduction of meridonal and horizontal wind components as well as radial velocity spectra in addition to the usual electron density profiles in the D and lower E regions. Some results from the VHF and UHF radars indicating the presence of gravity waves are examined.

  13. MYCOBACTERIUM AVIUM AND DRINKING WATER WHAT ARE THE CONNECTIONS?

    EPA Science Inventory

    Background: Human Mycobacterium avium infections are only known to be acquired from environmental sources such as water and soil. We compared M. avium isolates from clinical and drinking water sources using molecular tools. Methods: M. avium was isolated from water samples colle...

  14. MYCOBACTERIUM AVIUM AND DRINKING WATER WHAT ARE THE CONNECTIONS?

    EPA Science Inventory

    Background: Human Mycobacterium avium infections are only known to be acquired from environmental sources such as water and soil. We compared M. avium isolates from clinical and drinking water sources using molecular tools. Methods: M. avium was isolated from water samples colle...

  15. MAC layer security issues in wireless mesh networks

    NASA Astrophysics Data System (ADS)

    Reddy, K. Ganesh; Thilagam, P. Santhi

    2016-03-01

    Wireless Mesh Networks (WMNs) have emerged as a promising technology for a broad range of applications due to their self-organizing, self-configuring and self-healing capability, in addition to their low cost and easy maintenance. Securing WMNs is more challenging and complex issue due to their inherent characteristics such as shared wireless medium, multi-hop and inter-network communication, highly dynamic network topology and decentralized architecture. These vulnerable features expose the WMNs to several types of attacks in MAC layer. The existing MAC layer standards and implementations are inadequate to secure these features and fail to provide comprehensive security solutions to protect both backbone and client mesh. Hence, there is a need for developing efficient, scalable and integrated security solutions for WMNs. In this paper, we classify the MAC layer attacks and analyze the existing countermeasures. Based on attacks classification and countermeasures analysis, we derive the research directions to enhance the MAC layer security for WMNs.

  16. Fiverr MacGyver

    NASA Astrophysics Data System (ADS)

    Hut, Rolf; van de Giesen, Nick; Larson, Martha

    2014-05-01

    Crowdsourcing has become popular over the past years, also for scientific endeavors. There are many Citizen Science projects and crowdfunding platforms, such as Kickstarter, that are make helpful contributions to moving environmental science forward. An interesting underused source of useful crowd-derived contributions to research is the website Fiverr.com. On this platform, thousands of people, acting as small-scale freelance contractors, offer their skills in the form of services. The platform offers a chance for people to take a hobby, skill, or pastime and make it something more by reaching out to a wider audience and by receiving a payment in return for services. As is typical of other crowdsourcing platforms, the tasks are small and usually self contained. As the name Fiverr suggests, offers start at US5 to provide a particular service. Services offered range from graphic design, to messages sung or spoken with various styles or accents, to complete apps for Android or iPhone. Skill providers on the platform can accept a range of variation of definition in the tasks, some can be described in general terms, for others it is more appropriate to provide examples. Fiverr provides a central location for those offering skills and those needing services to find each other, it makes it possible to communicate and exchange files, to make payments, and it provides support for resolving disputes. In all cases, it is important to keep expectations aligned with the nature of the platform: quality can and will vary. Ultimately, the critical contribution of Fiverr is not to replace professional services or otherwise save money, but rather to provide access to a large group of people with specialized skills who are able to make a contribution on short notice. In the context of this session, it can be considered a pool of people with MacGyver skills lying in wait of a MacGyyer task to attack. There are many ways in which Fiverr tasks, which are called 'gigs', can be useful in

  17. MacB ABC transporter is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA.

    PubMed

    Lin, Hong Ting; Bavro, Vassiliy N; Barrera, Nelson P; Frankish, Helen M; Velamakanni, Saroj; van Veen, Hendrik W; Robinson, Carol V; Borges-Walmsley, M Inês; Walmsley, Adrian R

    2009-01-09

    Gram-negative bacteria utilize specialized machinery to translocate drugs and protein toxins across the inner and outer membranes, consisting of a tripartite complex composed of an inner membrane secondary or primary active transporter (IMP), a periplasmic membrane fusion protein, and an outer membrane channel. We have investigated the assembly and function of the MacAB/TolC system that confers resistance to macrolides in Escherichia coli. The membrane fusion protein MacA not only stabilizes the tripartite assembly by interacting with both the inner membrane protein MacB and the outer membrane protein TolC, but also has a role in regulating the function of MacB, apparently increasing its affinity for both erythromycin and ATP. Analysis of the kinetic behavior of ATP hydrolysis indicated that MacA promotes and stabilizes the ATP-binding form of the MacB transporter. For the first time, we have established unambiguously the dimeric nature of a noncanonic ABC transporter, MacB that has an N-terminal nucleotide binding domain, by means of nondissociating mass spectrometry, analytical ultracentrifugation, and atomic force microscopy. Structural studies of ABC transporters indicate that ATP is bound between a pair of nucleotide binding domains to stabilize a conformation in which the substrate-binding site is outward-facing. Consequently, our data suggest that in the presence of ATP the same conformation of MacB is promoted and stabilized by MacA. Thus, MacA would facilitate the delivery of drugs by MacB to TolC by enhancing the binding of drugs to it and inducing a conformation of MacB that is primed and competent for binding TolC. Our structural studies are an important first step in understanding how the tripartite complex is assembled.

  18. The thioamides methimazole and thiourea inhibit growth of M. avium Subspecies paratuberculosis in culture.

    PubMed

    Greenstein, Robert J; Su, Liya; Brown, Sheldon T

    2010-06-14

    Thyrotoxicosis is conceptualized as an "autoimmune" disease with no accepted infectious etiology. There are increasingly compelling data that another "autoimmune" affliction, Crohn disease, may be caused by Mycobacterium avium subspecies paratuberculosis (MAP). Like M. tb, MAP is systemic. We hypothesized that some cases of thyrotoxicosis may be initiated by a MAP infection. Because other thioamides treat tuberculosis, leprosy and M. avium complex, we hypothesized that a mode of action of some thioamide anti-thyrotoxicosis medications may include MAP growth inhibition. The effect of the thioamides, thiourea, methimazole and 6-propo-2-thiouracil (6-PTU) were studied in radiometric Bactec culture, on ten strains of three mycobacterial species (six of MAP, two of M. avium and two of M. tb. complex). Data are presented as "cumulative growth index," (cGI) or "percent decrease in cumulative GI" (%-DeltacGI). Methimazole was the most effective thioamide at inhibiting MAP growth. At 128microg/ml: MAP UCF-4; 65%-DeltacGI & MAP ATCC 19698; 90%-DeltacGI. Thiourea inhibited MAP "Ben" maximally; 70%-DeltacGI. Neither methimazole nor thiourea inhibited M. avium or M. tb. at the doses tested. 6-PTU has no inhibition on any strain studied, although a structurally analogous control, 5-PTU, was the most inhibitory thioamide tested. We show inhibition of MAP growth by the thioamides, thiourea and methimazole in culture. These data are compatible with the hypothesis that these thioamides may have anti-prokaryotic in addition to their well-established eukaryotic actions in thyrotoxic individuals.

  19. Keap1 regulates inflammatory signaling in Mycobacterium avium-infected human macrophages.

    PubMed

    Awuh, Jane Atesoh; Haug, Markus; Mildenberger, Jennifer; Marstad, Anne; Do, Chau Phuc Ngoc; Louet, Claire; Stenvik, Jørgen; Steigedal, Magnus; Damås, Jan Kristian; Halaas, Øyvind; Flo, Trude Helen

    2015-08-04

    Several mechanisms are involved in controlling intracellular survival of pathogenic mycobacteria in host macrophages, but how these mechanisms are regulated remains poorly understood. We report a role for Kelch-like ECH-associated protein 1 (Keap1), an oxidative stress sensor, in regulating inflammation induced by infection with Mycobacterium avium in human primary macrophages. By using confocal microscopy, we found that Keap1 associated with mycobacterial phagosomes in a time-dependent manner, whereas siRNA-mediated knockdown of Keap1 increased M. avium-induced expression of inflammatory cytokines and type I interferons (IFNs). We show evidence of a mechanism whereby Keap1, as part of an E3 ubiquitin ligase complex with Cul3 and Rbx1, facilitates ubiquitination and degradation of IκB kinase (IKK)-β thus terminating IKK activity. Keap1 knockdown led to increased nuclear translocation of transcription factors NF-κB, IFN regulatory factor (IRF) 1, and IRF5 driving the expression of inflammatory cytokines and IFN-β. Furthermore, knockdown of other members of the Cul3 ubiquitin ligase complex also led to increased cytokine expression, further implicating this ligase complex in the regulation of the IKK family. Finally, increased inflammatory responses in Keap1-silenced cells contributed to decreased intracellular growth of M. avium in primary human macrophages that was reconstituted with inhibitors of IKKβ or TANK-binding kinase 1 (TBK1). Taken together, we propose that Keap1 acts as a negative regulator for the control of inflammatory signaling in M. avium-infected human primary macrophages. Although this might be important to avoid sustained or overwhelming inflammation, our data suggest that a negative consequence could be facilitated growth of pathogens like M. avium inside macrophages.

  20. Molecular Epidemiology of Mycobacterium avium subsp. paratuberculosis Isolates Recovered from Wild Animal Species

    PubMed Central

    Motiwala, Alifiya S.; Amonsin, Alongkorn; Strother, Megan; Manning, Elizabeth J. B.; Kapur, Vivek; Sreevatsan, Srinand

    2004-01-01

    Mycobacterial isolates were obtained by radiometric culture from 33 different species of captive or free-ranging animals (n = 106) and environmental sources (n = 3) from six geographic zones within the United States. The identities of all 109 isolates were confirmed by using mycobactin J dependence and characterization of five well-defined molecular markers, including two integration loci of IS900 (loci L1 and L9), one Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis)-specific sequence (locus 251), and one M. avium subsp. avium-specific marker (IS1245), as well as hsp65 and IS1311 restriction endonuclease analyses. Seventy-six acid-fast isolates were identified as M. paratuberculosis, 15 were identified as belonging to the M. avium-M. intracellulare complex (but not M. paratuberculosis), and the remaining 18 were identified as mycobacteria outside the M. avium-M. intracellulare complex. Fingerprinting by multiplex PCR for IS900 integration loci clustered 67 of the 76 M. paratuberculosis strains into a single clade (designated clade A18) and had a Simpson's diversity index (D) of 0.53. In contrast, sequence-based characterization of a recently identified M. paratuberculosis short sequence repeat (SSR) region enabled the differentiation of the M. paratuberculosis isolates in clade A18 into seven distinct alleles (D = 0.75). The analysis revealed eight subtypes among the 33 species of animals, suggesting the interspecies transmission of specific strains. Taken together, the results of our analyses demonstrate that SSR analysis enables the genetic characterization of M. paratuberculosis isolates from different host species and provide evidence for the host specificity of some M. paratuberculosis strains as well as sharing of strains between wild and domesticated animal species. PMID:15071028

  1. Trypanosoma avium of raptors (Falconiformes): phylogeny and identification of vectors.

    PubMed

    Votýpka, J; Oborník, M; Volf, P; Svobodová, M; Lukes, J

    2002-09-01

    Avian trypanosomes are widespread parasites of birds, the transmission of which remains mostly unclear, with various blood-sucking insects mentioned as possible vectors. A search for vectors of trypanosomes of sparrowhawk (Accipiter nisus), buzzard (Buteo buteo), lesser-spotted eagle (Aquila pomarina) and kestrel (Falco tinnunculus) was performed in Czech and Slovak Republics. Black flies (Eusimulium spp.), hippoboscid flies (Ornithomyia avicularia), mosquitoes (Culex pipiens pipiens) and biting midges (Culicoides spp.), trapped while attempting to feed on raptor nestlings, were found to contain trypanosomatids in their intestine. Trypanosomes from the raptors and blood-sucking insects were isolated, and their 18S rRNA sequences were used for species identification and for the inference of intra- and interspecific relationships. Together with the trypanosome isolated from a black fly, the bird trypanosomes formed a well-supported Trypanosoma avium clade. The isolates derived from hippoboscid flies and mosquitoes are most likely also avian trypanosomes infecting birds other than the studied raptors. Analysis of the kinetoplast, that has features characteristic for the avian trypanosomes (minicircle size; dimensions of the kinetoplast disc), provided further evidence for the identification of vectors. It is suggested that all trypanosomes isolated from raptors included in this study belong to the T. avium complex and are transmitted by the ornithophilic simuliids such as Eusimulium securiforme.

  2. Functional implications of an intermeshing cogwheel-like interaction between TolC and MacA in the action of macrolide-specific efflux pump MacAB-TolC.

    PubMed

    Xu, Yongbin; Song, Saemee; Moeller, Arne; Kim, Nahee; Piao, Shunfu; Sim, Se-Hoon; Kang, Mooseok; Yu, Wookyung; Cho, Hyun-Soo; Chang, Iksoo; Lee, Kangseok; Ha, Nam-Chul

    2011-04-15

    Macrolide-specific efflux pump MacAB-TolC has been identified in diverse gram-negative bacteria including Escherichia coli. The inner membrane transporter MacB requires the outer membrane factor TolC and the periplasmic adaptor protein MacA to form a functional tripartite complex. In this study, we used a chimeric protein containing the tip region of the TolC α-barrel to investigate the role of the TolC α-barrel tip region with regard to its interaction with MacA. The chimeric protein formed a stable complex with MacA, and the complex formation was abolished by substitution at the functionally essential residues located at the MacA α-helical tip region. Electron microscopic study delineated that this complex was made by tip-to-tip interaction between the tip regions of the α-barrels of TolC and MacA, which correlated well with the TolC and MacA complex calculated by molecular dynamics. Taken together, our results demonstrate that the MacA hexamer interacts with TolC in a tip-to-tip manner, and implies the manner by which MacA induces opening of the TolC channel.

  3. Disparate host immunity to Mycobacterium avium subsp. paratuberculosis antigens in calves inoculated with M. avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii and M. bovis

    USDA-ARS?s Scientific Manuscript database

    Cross-reactivity of mycobacterial antigens in immune-based diagnostic assays has been a major concern and criticism of current tests for the detection of paratuberculosis. In the present study, host immune responses to antigen preparations of Mycobacterium avium subsp. paratuberculosis (MAP), consis...

  4. Disseminated Mycobacterium avium infection in a cat

    PubMed Central

    Barry, Maureen; Taylor, Judith; Woods, Paul

    2002-01-01

    A domestic shorthair cat was presented for lethargy and ataxia. Clinical findings included an abdominal mass, lumbosacral pain, ataxia. Aspirates from the liver and lymph nodes revealed intracellular, negative-staining rods. Treatment for presumptive mycobacterium infection was unsuccessful and the cat was euthanized. Disseminated Mycobacterium avium was confirmed on culture. PMID:12001504

  5. Iron-chelating compound from Mycobacterium avium.

    PubMed Central

    McCullough, W G; Merkal, R S

    1976-01-01

    A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine. PMID:185194

  6. Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections

    PubMed Central

    Khare, Sangeeta; Drake, Kenneth L.; Lawhon, Sara D.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris. A.; Adams, Leslie Garry

    2016-01-01

    It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer’s patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

  7. Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections.

    PubMed

    Khare, Sangeeta; Drake, Kenneth L; Lawhon, Sara D; Nunes, Jairo E S; Figueiredo, Josely F; Rossetti, Carlos A; Gull, Tamara; Everts, Robin E; Lewin, Harris A; Adams, Leslie Garry

    It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer's patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

  8. Refurbishing MacIntyre's Account of Practice

    ERIC Educational Resources Information Center

    Hager, Paul

    2011-01-01

    According to Alasdair MacIntyre's influential account of practices, "teaching itself is not a practice, but a set of skills and habits put to the service of a variety of practices" (MacIntyre and Dunne, 2002, p. 5). Various philosophers of education have responded to and critiqued MacIntyre's position, most notably in a Special Issue of the…

  9. The many faces of Mac-1 in autoimmune disease.

    PubMed

    Rosetti, Florencia; Mayadas, Tanya N

    2016-01-01

    Mac-1 (CD11b/CD18) is a β2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcγR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Mycobacterium avium infection in mice is associated with time-related expression of Th1 and Th2 CD4+ T-lymphocyte response.

    PubMed Central

    Azouaou, N; Petrofsky, M; Young, L S; Bermudez, L E

    1997-01-01

    Disseminated infection caused by organisms of Mycobacterium avium complex is common in acquired immune deficiency syndrome (AIDS) patients. M. avium is an intracellular bacterium that multiplies within macrophages. We examined the effect of M. avium infection on the T-helper cell response in C57/BL/6 black mice. At weekly intervals, CD4+ T-cells were isolated from spleens and lines were created. T-cell lines were exposed to sonicated M. avium in the presence of feeder cells and macrophages and the supernatant were collected to measure the concentrations of interferon-gamma (IFN-gamma and interleukin-10 (IL-10). Production of IFN-gamma in CD4+ T-cells obtained from uninfected mice did not vary significantly during the 5 weeks. Levels of IFN-gamma produced by T-cell lines of infected mice were similar to the control mice during the first 2 weeks but significantly reduced (approximately 30 ng/ml) thereafter. In contrast, production of IL-10 by T-cell lines of infected mice was in a range of 190 to 342 pg/ml in weeks 1, 2 and 3, but increased to an average of 1300 pg/ml at weeks 4 and 5. Pre-immunized mice, when infected with M. avium strain 101, showed a different profile of T-cell cytokines, with high IFN-gamma and low IL-10 production. Proteins purified from a number of disease-associated (D-A) and non-D-A strains of M. avium were tested for the ability to induce IL-10. 65,000 MW and 60,000 MW proteins of M. avium induced significantly more IL-10 than 45,000 MW, 33,000 MW and 27,000 MW proteins. These results showed that M. avium predominantly stimulates either Th1 or Th2 T-helper cells according to the phase of the infection. PMID:9301531

  11. Immunization with a DNA Vaccine Cocktail Induces a Th1 Response and Protects Mice Against Mycobacterium avium subsp. paratuberculosis Challenge

    USDA-ARS?s Scientific Manuscript database

    Several novel antigens of Mycobacterium avium subsp. paratuberculosis have been studied as vaccine components and their immunogenicity has been evaluated. Previously, we reported that 85 antigen complex (85A, 85B, and 85C), superoxide dismutase (SOD), and 35kDa protein could induce significant lymph...

  12. Mycobacterium avium subsp. avium found in raptors exposed to infected domestic fowl.

    PubMed

    Kriz, Petr; Kaevska, Marija; Bartejsova, Iva; Pavlik, Ivo

    2013-09-01

    We report a case of a falcon breeding facility, where raptors (both diurnal and nocturnal) were raised in contact with domestic fowl (Gallus gallus f. domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental samples from 20 raptors and four common ravens (Corvus corax) were collected. Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the flock of domestic fowl and one of the infected raptors had the same origin (zoological collection), they might have had a common source of colonization/infection. However, the detection of M. a. avium in feces of three other raptors may point at transmission of the agent between the birds in the facility. Contact of raptors with domestic fowl infected by M. a. avium may pose a risk for transmission of the infection for them; however, raptors from the falcon breeding facility seemed to be relatively resistant to the infection.

  13. Experimental inoculation of BFDV-positive budgerigars (Melopsittacus undulatus) with two Mycobacterium avium subsp. avium isolates.

    PubMed

    Ledwoń, Aleksandra; Sapierzyński, Rafał; Augustynowicz-Kopeć, Ewa; Szeleszczuk, Piotr; Kozak, Marcin

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group.

  14. Experimental Inoculation of BFDV-Positive Budgerigars (Melopsittacus undulatus) with Two Mycobacterium avium subsp. avium Isolates

    PubMed Central

    Sapierzyński, Rafał; Szeleszczuk, Piotr

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group. PMID:24738057

  15. Prediction of Quinolone Activity against Mycobacterium avium by Molecular Topology and Virtual Computational Screening

    PubMed Central

    Gozalbes, Rafael; Brun-Pascaud, Monique; García-Domenech, Ramon; Gálvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

    2000-01-01

    We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti-M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (r2 = 0.88; r2cv [cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the M. avium- M. intracellulare complex, with MICs of 0.2, 0.4, and 0.9 μg/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity. PMID:10991858

  16. Mac OS X for Astronomy

    NASA Astrophysics Data System (ADS)

    Pierfederici, F.; Pirzkal, N.; Hook, R. N.

    Mac OS X is the new Unix based version of the Macintosh operating system. It combines a high performance DisplayPDF user interface with a standard BSD UNIX subsystem and provides users with simultaneous access to a broad range of applications which were not previously available on a single system such as Microsoft Office and Adobe Photoshop, as well as legacy X11-based scientific tools and packages like IRAF, SuperMongo, MIDAS, etc. The combination of a modern GUI layered on top of a familiar UNIX environment paves the way for new, more flexible and powerful astronomical tools to be developed while assuring compatibility with already existing, older programs. In this paper, we outline the strengths of the Mac OS X platform in a scientific environment, astronomy in particular, and point to the numerous astronomical software packages available for this platform; most notably the Scisoft collection which we have compiled.

  17. Multifunction automated crawling system (MACS)

    NASA Astrophysics Data System (ADS)

    Bar-Cohen, Yoseph; Backes, Paul G.; Joffe, Benjamin

    1996-11-01

    Nondestructive evaluation instruments and sensors are becoming smaller with enhanced computer controlled capability and increasingly use commercially available hardware and software. Further, robotic instruments are being developed to serve as mobility platforms allowing automation of the inspection process. This combination of miniaturized sensing and robotics technology enables hybrid miniature technology solutions for identified aircraft inspection needs. Integration of inspection and robotics technologies is benefited by the use of a standard computing platform. JPL investigated the application of telerobotic technology to inspection of aircraft structures using capabilities that were developed for use in space exploration. A miniature crawler that can travel on the surface of aircraft using suction cups for adherence was developed and is called multifunction automated crawling systems (MACS). MACS is an operational tool that can perform rapid large area inspection of aircraft, which has a relatively large platform to carry miniature inspection instruments payload. The capability of MACS and the trend towards autonomous inspection crawlers will be reviewed and discussed in this paper.

  18. Loci of Mycobacterium avium ser2 gene cluster and their functions.

    PubMed Central

    Mills, J A; McNeil, M R; Belisle, J T; Jacobs, W R; Brennan, P J

    1994-01-01

    The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit. PMID:8050992

  19. Genetic IS901 RFLP diversity among Mycobacterium avium subsp. avium isolates from four pheasant flocks.

    PubMed

    Moravkova, Monika; Lamka, Jiri; Slany, Michal; Pavlik, Ivo

    2013-01-01

    IS901 RFLP analysis of 36 Mycobacterium avium subsp. avium (MAA) isolates from 15 pheasants (Phasianus colchicus) and two goshawks (Accipiter gentilis) from four pheasant farms was performed. Using this method, six different IS901 RFLP types (E, F, G, M, Q, and V) were identified. The distribution of IS901 RFLP profiles was tightly linked to individual flocks. Matching IS901 RFLP profiles observed in the present study indicate MAA transmission between pheasants and goshawks in the same locality. In two flocks, different pheasants within a flock as well as in various organs of five individual pheasants were found to have two distinct IS901 RFLP profiles.

  20. Mycobacterium avium subspecies impair dendritic cell maturation.

    PubMed

    Basler, Tina; Brumshagen, Christina; Beineke, Andreas; Goethe, Ralph; Bäumer, Wolfgang

    2013-10-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, a chronic, granulomatous enteritis of ruminants. Dendritic cells (DC) of the gut are ideally placed to combat invading mycobacteria; however, little is known about their interaction with MAP. Here, we investigated the interaction of MAP and the closely related M. avium ssp. avium (MAA) with murine DC and the effect of infected macrophages on DC maturation. The infection of DC with MAP or MAA induced DC maturation, which differed to that of LPS as maturation was accompanied by higher production of IL-10 and lower production of IL-12. Treatment of maturing DC with supernatants from mycobacteria-infected macrophages resulted in impaired DC maturation, leading to a semi-mature, tolerogenic DC phenotype expressing low levels of MHCII, CD86 and TNF-α after LPS stimulation. Though the cells were not completely differentiated they responded with an increased IL-10 and a decreased IL-12 production. Using recombinant cytokines we provide evidence that the semi-mature DC phenotype results from a combination of secreted cytokines and released antigenic mycobacterial components of the infected macrophage. Our results indicate that MAP and MAA are able to subvert DC function directly by infecting and indirectly via the milieu created by infected macrophages.

  1. Identification of Mycobacterium avium subsp. hominissuis Isolated From Drinking Water

    EPA Science Inventory

    Mycobacterium avium (MA) is divided into four subspecies based primarily on host-range and consists of MA subsp. avium (birds), MA subsp. silvaticum (wood pigeons), MA subsp. paratuberculosis (broad, poorly-defined host range), and the recently described MA subsp. hominissuis (hu...

  2. Identification of Mycobacterium avium subsp. hominissuis Isolated From Drinking Water

    EPA Science Inventory

    Mycobacterium avium (MA) is divided into four subspecies based primarily on host-range and consists of MA subsp. avium (birds), MA subsp. silvaticum (wood pigeons), MA subsp. paratuberculosis (broad, poorly-defined host range), and the recently described MA subsp. hominissuis (hu...

  3. Bacteriocin from Honeybee Beebread Enterococcus avium, Active against Listeria monocytogenes

    PubMed Central

    Audisio, M. Carina; Terzolo, Horacio R.; Apella, María C.

    2005-01-01

    Enterococcus avium isolated from Apis mellifera beebread produces a thermoresistant bacteriocin with a strain-dependent inhibitory effect on Listeria and without effect on gram-negative bacteria. The bacteriocin appeared to be a polypeptide of about 6 kDa. Genetic analyses revealed no extrachromosomal material in E. avium. PMID:15933045

  4. Formulation of indomethacin emulsion using biopolymer of Prunus avium.

    PubMed

    Verma, Shivangi; Dabral, Prashant; Rana, Vinod; Upadhaya, Kumud; Bhardwaj

    2012-03-01

    The aim of the investigation was to formulate Indomethacin Emulsion using Bio-polymer as Emulsifier. Different batches of emulsions were prepared by varying concentration of biopolymer prunus avium. Based evaluation of the prepared polymers, a conclusion can be drawn that in the Prunus avium bio-material can serve as a promising film forming agent for formulating various drug.

  5. Assessment of yeast Saccharomyces cerevisiae component binding to Mycobacterium avium subspecies paratuberculosis using bovine epithelial cells.

    PubMed

    Li, Ziwei; You, Qiumei; Ossa, Faisury; Mead, Philip; Quinton, Margaret; Karrow, Niel A

    2016-03-01

    Since yeast Saccharomyces cerevisiae and its components are being used for the prevention and treatment of enteric diseases in different species, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium spp. paratuberculosis (MAP). This study aimed to identify potential yeast derivatives that may be used to help prevent MAP infection. The adherence of mCherry-labeled MAP to bovine mammary epithelial cell line (MAC-T cells) and bovine primary epithelial cells (BECs) co-cultured with yeast cell wall components (CWCs) from four different yeast strains (A, B, C and D) and two forms of dead yeast from strain A was investigated. The CWCs from all four yeast strains and the other two forms of dead yeast from strain A reduced MAP adhesion to MAC-T cells and BECs in a concentration-dependent manner after 6-h of exposure, with the dead yeast having the greatest effect. The following in vitro binding studies suggest that dead yeast and its' CWCs may be useful for reducing risk of MAP infection.

  6. The Thioamides Methimazole and Thiourea Inhibit Growth of M. avium Subspecies paratuberculosis in Culture

    PubMed Central

    Greenstein, Robert J.; Su, Liya; Brown, Sheldon T.

    2010-01-01

    Background Thyrotoxicosis is conceptualized as an “autoimmune” disease with no accepted infectious etiology. There are increasingly compelling data that another “autoimmune” affliction, Crohn disease, may be caused by Mycobacterium avium subspecies paratuberculosis (MAP). Like M. tb, MAP is systemic. We hypothesized that some cases of thyrotoxicosis may be initiated by a MAP infection. Because other thioamides treat tuberculosis, leprosy and M. avium complex, we hypothesized that a mode of action of some thioamide anti-thyrotoxicosis medications may include MAP growth inhibition. Methods The effect of the thioamides, thiourea, methimazole and 6-propo-2-thiouracil (6-PTU) were studied in radiometric Bactec® culture, on ten strains of three mycobacterial species (six of MAP, two of M. avium and two of M. tb. complex). Data are presented as “cumulative growth index,” (cGI) or “percent decrease in cumulative GI” (%-ΔcGI). Principal Findings Methimazole was the most effective thioamide at inhibiting MAP growth. At 128µg/ml: MAP UCF-4; 65%-ΔcGI & MAP ATCC 19698; 90%-ΔcGI. Thiourea inhibited MAP “Ben” maximally; 70%-ΔcGI. Neither methimazole nor thiourea inhibited M. avium or M. tb. at the doses tested. 6-PTU has no inhibition on any strain studied, although a structurally analogous control, 5-PTU, was the most inhibitory thioamide tested. Significance We show inhibition of MAP growth by the thioamides, thiourea and methimazole in culture. These data are compatible with the hypothesis that these thioamides may have anti-prokaryotic in addition to their well-established eukaryotic actions in thyrotoxic individuals. PMID:20559419

  7. Comparative analysis of the genomes of clinical isolates of Mycobacterium avium subsp. hominissuis regarding virulence-related genes.

    PubMed

    Jeffrey, Brendan; Rose, Sasha J; Gilbert, Kerrigan; Lewis, Matthew; Bermudez, Luiz E

    2017-07-01

    Mycobacterium avium subsp. hominissuis is a member of the M. avium complex, a heterogeneous group of bacteria that cause lung infection in immunocompetent patients or disseminated infection in patients with immunosuppression. The bacteria belonging to this complex have variable virulence, depending on the strain considered, and therefore a representative of the most common clinical phenotype was analysed. The genomic sequences of four M. avium subsp. hominissuis isolates obtained from clinical specimens were completed. Mav101, Mav100 and MavA5 were isolated from the blood of patients with AIDS. MavA5 was disseminated from the lung, while Mav3388 was isolated from the lungs of a patient with chronic lung disease. The sequences were annotated using the published Mav104 genome as a blueprint. Functional and virulence analyses of the sequences were carried out. Mice studies comparing the virulence of the strains were performed. Findings showed that while Mav101 was very similar to Mav104, there were numerous differences between Mav104 and the remaining strains at nucleotide and predicted protein levels. The presence of genes associated with biofilm formation and several known virulence-related genes were sometimes differentially present among the isolates, suggesting overlapping functions by different genetic determinants. The sequences provided important information about M. avium heterogenicity and evolution as a pathogen. The limitation is the lack of understanding on possible overlapping functions of genes/proteins.

  8. Avian mycobacteriosis caused by Mycobacterium avium subspecies avium in four ornamental birds and in vitro drug sensitivity testing of isolates.

    PubMed

    Stepień-Pyśniak, Dagmara; Puk, Krzysztof; Guz, Leszek; Wawrzyniak, Agata; Marek, Agnieszka; Kosikowska, Urszula

    2016-01-01

    Avian tuberculosis, one of the most important diseases affecting various species of birds, is most often caused by Mycobacterium (M.) avium. This report describes cases of M. avium subsp. avium (MAA) infection in a white-crested Holland dwarf rooster, a male and a female golden pheasant and a male peacock. We also investigated the prevalence of mycobacteria in 60 other birds and 40 alpacas. Tissue samples of necropsied birds were cultured for mycobacteria. From non-necropsied 60 other birds and alpacas only faecal samples were collected. Clinical signs in the affected white-crested Holland cock included gradual loss of body weight and hoarse attempts at crowing during its last 3 weeks, with a dramatic loss of body condition and depression over the final week. Only slight weakening was observed in the peacock just before its death, and the golden pheasants died suddenly. Diagnosis was confirmed by microbiological, molecular and pathological results. Mycobacterium avium subsp. avium strains were isolated from the internal organs of the affected birds. Only one faecal sample from 60 other birds was culture- and PCR-positive for M. avium subsp. avium, while another one was only PCR-positive for M. chelonae. We did not isolate any Mycobacterium spp. from faecal samples of alpacas and all of them were PCR-negative. All 18 isolated M. avium strains were resistant to rifampicin, isoniazid, ethambutol, ethionamide, capreomycin and ofloxacin, and susceptible to cycloserine and streptomycin.

  9. Apa antigen of Mycobacterium avium subsp. paratuberculosis as a target for species-specific immunodetection of the bacteria in infected tissues of cattle with paratuberculosis.

    PubMed

    Souza, Giliane S; Rodrigues, Ana Bárbara F; Gioffré, Andrea; Romano, Maria I; Carvalho, Eulógio C Q; Ventura, Thatiana L B; Lasunskaia, Elena B

    2011-09-15

    Comparative genomics of Mycobacterium spp. have revealed conservative genes and respective proteins differently expressed in mycobacteria that could be used as targets for the species-specific immunodiagnostics. The alanine and proline-rich antigen Apa is a mycobacterial protein that present significant variability in primary sequence length and composition between members of M. avium and M. tuberculosis complexes. In this study, the recombinant Apa protein encoded by the MAP1569/ModD gene of M. avium subsp. paratuberculosis (Map) was used to generate a panel of monoclonal antibodies which were shown to recognize the most important veterinary pathogens of the M. avium complex, specifically Map and M. avium subsp. hominissuis, and which did not cross-react with M. bovis or M. tuberculosis. The produced antibodies were demonstrated to be a useful tool for the species-specific immunofluorescence or immunohistochemical detection of Map in experimentally infected cell cultures or intestinal tissues from cattle with bovine paratuberculosis and, additionally, they may be employed for the discrimination of pathogenic M. avium subspecies via Western blotting. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Identification of a copper-induced intramolecular interaction in the transcription factor Mac1 from Saccharomyces cerevisiae.

    PubMed Central

    Jensen, L T; Winge, D R

    1998-01-01

    Mac1 mediates copper (Cu)-dependent expression of genes involved in high-affinity uptake of copper ions in Saccharomyces cerevisiae. Mac1 is a transcriptional activator in Cu-deficient cells, but is inhibited in Cu-replete cells. Mac1 resides within the nucleus in both Cu-deficient and Cu-loaded cells. Cu inhibition of Mac1 appears to result from binding of eight copper ions within a C-terminal segment consisting of two Cys-rich motifs. In addition, two zinc ions are bound within the N-terminal DNA-binding domain. Only 4-5 mol. eq. Cu are bound to a mutant Mac1 (His279Gln substitution) that is impervious to Cu inhibition. The CuMac1 complex is luminescent, indicative of copper bound in the Cu(I) state. Cu binding induces a molecular switch resulting in an intramolecular interaction in Mac1 between the N-terminal DNA-binding domain and the C-terminal activation domain. This allosteric interaction is Cu dependent and is not observed when Mac1 contained the mutant His279Gln substitution. Fusion of the minimal DNA-binding domain of Mac1 (residues 1-159) to the minimal Cu-binding activation domain (residues 252-341) yields a functional Cu-regulated transcriptional activator. These results suggest that Cu repression of Mac1 arises from a Cu-induced intramolecular interaction that inhibits both DNA binding and transactivation activities. PMID:9736617

  11. Wound healing in Mac-1 deficient mice.

    PubMed

    Chen, Lin; Nagaraja, Sridevi; Zhou, Jian; Zhao, Yan; Fine, David; Mitrophanov, Alexander Y; Reifman, Jaques; DiPietro, Luisa A

    2017-05-01

    Mac-1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac-1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac-1(-/-) mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. This study examined whether Mac-1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac-1 deficient (Mac-1(-/-) ) and wild type (WT) mice, and wound healing outcomes were examined. Mac-1 deficient mice exhibited a normal rate of wound closure, generally normal levels of total collagen, and nearly normal synthesis and distribution of collagens I and III. In incisional wounds, wound breaking strength was similar for Mac-1(-/-) and WT mice. Wounds of Mac-1 deficient mice displayed normal total macrophage content, although macrophage phenotype markers were skewed as compared to WT. Interestingly, amounts of TGF-β1 and its downstream signaling molecules, SMAD2 and SMAD3, were significantly decreased in the wounds of Mac-1 deficient mice compared to WT. The results suggest that Mac-1 deficiency has little impact on the healing of small excisional and incisional wounds. Moreover, the findings demonstrate that the effect of single genetic deficiencies on wound healing may markedly differ among wound models. These conclusions have implications for the interpretation of the many prior studies that utilize a single model system to examine wound healing outcomes in genetically deficient mice. © 2017 by the Wound Healing Society.

  12. Inactivation of Mycobacterium avium with monochloramine.

    PubMed

    Luh, Jeanne; Tong, Ning; Raskin, Lutgarde; Mariñas, Benito J

    2008-11-01

    Batch experiments were performed to study the inactivation kinetics of Mycobacterium avium in the presence of monochloramine at 5-30 degrees C, pH 6-10, and 0.30-42.3 mg Cl2/ L. For each temperature and pH investigated, limiting high and low inactivation rates were observed for high and low disinfectant concentrations, respectively, within the range investigated. The rate of inactivation transitioned from high to low over a relatively narrow range of intermediate monochloramine concentrations. The observed temperature dependence of inactivation was consistent with an Arrhenius expression with activation energies of 58.0 and 71.7 kJ/mol for the high and low concentration ranges, respectively. The rate of inactivation increased with decreasing pH, consistent with trends reported for the reaction of monochloramine with protein thiols. Experiments performed at pH approximately 3.5 showed that dichloramine was a weaker disinfectant than monochloramine, and that its contribution to the overall inactivation of M. avium with combined chlorine was negligible at pH 6-10. A kinetic model incorporating disinfectant concentration, temperature, and pH effects was used to illustrate that monochloramine efficiency to inactivate M. avium in water could vary broadly from adequate (e.g., 99.9% inactivation efficiency in 32 min at 5 mg Cl2/L, pH 6, 30 degrees C) to impractical (e.g., 99.9% inactivation efficiency in 9 d at 1 mg Cl2/L, pH 9, 5 degrees C).

  13. Mac-1 Regulates IL-13 Activity in Macrophages by Directly Interacting with IL-13Rα1.

    PubMed

    Cao, Chunzhang; Zhao, Juanjuan; Doughty, Emily K; Migliorini, Mary; Strickland, Dudley K; Kann, Maricel G; Zhang, Li

    2015-08-28

    Mac-1 exhibits a unique inhibitory activity toward IL-13-induced JAK/STAT activation and thereby regulates macrophage to foam cell transformation. However, the underlying molecular mechanism is unknown. In this study, we report the identification of IL-13Rα1, a component of the IL-13 receptor (IL-13R), as a novel ligand of integrin Mac-1, using a co-evolution-based algorithm. Biochemical analyses demonstrated that recombinant IL-13Rα1 binds Mac-1 in a purified system and supports Mac-1-mediated cell adhesion. Co-immunoprecipitation experiments revealed that endogenous Mac-1 forms a complex with IL-13Rα1 in solution, and confocal fluorescence microscopy demonstrated that these two receptors co-localize with each other on the surface of macrophages. Moreover, we found that genetic inactivation of Mac-1 promotes IL-13-induced JAK/STAT activation in macrophages, resulting in enhanced polarization along the alternative activation pathway. Importantly, we observed that Mac-1(-/-) macrophages exhibit increased expression of foam cell differentiation markers including 15-lipoxygenase and lectin-type oxidized LDL receptor-1 both in vitro and in vivo. Indeed, we found that Mac-1(-/-)LDLR(-/-) mice develop significantly more foam cells than control LDLR(-/-) mice, using an in vivo model of foam cell formation. Together, our data establish for the first time a molecular mechanism by which Mac-1 regulates the signaling activity of IL-13 in macrophages. This newly identified IL-13Rα1/Mac-1-dependent pathway may offer novel targets for therapeutic intervention in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Mac-1 Regulates IL-13 Activity in Macrophages by Directly Interacting with IL-13Rα1*

    PubMed Central

    Cao, Chunzhang; Zhao, Juanjuan; Doughty, Emily K.; Migliorini, Mary; Strickland, Dudley K.; Kann, Maricel G.; Zhang, Li

    2015-01-01

    Mac-1 exhibits a unique inhibitory activity toward IL-13-induced JAK/STAT activation and thereby regulates macrophage to foam cell transformation. However, the underlying molecular mechanism is unknown. In this study, we report the identification of IL-13Rα1, a component of the IL-13 receptor (IL-13R), as a novel ligand of integrin Mac-1, using a co-evolution-based algorithm. Biochemical analyses demonstrated that recombinant IL-13Rα1 binds Mac-1 in a purified system and supports Mac-1-mediated cell adhesion. Co-immunoprecipitation experiments revealed that endogenous Mac-1 forms a complex with IL-13Rα1 in solution, and confocal fluorescence microscopy demonstrated that these two receptors co-localize with each other on the surface of macrophages. Moreover, we found that genetic inactivation of Mac-1 promotes IL-13-induced JAK/STAT activation in macrophages, resulting in enhanced polarization along the alternative activation pathway. Importantly, we observed that Mac-1−/− macrophages exhibit increased expression of foam cell differentiation markers including 15-lipoxygenase and lectin-type oxidized LDL receptor-1 both in vitro and in vivo. Indeed, we found that Mac-1−/−LDLR−/− mice develop significantly more foam cells than control LDLR−/− mice, using an in vivo model of foam cell formation. Together, our data establish for the first time a molecular mechanism by which Mac-1 regulates the signaling activity of IL-13 in macrophages. This newly identified IL-13Rα1/Mac-1-dependent pathway may offer novel targets for therapeutic intervention in the future. PMID:26160172

  15. MacIntyre, Rival Traditions and Education

    ERIC Educational Resources Information Center

    Stolz, Steven A.

    2016-01-01

    This paper critically discusses MacIntyre's thesis that education is essentially a contested concept. In order to contextualise my discussion, I discuss both whether rival educational traditions of education found in MacIntyre's work--which I refer to as instrumental and non-instrumental justifications of education--can be rationally resolved…

  16. MacIntyre, Rival Traditions and Education

    ERIC Educational Resources Information Center

    Stolz, Steven A.

    2016-01-01

    This paper critically discusses MacIntyre's thesis that education is essentially a contested concept. In order to contextualise my discussion, I discuss both whether rival educational traditions of education found in MacIntyre's work--which I refer to as instrumental and non-instrumental justifications of education--can be rationally resolved…

  17. George MacDonald's Estimate of Childhood

    ERIC Educational Resources Information Center

    Pridmore, John

    2007-01-01

    The nineteenth-century fantasy writer George MacDonald believed that "it is better to be a child in a green field than a knight of many orders." In this paper, I shall explore the bearing of this high estimate of childhood on spiritual education. MacDonald explores the spirituality of the child in his essay "A Sketch of Individual Development" and…

  18. Identification and characterization of an immunogenic 22 kDa exported protein of Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Dupont, Chris; Thompson, Keith; Heuer, Cord; Gicquel, Brigitte; Murray, Alan

    2005-11-01

    An exported 22 kDa putative lipoprotein was identified in an alkaline phosphatase gene fusion library of Mycobacterium avium subsp. paratuberculosis and expressed in Mycobacterium smegmatis. The full nucleic acid sequence of the gene encoding P22 was determined and the ORF was cloned into a mycobacterial expression vector, enabling full-length P22 to be produced as a C-terminal polyhistidine-tagged protein in M. smegmatis. N-terminal sequencing of the recombinant protein confirmed cleavage of a signal sequence. Native P22 was detected in culture supernatants and cell sonicates of M. avium subsp. paratuberculosis strain 316F using rabbit antibody raised to recombinant P22. Investigation of the presence of similar genes in other mycobacterial species revealed that the gene was present in Mycobacterium avium subsp. avium and similar genes existed in Mycobacterium intracellulare and Mycobacterium scrofulaceum. Database searches showed that P22 belonged to the LppX/LprAFG family of mycobacterial lipoproteins also found in Mycobacterium leprae and in members of the Mycobacterium tuberculosis complex. P22 shared less than 75% identity to these proteins. Recombinant P22 was able to elicit interferon-gamma secretion in blood from eight of a group of nine sheep vaccinated with a live attenuated strain of M. avium subsp. paratuberculosis (strain 316F) compared to none from a group of five unvaccinated sheep. Antibody to P22 was detected by Western blot analysis in 10 out of 11 vaccinated sheep, in two out of two clinically affected cows and in 11 out of 13 subclinically infected cows.

  19. Cryptosporidium avium n. sp. (Apicomplexa: Cryptosporidiidae) in birds

    PubMed Central

    Holubová, Nikola; Sak, Bohumil; Horčičková, Michaela; Hlásková, Lenka; Květoňová, Dana; Menchaca, Sarah; McEvoy, John; Kváč, Martin

    2016-01-01

    The morphological, biological, and molecular characteristics of Cryptosporidium avian genotype V are described, and the species name Cryptosporidium avium is proposed to reflect its specificity for birds under natural and experimental conditions. Oocysts of C. avium measured 5.30–6.90 μm (mean = 6.26 μm) × 4.30–5.50 μm (mean = 4.86 μm) with a length to width ratio of 1.29 (1.14–1.47). Oocysts of C. avium obtained from four naturally infected red-crowned parakeets (Cyanoramphus novaezealandiae) were infectious for 6-month-old budgerigars (Melopsittacus undulatus) and hens (Gallus gallus f. domestica). The prepatent periods in both susceptible bird species was 11 days post infection (DPI). The infection intensity of C. avium in budgerigars and hens was low, with a maximum intensity of 5,000 oocysts per gram of faeces. Oocysts of C. avium were microscopically detected at only 12–16 DPI in hens and 12 DPI in budgerigars, while PCR analyses revealed the presence of specific DNA in faecal samples from 11 to 30 DPI (the conclusion of the experiment). Cryptosporidium avium was not infectious for 8-week-old SCID and BALB/c mice (Mus musculus). Naturally or experimentally infected birds showed no clinical signs of cryptosporidiosis and no pathology was detected. Developmental stages of C. avium were detected in the ileum and caecum using scanning electron microscopy. Phylogenetic analyses based on small subunit rRNA, actin, and heat shock protein 70 gene sequences revealed that C. avium is genetically distinct from previously described Cryptosporidium species. PMID:26905074

  20. Evaluation of quantitative polymerase chain reaction assays targeting Mycobacterium avium, M. intracellulare, and M. avium subspecies paratuberculosis in drinking water biofilms.

    PubMed

    Chern, Eunice C; King, Dawn; Haugland, Richard; Pfaller, Stacy

    2015-03-01

    Mycobacterium avium (MA), Mycobacterium intracellulare (MI), and Mycobacterium avium subsp. paratuberculosis (MAP) are difficult to culture due to their slow growing nature. A quantitative polymerase chain reaction (qPCR) method for the rapid detection of MA, MI, and MAP can be used to provide data supporting drinking water biofilms as potential sources of human exposure. The aim of this study was to characterize two qPCR assays targeting partial 16S rRNA gene sequences of MA and MI and use these assays, along with two previously reported MAP qPCR assays (IS900 and Target 251), to investigate Mycobacterium occurrence in kitchen faucet biofilms. MA and MI qPCR assays demonstrated 100% specificity and sensitivity when evaluated against 18 non-MA complex, 76 MA, and 17 MI isolates. Both assays detected approximately 1,000 cells from a diluted cell stock inoculated on a sampling swab 100% of the time. DNA analysis by qPCR indicated that 35.3, 56.9 and 11.8% of the 51 kitchen faucet biofilm samples collected contained MA, MI, and MAP, respectively. This study introduces novel qPCR assays designed to specifically detect MA and MI in biofilm. Results support the use of qPCR as an alternative to culture for detection and enumeration of MA, MI, and MAP in microbiologically complex samples.

  1. Fast arithmetic in MacLISP

    NASA Technical Reports Server (NTRS)

    Steele, G. L., Jr.

    1977-01-01

    MacLISP provides a compiler which produces numerical code competitive in speed with some FORTRAN implementations and yet compatible with the rest of the MacLISP system. All numerical programs can be run under the MacLISP interpreter. Additional declarations to the compiler specify type information which allows the generation of optimized numerical code which generally does not require the garbage collection of temporary numerical results. Array accesses are almost as fast as in FORTRAN, and permit the use of dynamically allocated arrays of varying dimensions. The implementation decisions regarding user interface, data representations, and interfacing conventions are discussed which allow the generation of fast numerical LISP code.

  2. User's manual for MacPASCO

    NASA Technical Reports Server (NTRS)

    Lucas, S. H.; Davis, R. C.

    1992-01-01

    A user's manual is presented for MacPASCO, which is an interactive, graphic, preprocessor for panel design. MacPASCO creates input for PASCO, an existing computer code for structural analysis and sizing of longitudinally stiffened composite panels. MacPASCO provides a graphical user interface which simplifies the specification of panel geometry and reduces user input errors. The user draws the initial structural geometry and reduces user input errors. The user draws the initial structural geometry on the computer screen, then uses a combination of graphic and text inputs to: refine the structural geometry; specify information required for analysis such as panel load and boundary conditions; and define design variables and constraints for minimum mass optimization. Only the use of MacPASCO is described, since the use of PASCO has been documented elsewhere.

  3. MACS as a tool for international inspections

    SciTech Connect

    Curtiss, J.A.; Indusi, J.P.

    1995-08-01

    The MACS/ACRS (Managed Access by Controlled Sensing/Access by Controlled Remote Sensing) system is a collection of communication devices, video capability, and distance-measuring equipment which can effectively substitute for the physical presence of a challenge inspector within a facility. The MACS design allows growth of the prototype, developed in response to the Chemical Weapons Convention (CWC), into a versatile device for inspection of sensitive nuclear facilities under other international arrangements, for example the proposed Fissile Material Cutoff Convention. A MACS/ACRS-type system in a standard, international-recognized configuration could resolve sensitive information and safety concerns through providing a means of achieving the goals of an inspection while excluding the inspector. We believe the technology used to develop MACS for the Defense Nuclear Agency, followed by ACRS for the Department of Energy, is universally adaptable for minimally-intrusive managed-access international inspections of sensitive sites.

  4. Cleanup MAC and MBA code ATP

    SciTech Connect

    Russell, V.K.

    1994-10-17

    The K Basins Materials Accounting (MAC) and Material Balance (MBA) database system had some minor code cleanup performed to its code. This ATP describes how the code was to be tested to verify its correctness.

  5. Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine

    PubMed Central

    Harris, N. Beth; Barletta, Raúl G.

    2001-01-01

    Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the etiologic agent of a severe gastroenteritis in ruminants known as Johne's disease. Economic losses to the cattle industry in the United States are staggering, reaching $1.5 billion annually. A potential pathogenic role in humans in the etiology of Crohn's disease is under investigation. In this article, we review the epidemiology, pathogenesis, diagnostics, and disease control measures of this important veterinary pathogen. We emphasize molecular genetic aspects including the description of markers used for strain identification, diagnostics, and phylogenetic analysis. Recent important advances in the development of animal models and genetic systems to study M. paratuberculosis virulence determinants are also discussed. We conclude with proposals for the applications of these models and recombinant technology to the development of diagnostic, control, and therapeutic measures. PMID:11432810

  6. MAC-awake of sevoflurane in children.

    PubMed

    Davidson, Andrew J; Wong, Aaron; Knottenbelt, Graham; Sheppard, Suzette; Donath, Susan; Frawley, Geoff

    2008-08-01

    Age influences the potency of anesthetic agents, but there is little information on how age influences MAC-awake. MAC-awake may be an important aspect of anesthesia potency for the prevention of awareness during anesthesia. The aim of this study was to measure MAC-awake in a range of ages in children. After institutional ethics approval and informed parental consent 60 children were enrolled; 20 in each of three age groups (2 to <5, 5 to <8 and 8-12 years). Children were excluded if they had opioids, sedative premedication or a procedure likely to cause any residual discomfort. All children had sevoflurane anesthesia. At the end of the procedure the sevoflurane was decreased to the target concentration. Once the target endtidal concentration was achieved it was maintained for 10 min before a standard stimulus was applied and an observer determined if the child was awake. The Dixon up-down method was used to determine progression of subsequent concentrations and MAC-awake (ED50) for the three age groups were obtained using the probit model. This study found evidence for a difference in ED50 between age groups (P = 0.008). The MAC-awake was highest in the youngest group (0.66%) and similar in the older groups (0.45% and 0.43%). Although MAC-awake changes with age, in the ages where awareness has been reported, MAC-awake was found to be relatively low, and therefore it seems unlikely that age-specific changes to MAC-awake are a cause for awareness in children aged 5-12 years.

  7. 42 CFR 423.2118 - Obtaining evidence from the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Obtaining evidence from the MAC. 423.2118 Section..., MAC review, and Judicial Review § 423.2118 Obtaining evidence from the MAC. An enrollee may request... the costs of providing these items. If an enrollee requests evidence from the MAC and an opportunity...

  8. 42 CFR 423.1974 - Medicare Appeals Council (MAC) review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Medicare Appeals Council (MAC) review. 423.1974..., MAC review, and Judicial Review § 423.1974 Medicare Appeals Council (MAC) review. An enrollee who is dissatisfied with an ALJ hearing decision may request that the MAC review the ALJ's decision or dismissal as...

  9. 42 CFR 423.2130 - Effect of the MAC's decision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Effect of the MAC's decision. 423.2130 Section 423... (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2130 Effect of the MAC's decision. The MAC's decision is final and binding...

  10. 42 CFR 423.2120 - Filing briefs with the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Filing briefs with the MAC. 423.2120 Section 423... (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2120 Filing briefs with the MAC. Upon request, the MAC will give the...

  11. 42 CFR 405.1130 - Effect of the MAC's decision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Effect of the MAC's decision. 405.1130 Section 405....1130 Effect of the MAC's decision. The MAC's decision is final and binding on all parties unless a Federal district court issues a decision modifying the MAC's decision or the decision is revised as the...

  12. 42 CFR 405.1120 - Filing briefs with the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Filing briefs with the MAC. 405.1120 Section 405....1120 Filing briefs with the MAC. Upon request, the MAC will give the party requesting review, as well... ending with the date the brief is received by the MAC will not be counted toward the adjudication...

  13. 42 CFR 423.2126 - Case remanded by the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Case remanded by the MAC. 423.2126 Section 423.2126... (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2126 Case remanded by the MAC. (a) When the MAC may remand a case to the ALJ...

  14. AeroMACS system characterization and demonstrations

    NASA Astrophysics Data System (ADS)

    Kerczewski, R. J.; Apaza, R. D.; Dimond, R. P.

    This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  15. AeroMACS System Characterization and Demonstrations

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

    2013-01-01

    The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past three years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  16. AeroMACS System Characterization and Demonstrations

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Apaza, Rafael D.; Dimond, Robert P.

    2013-01-01

    This The Aeronautical Mobile Airport Communications System (AeroMACS) is being developed to provide a new broadband wireless communications capability for safety critical communications in the airport surface domain, providing connectivity to aircraft and other ground vehicles as well as connections between other critical airport fixed assets. AeroMACS development has progressed from requirements definition through technology definition, prototype deployment and testing, and now into national and international standards development. The first prototype AeroMACS system has been deployed at the Cleveland Hopkins International Airport (CLE) and the adjacent NASA Glenn Research Center (GRC). During the past 3 years, extensive technical testing has taken place to characterize the performance of the AeroMACS prototype and provide technical support for the standards development process. The testing has characterized AeroMACS link and network performance over a variety of conditions for both fixed and mobile data transmission and has included basic system performance testing and fixed and mobile applications testing. This paper provides a summary of the AeroMACS performance testing and the status of standardization activities that the testing supports.

  17. Evaluation of Subspecies-specific Proteins for the Diagnosis of Mycobacterium avium subspecies paratuberculosis Infections

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subspecies paratuberculosis (Map)-specific proteins (35) were identified by comparing the proteomes of Map isolates with those of the genetically similar subspecies IS901+ Mycobacterium avium subspecies avium or silvaticum. This approach identified subspecies-specific proteins in...

  18. A Gene Specific to Mycobacterium avium subsp. paratuberculosis, But Only at the Transcription-translation Level

    USDA-ARS?s Scientific Manuscript database

    There is no known antibody that detects M. avium subsp paratuberculosis and does not cross react with other M. avium subspecies. In the present study, a monoclonal antibody was identified from mice immunized with a cell membrane fraction of M. avium subsp paratuberculosis strain K-10. This antibod...

  19. Comparative Genomic Analysis of Mycobacterium avium subspecies Obtained from Multiple Host Species

    USDA-ARS?s Scientific Manuscript database

    A comparative genomic approach was used to identify large sequence polymorphisms among Mycobacterium avium (M. avium) subspecies obtained from a variety of host animals. DNA microarrays were used as a platform for comparing mycobacterial isolates with the sequenced bovine isolate M. avium subsp. p...

  20. TGF-β-Mediated Sustained ERK1/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates

    PubMed Central

    L'Abbate, Carolina; Cipriano, Ivone; Pérez-Hurtado, Elizabeth Cristina; Leão, Sylvia Cardoso; Carneiro, Célia Regina Whitaker; Machado, Joel

    2011-01-01

    Transforming growth factor beta (TGF-β) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-β production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-β and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-β produced by ECs are sufficient to induce a self-sustaining autocrine TGF-β signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-β to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-β receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-β produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-β receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-β production. In summary, our findings indicate that the amplitude of TGF-β signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth. PMID:21731758

  1. Bordetella avium Antibiotic Resistance, Novel Enrichment Culture, and Antigenic Characterization

    PubMed Central

    Beach, Nathan M.; Thompson, Seth; Mutnick, Rachel; Brown, Lisa; Kettig, Gina; Puffenbarger, Robyn; Miyamoto, David; Temple, Louise

    2012-01-01

    Bordetella avium continues to be an economic issue in the turkey industry as the causative agent of bordetellosis, which often leads to serious secondary infections. This study presents a broad characterization of the antibiotic resistance patterns in this diverse collection of B. avium strains collected over the past thirty years. In addition, the plasmid basis for the antibiotic resistance was characterized. The antibiotic resistance pattern allowed the development of a novel enrichment culture method that was subsequently employed to gather new isolates from diseased turkeys and a healthy sawhet owl. While a healthy turkey flock was shown to seroconvert by four weeks-of-age, attempts to culture B. avium from healthy turkey poults were unsuccessful. Western blot of B. avium strains using pooled serum from diseased and healthy commercial turkey flocks revealed both antigenic similarities and differences between strains. In sum, the work documents the continued exposure of commercial turkey flocks to B. avium and the need for development of an effective, inexpensive vaccine to control spread of the disease. PMID:22721730

  2. Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages.

    PubMed

    Bermudez, Luiz E; Danelishvili, Lia; Babrack, Lmar; Pham, Tuan

    2015-01-01

    Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacteria that infects immunocompromised humans. MAH cases are increasing in incidence, making it crucial to gain knowledge of the pathogenic mechanisms associated with the bacterium. MAH infects macrophages and after several days the infection triggers the phagocyte apoptosis. Many of the intracellular MAH escape the cell undergoing apoptosis leading to infection of neighboring macrophages. We screened a transposon bank of MAH mutants in U937 mononuclear phagocytes for the inability to escape macrophages undergoing apoptosis. Mutations in genes; MAV_2235, MAV_2120, MAV_2410, and MAV_4563 resulted in the inability of the bacteria to exit macrophages upon apoptosis. Complementation of the mutations corrected the phenotype either completely or partially. Testing for the ability of the mutants to survive in macrophages compared to the wild-type bacterium revealed that the mutant clones were not attenuated up to 4 days of infection. Testing in vivo, however, demonstrated that all the MAH clones were attenuated compared with the wild-type MAC 104 in tissues of mice. Although the mechanism associated with the bacterial inability to leave apoptotic macrophages is unknown, the identification of macrophage cytoplasm targets for the MAH proteins suggest that they interfere either with protein degradation machinery or post-translation mechanisms. The identification of tatC as a MAH protein involved in the ability of MAH to leave macrophages, suggests that secreted effector(s) are involved in the process. The study reveals a pathway of escape from macrophages, not shared with Mycobacterium tuberculosis.

  3. Numerical taxonomy of mycobactin-dependent mycobacteria, emended description of Mycobacterium avium, and description of Mycobacterium avium subsp. avium subsp. nov., Mycobacterium avium subsp. paratuberculosis subsp. nov., and Mycobacterium avium subsp. silvaticum subsp. nov.

    PubMed

    Thorel, M F; Krichevsky, M; Lévy-Frébault, V V

    1990-07-01

    We performed a numerical taxonomy analysis of 38 Mycobacterium paratuberculosis and related mycobacterial strains, including wood pigeon mycobacteria; this analysis was based on 22 tests, which were selected for their potential discriminative value from a total of 51 tests studied and produced four well-defined clusters. Cluster 1 contained the M. paratuberculosis strains, including two strains isolated from Crohn's disease patients; cluster 2 contained Mycobacterium avium and Mycobacterium intracellulare reference strains; cluster 3 consisted of the wood pigeon mycobacteria; and the only strain in cluster 4 was M. paratuberculosis 316F, which is used for antigen and vaccine production. Strains in cluster 1 were mycobactin dependent even when they were subcultured, whereas strains in cluster 3 were unable to grow on egg medium and their growth was stimulated by pH 5.5. Growth stimulation by pyruvate, resistance to D-cycloserine (50 micrograms/ml), and alkaline phosphatase activity also were characteristics that were useful for discriminating between clusters 1 and 3. The results of previous DNA-DNA hybridization studies have demonstrated that M. avium Chester 1901, M. paratuberculosis Bergey et al. 1923, and the wood pigeon mycobacteria belong to a single genomic species, and we propose that the name of this species should be M. avium. On the basis of the results of previous genomic analyses based on restriction fragment length, the results of polymorphism studies, and DNA patterns determined by field inversion gel electrophoresis as well as the results of our phenotypic study, we propose that the species should be divided into subspecies which correspond to pathogenicity and host range characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Concentration of Mycobacterium avium by hospital hot water systems.

    PubMed

    du Moulin, G C; Stottmeier, K D; Pelletier, P A; Tsang, A Y; Hedley-Whyte, J

    1988-09-16

    Water from 34 sites on two temporarily vacant hospital floors was analyzed for the presence of mycobacteria. These sites included 18 cold water taps and 16 hot water taps, including shower heads. A total of 14 sites (41%) demonstrated the presence of Mycobacterium avium as confirmed by biochemical characterization, DNA/rRNA probe analysis, and seroagglutination. Of positive sites, 11 were hot water sources with an average temperature of 55 degrees C and yielding up to 500 colony-forming units per 100 mL. Seven of 11 strains analyzed for glycolipid antigens were identified with the type 4 serovar, the preponderant serovar of M avium in patients with acquired immunodeficiency syndrome from the Boston area. Potable hot water systems, particularly those that generate aerosols, may contain concentrations of M avium greater than those found in cold water systems and could serve as an environmental source for colonization and infection of immunocompromised persons.

  5. Chlorine, Chloramine, Chlorine Dioxide, and Ozone Susceptibility of Mycobacterium avium

    PubMed Central

    Taylor, Robert H.; Falkinham, Joseph O.; Norton, Cheryl D.; LeChevallier, Mark W.

    2000-01-01

    Environmental and patient isolates of Mycobacterium avium were resistant to chlorine, monochloramine, chlorine dioxide, and ozone. For chlorine, the product of the disinfectant concentration (in parts per million) and the time (in minutes) to 99.9% inactivation for five M. avium strains ranged from 51 to 204. Chlorine susceptibility of cells was the same in washed cultures containing aggregates and in reduced aggregate fractions lacking aggregates. Cells of the more slowly growing strains were more resistant to chlorine than were cells of the more rapidly growing strains. Water-grown cells were 10-fold more resistant than medium-grown cells. Disinfectant resistance may be one factor promoting the persistence of M. avium in drinking water. PMID:10742264

  6. Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype.

    PubMed

    Abendaño, Naiara; Sevilla, Iker A; Prieto, José Miguel; Garrido, Joseba M; Juste, Ramon A; Alonso-Hearn, Marta

    2013-05-03

    Assessment of the virulence of isolates of Mycobacterium avium subsp. paratuberculosis (Map) exhibiting distinct genotypes and isolated from different hosts may help to clarify the degree to which clinical manifestations of the disease in cattle can be attributed to bacterial or to host factors. The objective of this study was to test the ability of 10 isolates of Map representing distinct genotypes and isolated from domestic (cattle, sheep, and goat), and wildlife animal species (fallow deer, deer, wild boar, and bison) to enter and grow in bovine macrophages. The isolates were previously typed using IS1311 PCR followed by restriction endonuclease analysis into types C, S or B. Intracellular growth of the isolates in a bovine macrophage-like cell line (BoMac) and in primary bovine monocyte-derived macrophages (MDM) was evaluated by quantification of CFU numbers in the initial inoculum and inside of the host cells at 2h and 7 d p.i. using an automatic liquid culture system (Bactec MGIT 960). Individual data illustrated that growth was less variable in BoMac than in MDM cells. All the isolates from goat and sheep hosts persisted within BoMac cells in lower CFU numbers than the other tested isolates after 7 days of infection regardless of genotype. In addition, BoMac cells exhibited differential inflammatory, apoptotic and destructive responses when infected with a bovine or an ovine isolate; which correlated with the differential survival of these strains within BoMac cells. Our results indicated that the survival of the tested Map isolates within bovine macrophages is associated with the specific host from which the isolates were initially isolated.

  7. BFT replication resistant to MAC attacks

    NASA Astrophysics Data System (ADS)

    Zbierski, Maciej

    2016-09-01

    Over the last decade numerous Byzantine fault-tolerant (BFT) replication protocols have been proposed in the literature. However, the vast majority of these solutions reuse the same authentication scheme, which makes them susceptible to a so called MAC attack. Such vulnerability enables malicious clients to undetectably prevent the replicated service from processing incoming client requests, and consequently making it permanently unavailable. While some BFT protocols attempted to address this issue by using different authentication mechanisms, they at the same time significantly degraded the performance achieved in correct environments. This article presents a novel adaptive authentication mechanism which can be combined with practically any Byzantine fault-tolerant replication protocol. Unlike previous solutions, the proposed scheme dynamically switches between two operation modes to combine high performance in correct environments and liveness during MAC attacks. The experiment results presented in the article demonstrate that the proposed mechanism can sufficiently tolerate MAC attacks without introducing any observable overhead whenever no faults are present.

  8. Preservation of monocyte effector functions against Mycobacterium avium-M. intracellulare in patients with AIDS.

    PubMed Central

    Johnson, J L; Shiratsuchi, H; Toba, H; Ellner, J J

    1991-01-01

    Mycobacterium avium-M. intracellulare is a frequent cause of late disseminated infection in patients with AIDS. The ability of human peripheral blood monocytes to phagocytose and kill M. avium was examined in an in vitro model. Monocytes were obtained from 13 healthy volunteers and 11 patients with AIDS, three of whom had documented disseminated M. avium infection. Monocytes were precultured for 2 days before infection with two AIDS-associated and two non-AIDS-associated strains of M. avium. Uptake of M. avium as measured by counting intracellular acid-fast bacilli did not differ among healthy subjects, patients with AIDS, or patients with AIDS and previously documented disseminated M. avium infection. Intracellular growth of M. avium was examined by a CFU assay of cell lysates from M. avium-infected monocytes after 0, 4, and 7 days of culture. Intracellular growth inhibition of M. avium at 7 days after infection was comparable between patients with AIDS and healthy donors for all M. avium strains tested. The effects of the addition of recombinant gamma interferon on M. avium uptake and intracellular growth in monocytes also were studied. Pretreatment of monocytes with gamma interferon prior to infection suppressed monocyte phagocytosis of M. avium. Continuously coculturing of monocytes with gamma interferon after infection augmented killing of M. avium among both patients with AIDS and healthy controls for three of the four strains of M. avium tested. The magnitude of this effect, however, was variable from donor to donor and strain to strain. No significant differences were noted between the growth-inhibiting abilities of gamma-interferon-treated monocytes obtained from healthy volunteers and those obtained from patients with AIDS. PMID:1910011

  9. Cryopreservation of Prunus avium L. embryogenic tissues.

    PubMed

    Grenier-de March, Ghislaine; de Boucaud, Marie-Therese; Chmielarz, Pawel

    2005-01-01

    Embryogenic tissues from wild cherry (Prunus avium L.) were successfully cryopreserved by using a one-step freezing procedure. Cryoprotection consisted of a pretreatment on solid medium with increasing sucrose concentrations (0.25 M for 1 day, 0.5 M for 1 day, 0.75 M for 2 days, and 1.0 M for 3 days), followed by air desiccation to about 20 percent moisture content (fresh weight basis). This method was compared with a pretreatment on solid medium containing 5 percent DMSO and 2 percent proline, followed by immersion in a modified PVS2 cryoprotective solution. Pretreatment on solid medium with increasing concentrations of sucrose led to regrowth of frozen embryogenic tissues, and after 6 weeks of culture, growth was comparable to that of non-dehydrated and non-frozen tissues. By contrast, no regrowth was observed when embryogenic tissues were submitted to the solid/liquid pretreatment with DMSO/proline and a modified PVS2 solution.

  10. Optimal sensor placement for maximum area coverage (MAC) for damage localization in composite structures

    NASA Astrophysics Data System (ADS)

    Thiene, M.; Sharif Khodaei, Z.; Aliabadi, M. H.

    2016-09-01

    In this paper an optimal sensor placement algorithm for attaining the maximum area coverage (MAC) within a sensor network is presented. The proposed novel approach takes into account physical properties of Lamb wave propagation (attenuation profile, direction dependant group velocity due to material anisotropy) and geometrical complexities (boundary reflections, presence of openings) of the structure. A feature of the proposed optimization approach lies in the fact that it is independent of characteristics of the damage detection algorithm (e.g. probability of detection) making it readily up-scalable to large complex composite structures such as aircraft stiffened composite panel. The proposed fitness function (MAC) is independent of damage parameters (type, severity, location). Statistical analysis carried out shows that the proposed optimum sensor network with MAC results in high probability of damage localization. Genetic algorithm is coupled with the fitness function to provide an efficient optimization strategy.

  11. The Leishmania donovani histidine acid ecto-phosphatase LdMAcP: insight into its structure and function

    PubMed Central

    Papadaki, Amalia; Politou, Anastasia S.; Smirlis, Despina; Kotini, Maria P.; Kourou, Konstadina; Papamarcaki, Thomais; Boleti, Haralabia

    2015-01-01

    Acid ecto-phosphatase activity has been implicated in Leishmania donovani promastigote virulence. In the present study, we report data contributing to the molecular/structural and functional characterization of the L. donovani LdMAcP (L. donovani membrane acid phosphatase), member of the histidine acid phosphatase (HAcP) family. LdMAcP is membrane-anchored and shares high sequence identity with the major secreted L. donovani acid phosphatases (LdSAcPs). Sequence comparison of the LdMAcP orthologues in Leishmania sp. revealed strain polymorphism and species specificity for the L. donovani complex, responsible for visceral leishmaniasis (Khala azar), proposing thus a potential value of LdMAcP as an epidemiological or diagnostic tool. The extracellular orientation of the LdMAcP catalytic domain was confirmed in L. donovani promastigotes, wild-type (wt) and transgenic overexpressing a recombinant LdMAcP–mRFP1 (monomeric RFP1) chimera, as well as in transiently transfected mammalian cells expressing rLdMAcP–His. For the first time it is demonstrated in the present study that LdMAcP confers tartrate resistant acid ecto-phosphatase activity in live L. donovani promastigotes. The latter confirmed the long sought molecular identity of at least one enzyme contributing to this activity. Interestingly, the L. donovani rLdMAcP–mRFP1 promastigotes generated in this study, showed significantly higher infectivity and virulence indexes than control parasites in the infection of J774 mouse macrophages highlighting thereby a role for LdMAcP in the parasite's virulence. PMID:25695743

  12. Mission-Adaptable Chemical Sensor (MACS)

    DTIC Science & Technology

    2009-03-27

    Surrogate Software ......................................................................... 75 9 Basic System Integration and Packaging ...78 9.1 Architecture of the Packaging for the MACS Phase 1 Systems (1 and 2...responsible for adapting laboratory scale technologies into a very small package . In general, ST leads the systems engineering and central electronics; OSU

  13. MacIntyre, Managerialism and Universities

    ERIC Educational Resources Information Center

    Stolz, Steven A.

    2017-01-01

    MacIntyre's earlier work and concern with social science enquiry not only exposes its limits, but also provides an insight into how its knowledge claims have been put to ideological use. He maintains that the institutional embodiment of these ideological ideas is the bureaucratic manager who has had a negative role to play in social structures…

  14. MacIntyre, Managerialism and Universities

    ERIC Educational Resources Information Center

    Stolz, Steven A.

    2017-01-01

    MacIntyre's earlier work and concern with social science enquiry not only exposes its limits, but also provides an insight into how its knowledge claims have been put to ideological use. He maintains that the institutional embodiment of these ideological ideas is the bureaucratic manager who has had a negative role to play in social structures…

  15. Lifetime tests for MAC vertex chamber

    SciTech Connect

    Nelson, H.N.

    1986-07-01

    A vertex chamber for MAC was proposed to increase precision in the measurement of the B hadron and tau lepton lifetimes. Thin-walled aluminized mylar drift tubes were used for detector elements. A study of radiation hardness was conducted under the conditions of the proposed design using different gases and different operating conditions. (LEW)

  16. Managed Access by Controlled Sensing (MACS)

    SciTech Connect

    Curtiss, J.A.; Indusi, J.P.

    1994-08-01

    During chemical weapons challenge inspections, the CWC treaty allows ``alternate means`` of access to be proposed by the nation challenged. BNL`s Safeguards, Safety and Nonproliferation Division is funded by the Defense Nuclear Agency to develop a system to provide the challenge inspection team with a ``virtual presence`` within the facility while denying personal access. A general purpose configuration of a mobile station manned by site personnel and a base station manned by the challenge inspector, supported by a flexible communication system, will allow facility personnel to tailor the basic model to their site. Design of the MACS system is based on maximum use of commercial equipment that is available on the international market. Design requirements for the MACS system include methods of establishing geographical position, distance measuring equipment for use in verifying dimensions on floor plans, video and two-way audio links between the mobile unit and the base station, and portability and versatility of the equipment. The MACS platform will also support deployment of selected instrumentation which the site may offer to the challenge inspection team. This paper describes the design and construction of the prototype MACS system.

  17. Rapid broth macrodilution method for determination of MICs for Mycobacterium avium isolates.

    PubMed Central

    Siddiqi, S H; Heifets, L B; Cynamon, M H; Hooper, N M; Laszlo, A; Libonati, J P; Lindholm-Levy, P J; Pearson, N

    1993-01-01

    A multicenter study was done to investigate the accuracy and reproducibility of a method for determining the MICs of antimicrobial agents against the Mycobacterium avium complex in 7H12 broth with the BACTEC system. In phase I, with eight drugs and 10 strains, intralaboratory reproducibility was 95.7 to 100%, allowing a 1-dilution difference upon repeat testing. The results of phase II testing with 41 additional strains were consistent with those obtained in phase I, with good interlaboratory reproducibility. The radiometric method was validated by sampling and plating of the same broth cultures and determining, by the number of CFU per milliliter, the lowest drug concentration that inhibited more than 99% of the initial bacterial population. Three test concentrations of each drug and the tentative interpretation of results are proposed. Radiometric MIC determination has the potential to become the method of choice for clinical microbiology laboratories and evaluation of new agents for the treatment of M. avium infections, both pulmonary and disseminated. Images PMID:8408551

  18. High-Density Lipoprotein Binds to Mycobacterium avium and Affects the Infection of THP-1 Macrophages

    PubMed Central

    Ichimura, Naoya; Sato, Megumi; Yoshimoto, Akira; Yano, Kouji; Ohkawa, Ryunosuke; Kasama, Takeshi

    2016-01-01

    High-density lipoprotein (HDL) is involved in innate immunity toward various infectious diseases. Concerning bacteria, HDL is known to bind to lipopolysaccharide (LPS) and to neutralize its physiological activity. On the other hand, cholesterol is known to play an important role in mycobacterial entry into host cells and in survival in the intracellular environment. However, the pathogenicity of Mycobacterium avium (M. avium) infection, which tends to increase worldwide, remains poorly studied. Here we report that HDL indicated a stronger interaction with M. avium than that with other Gram-negative bacteria containing abundant LPS. A binding of apolipoprotein (apo) A-I, the main protein component of HDL, with a specific lipid of M. avium might participate in this interaction. HDL did not have a direct bactericidal activity toward M. avium but attenuated the engulfment of M. avium by THP-1 macrophages. HDL also did not affect bacterial killing after ingestion of live M. avium by THP-1 macrophage. Furthermore, HDL strongly promoted the formation of lipid droplets in M. avium-infected THP-1 macrophages. These observations provide new insights into the relationship between M. avium infection and host lipoproteins, especially HDL. Thus, HDL may help M. avium to escape from host innate immunity. PMID:27516907

  19. Exposure histories of lunar meteorites - ALHA81005, MAC88104, MAC88105, and Y791197

    NASA Technical Reports Server (NTRS)

    Nishiizumi, K.; Arnold, J. R.; Klein, J.; Fink, D.; Middleton, R.; Kubik, P. W.; Sharma, P.; Elmore, D.; Reedy, R. C.

    1991-01-01

    The cosmogenic radionuclides Ca-41, Cl-36, Al-26, and Be-10 in the Allan Hills 81005, MacAlpine Hills 88104, MacAlpine Hills 88105, and Yamato 791197 meteorites were measured by accelerator mass spectrometry. Mn-53 in Allan Hills 81005 and Yamato 791197 was measured by neutron activation. These four lunar meteorites experienced similar histories. They were ejected from near the surface of the moon ranging in depth down to 400 g/sq cm and had very short transition times (less than 0.1 Ma) from the moon to the earth. A comparison of the cosmogenic nuclide concentrations in MacAlpine Hills 88104 and MacAlpine Hills 88105 clearly indicates that they are a pair from the same fall.

  20. Exposure histories of lunar meteorites - ALHA81005, MAC88104, MAC88105, and Y791197

    NASA Technical Reports Server (NTRS)

    Nishiizumi, K.; Arnold, J. R.; Klein, J.; Fink, D.; Middleton, R.; Kubik, P. W.; Sharma, P.; Elmore, D.; Reedy, R. C.

    1991-01-01

    The cosmogenic radionuclides Ca-41, Cl-36, Al-26, and Be-10 in the Allan Hills 81005, MacAlpine Hills 88104, MacAlpine Hills 88105, and Yamato 791197 meteorites were measured by accelerator mass spectrometry. Mn-53 in Allan Hills 81005 and Yamato 791197 was measured by neutron activation. These four lunar meteorites experienced similar histories. They were ejected from near the surface of the moon ranging in depth down to 400 g/sq cm and had very short transition times (less than 0.1 Ma) from the moon to the earth. A comparison of the cosmogenic nuclide concentrations in MacAlpine Hills 88104 and MacAlpine Hills 88105 clearly indicates that they are a pair from the same fall.

  1. MACS as a tool for international inspections

    SciTech Connect

    Curtiss, J.A.; Indusi, J.P.

    1995-06-01

    General acceptance of the challenge provision in the Chemical Weapons Convention has the potential for influence in other arms control areas. While most applications of the challenge inspection may be straightforward, there may be instances where access to the site by inspectors may be problematic. The MACS system described in this paper was developed to respond to these situations. Inspection and verification may be difficult when a host is unwilling,for valid reasons, to permit physical access to a site. We proposed a system of remote sensors which may be used to demonstrate compliance with Chemical Weapons Convention (CWC) challenge inspections even ff the inspector is physically excluded from a sensitive site. The system is based upon alternative-means-of-access provisions of the CWC. The Defense Nuclear Agency (DNA) funded design and construction of a system prototype, designated as MACS for Managed Access by Controlled Sensing. Features of the MACS design allow growth of the prototype into a versatile device for international monitoring of production facilities and other sites. MACS consists of instrumentation and communication equipment allowing site personnel to conduct a facility tour and perform acceptable measurements, while physically excluding the inspector from the facility. MACS consists of a base station used by the inspector, and a mobile unit used within the facility and manipulated by the facility staff. The base station and the mobile unit are @ed by a communication system, currently realized as a fiber optic cable. The mobile unit is equipped with television cameras and remote-reading distance-measuring equipment (DME) for use in verifying locations and dimensions. Global Positioning System receivers on the mobile unit provide both precise location and dead reckoning, suitable for tracking the mobile unit`s position while within a building when satellite signals are not available.

  2. 42 CFR 405.1126 - Case remanded by the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Case remanded by the MAC. 405.1126 Section 405.1126....1126 Case remanded by the MAC. (a) When the MAC may remand a case. Except as specified in § 405.1122(c), the MAC may remand a case in which additional evidence is needed or additional action by the ALJ is...

  3. First identification of Mycobacterium avium paratuberculosis sheep strain in Argentina.

    PubMed

    Travería, G E; Zumarraga, M; Etchechoury, I; Romano, M I; Cataldi, A; Pinedo, M F Alvarado; Pavlik, I; Pribylova, R; Romero, J R

    2013-01-01

    We here identified for the first time the presence of Mycobacterium avium paratuberculosis (MAP) sheep (S) strain in Argentina. IS900 polymerase chain reaction (PCR) was positive. The S strain was compared with MAP cattle (C) strains by using IS1311 PCR-restriction endonuclease analysis (PCR-REA), multiplex PCR and restriction fragment length polymorphism (RFLP) analysis.

  4. Cellular Interactions in Mycobacterium avium subsp. paratuberculosis Infection

    USDA-ARS?s Scientific Manuscript database

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Noted as one of the more fastidious mycobacteria, infection with MAP is often chara...

  5. Mycobacterium avium subsp. paratuberculosis infection, immunology and pathology of livestock

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subsp. paratuberculosis (MAP) infection in ruminants leads to a chronic and progressive enteric disease (Johne’s disease) that results in loss of intestinal function, poor body condition, and eventual death. Transmission is primarily through a fecal-oral route in neonates but con...

  6. Tuberculosis in Birds: Insights into the Mycobacterium avium Infections

    PubMed Central

    Dhama, Kuldeep; Mahendran, Mahesh; Tiwari, Ruchi; Dayal Singh, Shambhu; Kumar, Deepak; Singh, Shoorvir; Sawant, Pradeep Mahadev

    2011-01-01

    Tuberculosis, a List B disease of World Organization for Animal Health, caused by M. avium or M. genavense predominantly affects poultry and pet or captive birds. Clinical manifestations in birds include emaciation, depression and diarrhea along with marked atrophy of breast muscle. Unlike tuberculosis in animals and man, lesions in lungs are rare. Tubercular nodules can be seen in liver, spleen, intestine and bone marrow. Granulomatous lesion without calcification is a prominent feature. The disease is a rarity in organized poultry sector due to improved farm practices, but occurs in zoo aviaries. Molecular techniques like polymerase chain reaction combined with restriction fragment length polymorphism and gene probes aid in rapid identification and characterization of mycobacteria subspecies, and overcome disadvantages of conventional methods which are slow, labour intensive and may at times fail to produce precise results. M. avium subsp. avium with genotype IS901+ and IS1245+ causes infections in animals and human beings too. The bacterium causes sensitivity in cattle to the tuberculin test. The paper discusses in brief the M. avium infection in birds, its importance in a zoonotic perspective, and outlines conventional and novel strategies for its diagnosis, prevention and eradication in domestic/pet birds and humans alike. PMID:21776352

  7. Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.

    PubMed

    Mdluli, K; Swanson, J; Fischer, E; Lee, R E; Barry, C E

    1998-03-01

    Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.

  8. Characterization and expression of secA in Mycobacterium avium.

    PubMed

    Limia, A; Sangari, F J; Wagner, D; Bermudez, L E

    2001-04-13

    Mycobacterium avium is both a pathogen that infects several hosts such as humans, pigs, and birds, as well as a microorganism that is encountered in environmental sources (soil and water). Protein secretion by the bacterium is likely to influence its ability to overcome adverse and competitive conditions both within or outside the host. Using a combination of cloning and information available in the databank, we characterized the secA gene from M. avium, encoding for a major preprotein translocase subunit associated with the secretion system of prokaryotics. In addition, we cloned the secA promoter sequence in a reporter construct upstream of a promoterless gfp. It was determined that the secA of M. avium shares large homology with the secA of Mycobacterium tuberculosis but not with secA of Mycobacterium leprae. secA expression was determined to be greater at logarithmic growth phase although it was also expressed at low levels during the stationary phase. secA expression was also observed when the bacteria were incubated in water as well as within human monocyte-derived macrophages and in conditions that are associated with biofilm formation. Future evaluation of the sec pathway in M. avium might provide important information about secreted proteins that are required for survival in different environments.

  9. 42 CFR 422.608 - Medicare Appeals Council (MAC) review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Medicare Appeals Council (MAC) review. 422.608... and Appeals § 422.608 Medicare Appeals Council (MAC) review. Any party to the hearing, including the MA organization, who is dissatisfied with the ALJ hearing decision, may request that the MAC review...

  10. 42 CFR 405.1128 - Action of the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Action of the MAC. 405.1128 Section 405.1128 Public... the MAC. (a) After it has reviewed all the evidence in the administrative record and any additional evidence received, subject to the limitations on MAC consideration of additional evidence in § 405.1122...

  11. 42 CFR 423.2128 - Action of the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Action of the MAC. 423.2128 Section 423.2128 Public...) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2128 Action of the MAC. (a) After it has reviewed all the evidence in the...

  12. 42 CFR 405.1118 - Obtaining evidence from the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Obtaining evidence from the MAC. 405.1118 Section... Council Review § 405.1118 Obtaining evidence from the MAC. A party may request and receive a copy of all... these items. If a party requests evidence from the MAC and an opportunity to comment on that evidence...

  13. POD/MAC-Based Modal Basis Selection for a Reduced Order Nonlinear Response Analysis

    NASA Technical Reports Server (NTRS)

    Rizzi, Stephen A.; Przekop, Adam

    2007-01-01

    A feasibility study was conducted to explore the applicability of a POD/MAC basis selection technique to a nonlinear structural response analysis. For the case studied the application of the POD/MAC technique resulted in a substantial improvement of the reduced order simulation when compared to a classic approach utilizing only low frequency modes present in the excitation bandwidth. Further studies are aimed to expand application of the presented technique to more complex structures including non-planar and two-dimensional configurations. For non-planar structures the separation of different displacement components may not be necessary or desirable.

  14. Implementation of a reference management system, MacRefer, under HyperCard.

    PubMed

    Sato, H; Sato, S; Horikoshi, I

    1996-06-01

    We have developed a reference management system, MacRefer, using HyperTalk on Macintosh personal computers. Using this program, one can automatically acquire data from databases created by EndNote Plus and from OVID- or Medlar-formatted records downloaded via an online use of Medline. The MacRefer's capability of formatting bibliographic database in user-defined formats is comparable with the exemplified bibliography maker, EndNote Plus. Moreover, MacRefer has several competitive features, which are insufficiently equipped with EndNote Plus. For example, MacRefer is capable of (1) maintaining subsets within a database, (2) executing complex, structured searches combining up to nine keywords for any data field with the results and search conditions preserved, and (3) easily browsing (a portion of) reference database. Although MacRefer cannot be recognized as an absolute alternative of EndNote Plus because of several limitations inherent to HyperCard, the compensatory use of these two programs will expand the personal utilization of bibliographic databases.

  15. Susceptibility of beige mice to Mycobacterium avium: role of neutrophils.

    PubMed Central

    Appelberg, R; Castro, A G; Gomes, S; Pedrosa, J; Silva, M T

    1995-01-01

    The beige mutation in C57BL/6 mice has been shown to increase the susceptibility to infection by Mycobacterium avium. In this study, we confirmed those results and showed that the effect of the beige mutation was most obvious after infection with a strain of lower virulence than with a highly virulent isolate of M. avium. The dissemination of M. avium from the gut was observed with both C57BL/6 and beige mice but was faster in the latter. The expression of gamma interferon (IFN-gamma) and the priming for tumor necrosis factor production during an in vivo infection were similar between beige and immunocompetent C57BL/6 mice. IFN-gamma produced during the infection of beige mice was protective in the spleen, and the administration of recombinant IFN-gamma restored the resistance in the spleen to levels similar to those found in control mice. There were no histological differences between wild-type and beige mice with respect to granuloma formation in the liver. The increased susceptibility of beige mice to M. avium as manifested in the liver was reduced by transfusing neutrophils from wild-type C57BL/6 mice. Likewise, depletion of neutrophils from C57BL/6 mice rendered them as susceptible to M. avium infection of the liver as beige mice. Our results point to the participation of neutrophils in the defect of beige mice in addition to other defects. Furthermore, these results show that neutrophils play a significant role in the defense mechanisms against mycobacterial infections and that beige animals may be a useful model for study of the role of neutrophils in mycobacteriosis. PMID:7642266

  16. Maize multiple archesporial cells 1 (mac1), an ortholog of rice TDL1A, modulates cell proliferation and identity in early anther development.

    PubMed

    Wang, Chung-Ju Rachel; Nan, Guo-Ling; Kelliher, Timothy; Timofejeva, Ljudmilla; Vernoud, Vanessa; Golubovskaya, Inna N; Harper, Lisa; Egger, Rachel; Walbot, Virginia; Cande, W Zacheus

    2012-07-01

    To ensure fertility, complex somatic and germinal cell proliferation and differentiation programs must be executed in flowers. Loss-of-function of the maize multiple archesporial cells 1 (mac1) gene increases the meiotically competent population and ablates specification of somatic wall layers in anthers. We report the cloning of mac1, which is the ortholog of rice TDL1A. Contrary to prior studies in rice and Arabidopsis in which mac1-like genes were inferred to act late to suppress trans-differentiation of somatic tapetal cells into meiocytes, we find that mac1 anthers contain excess archesporial (AR) cells that proliferate at least twofold more rapidly than normal prior to tapetal specification, suggesting that MAC1 regulates cell proliferation. mac1 transcript is abundant in immature anthers and roots. By immunolocalization, MAC1 protein accumulates preferentially in AR cells with a declining radial gradient that could result from diffusion. By transient expression in onion epidermis, we demonstrate experimentally that MAC1 is secreted, confirming that the predicted signal peptide domain in MAC1 leads to secretion. Insights from cytology and double-mutant studies with ameiotic1 and absence of first division1 mutants confirm that MAC1 does not affect meiotic cell fate; it also operates independently of an epidermal, Ocl4-dependent pathway that regulates proliferation of subepidermal cells. MAC1 both suppresses excess AR proliferation and is responsible for triggering periclinal division of subepidermal cells. We discuss how MAC1 can coordinate the temporal and spatial pattern of cell proliferation in maize anthers.

  17. MAC, material accounting database user guide

    SciTech Connect

    Russell, V.K.

    1994-09-22

    The K Basins Material Accounting (MAC) database system user guide describes the user features and functions, and the document is structured like the database menus. This document presents the MAC database system user instructions which explain how to record the movements and configuration of canisters and materials within the K Basins on the computer, the mechanics of handling encapsulation tracking, and administrative functions associated with the system. This document includes the user instructions, which also serve as the software requirements specification for the system implemented on the microcomputer. This includes suggested user keystrokes, examples of screens displayed by the system, and reports generated by the system. It shows how the system is organized, via menus and screens. It does not explain system design nor provide programmer instructions.

  18. Millisecond timing on PCs and Macs.

    PubMed

    MacInnes, W J; Taylor, T L

    2001-05-01

    A real-time, object-oriented solution for displaying stimuli on Windows 95/98, MacOS and Linux platforms is presented. The program, written in C++, utilizes a special-purpose window class (GLWindow), OpenGL, and 32-bit graphics acceleration; it avoids display timing uncertainty by substituting the new window class for the default window code for each system. We report the outcome of tests for real-time capability across PC and Mac platforms running a variety of operating systems. The test program, which can be used as a shell for programming real-time experiments and testing specific processors, is available at http://www.cs.dal.ca/~macinnwj. We propose to provide researchers with a sense of the usefulness of our program, highlight the ability of many multitasking environments to achieve real time, as well as caution users about systems that may not achieve real time, even under optimal conditions.

  19. Deformation, Failure, and Fatigue Life of SiC/Ti-15-3 Laminates Accurately Predicted by MAC/GMC

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Arnold, Steven M.

    2002-01-01

    NASA Glenn Research Center's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) (ref.1) has been extended to enable fully coupled macro-micro deformation, failure, and fatigue life predictions for advanced metal matrix, ceramic matrix, and polymer matrix composites. Because of the multiaxial nature of the code's underlying micromechanics model, GMC--which allows the incorporation of complex local inelastic constitutive models--MAC/GMC finds its most important application in metal matrix composites, like the SiC/Ti-15-3 composite examined here. Furthermore, since GMC predicts the microscale fields within each constituent of the composite material, submodels for local effects such as fiber breakage, interfacial debonding, and matrix fatigue damage can and have been built into MAC/GMC. The present application of MAC/GMC highlights the combination of these features, which has enabled the accurate modeling of the deformation, failure, and life of titanium matrix composites.

  20. Insertion and deletion events that define the pathogen Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Alexander, David C; Turenne, Christine Y; Behr, Marcel A

    2009-02-01

    Mycobacterium avium comprises genetically related yet phenotypically distinct subspecies. Consistent with their common origin, whole-genome sequence comparisons have revealed extensive synteny among M. avium organisms. However, the sequenced strains also display numerous regions of heterogeneity that likely contribute to the diversity of the individual subspecies. Starting from a phylogenetic framework derived by multilocus sequence analysis, we examined the distribution of 25 large sequence polymorphisms across a panel of genetically defined M. avium strains. This distribution was most variable among M. avium subsp. hominissuis isolates. In contrast, M. avium subsp. paratuberculosis strains exhibited a characteristic profile, with all isolates containing a set of genomic insertions absent from other M. avium strains. The emergence of the pathogen from its putative M. avium subsp. hominissuis ancestor entailed the acquisition of approximately 125 kb of novel genetic material, followed by a second phase, characterized by reductive genomics. One genomic deletion is common to all isolates while additional deletions distinguish two major lineages of M. avium subsp. paratuberculosis. For the average strain, these losses total at least 38 kb (sheep lineage) to 90 kb (cattle lineage). This biphasic pattern of evolution, characterized by chromosomal gene acquisition with subsequent gene loss, describes the emergence of M. avium subsp. paratuberculosis and may serve as a general model for the origin of pathogenic mycobacteria.

  1. Host and bacterial factors control the Mycobacterium avium-induced chronic peritoneal granulocytosis in mice.

    PubMed Central

    Appelberg, R; Pedrosa, J M; Silva, M T

    1991-01-01

    Persistent peritoneal granulocytosis and elevated macrophage counts have been found in nine mouse strains from 8 to 90 days after infection with Mycobacterium avium. Peritoneal granulocytosis was higher in M. avium-resistant BALB/c. Bcgr (C.D2) mice, compared with congenic M. avium-susceptible BALB/c (Bcgs) animals. Although maximal granulocytosis values were not related to virulence of the inocula, the kinetics of the granulocytic response varied with the virulence of M. avium. Following infections by avirulent (rough) strains of M. avium, the peritoneal granulocytosis progressively declined in BALB/c and C3H/He mice. A similar decline in granulocyte number was observed in resistant C3H/He mice infected with virulent M. avium (smooth transparent strain). In both instances the decline in the peritoneal granulocytosis was associated with a progressive elimination of the inoculum. In the susceptible BALB/c mice, virulent M. avium strains induced progressive infection accompanied with a rapid decline in granulocyte number, whereas the infection with attenuated M. avium, which caused a chronic infection, induced persistent granulocytosis. The ability to recruit granulocytes following the intraperitoneal inoculation of a phlogistic substance (casein hydrolysate) was decreased in infected susceptible but not in infected resistant mice at 90 days of infection with virulent M. avium. PMID:1993357

  2. Thermal Inactivation of Mycobacterium avium subsp. paratuberculosis in Artificially Contaminated Milk by Direct Steam Injection.

    PubMed

    Peterz, Mats; Butot, Sophie; Jagadeesan, Balamurugan; Bakker, Douwe; Donaghy, John

    2016-05-01

    The efficiency of direct steam injection (DSI) at 105 °C for 3 s to inactivate Mycobacterium avium subsp. paratuberculosis in milk at a pilot-plant scale was investigated. Milk samples were artificially contaminated with M. avium subsp. paratuberculosis and also with cow fecal material naturally infected with M. avium subsp. paratuberculosis. We also tested milk artificially contaminated with Mycobacterium smegmatis as a candidate surrogate to compare thermal inactivation between M. smegmatis and M. avium subsp. paratuberculosis. Following the DSI process, no viable M. avium subsp. paratuberculosis or M. smegmatis was recovered using culture methods for both strains. For pure M. avium subsp. paratuberculosis cultures, a minimum reduction of 5.6 log10 was achieved with DSI, and a minimum reduction of 5.7 log10 was found with M. smegmatis. The minimum log10 reduction for wild-type M. avium subsp. paratuberculosis naturally present in feces was 3.3. In addition, 44 dairy and nondairy powdered infant formula (PIF) ingredients used during the manufacturing process of PIF were tested for an alternate source for M. avium subsp. paratuberculosis and were found to be negative by quantitative PCR (qPCR). In conclusion, the results obtained from this study indicate that a >7-fold-log10 reduction of M. avium subsp. paratuberculosis in milk can be achieved with the applied DSI process. M. avium subsp. paratuberculosis is widespread in dairy herds in many countries. M. avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle, and infected animals can directly or indirectly (i.e., fecal contamination) contaminate milk. Despite much research and debate, there is no conclusive evidence that M. avium subsp. paratuberculosis is a zoonotic bacterium, i.e., one that causes disease in humans. The presence of M. avium subsp. paratuberculosis or its DNA has been reported in dairy products, including pasteurized milk, cheese, and infant formula. In light of this

  3. Comparative genomic analysis of Mycobacterium avium subspecies obtained from multiple host species

    PubMed Central

    Paustian, Michael L; Zhu, Xiaochun; Sreevatsan, Srinand; Robbe-Austerman, Suelee; Kapur, Vivek; Bannantine, John P

    2008-01-01

    Background Mycobacterium avium (M. avium) subspecies vary widely in both pathogenicity and host specificity, but the genetic features contributing to this diversity remain unclear. Results A comparative genomic approach was used to identify large sequence polymorphisms among M. avium subspecies obtained from a variety of host animals. DNA microarrays were used as a platform for comparing mycobacterial isolates with the sequenced bovine isolate M. avium subsp. paratuberculosis (MAP) K-10. Open reading frames (ORFs) were classified as present or divergent based on the relative fluorescent intensities of the experimental samples compared to MAP K-10 DNA. Multiple large polymorphic regions were found in the genomes of MAP isolates obtained from sheep. One of these clusters encodes glycopeptidolipid biosynthesis enzymes which have not previously been identified in MAP. M. avium subsp. silvaticum isolates were observed to have a hybridization profile very similar to yet distinguishable from M. avium subsp. avium. Isolates obtained from cattle (n = 5), birds (n = 4), goats (n = 3), bison (n = 3), and humans (n = 9) were indistinguishable from cattle isolate MAP K-10. Conclusion Genome diversity in M. avium subspecies appears to be mediated by large sequence polymorphisms that are commonly associated with mobile genetic elements. Subspecies and host adapted isolates of M. avium were distinguishable by the presence or absence of specific polymorphisms. PMID:18366709

  4. Clearance of bacteria in turkeys with Bordetella avium-induced tracheitis.

    PubMed

    Ficken, M D; Edwards, J F; Lay, J C

    1986-01-01

    Quantitative clearance of aerosolized Escherichia coli from the trachea, lung, and air sacs was measured in turkeys infected with Bordetella avium. Clearance of E. coli in turkeys with B. avium-induced tracheitis was minimally affected early in infection. Sixteen to 23 days after infection with B. avium, sporadic, mild depressions in clearance of E. coli were observed in the tracheas, which had large areas of deciliated tracheal epithelium or replacement of normal epithelium by immature hyperplastic epithelium or metaplastic squamous epithelium. Clearance of E. coli from the lung and air sacs was minimally affected in turkeys infected with B. avium.

  5. Thermal Inactivation of Mycobacterium avium subsp. paratuberculosis in Artificially Contaminated Milk by Direct Steam Injection

    PubMed Central

    Butot, Sophie; Jagadeesan, Balamurugan; Bakker, Douwe; Donaghy, John

    2016-01-01

    ABSTRACT The efficiency of direct steam injection (DSI) at 105°C for 3 s to inactivate Mycobacterium avium subsp. paratuberculosis in milk at a pilot-plant scale was investigated. Milk samples were artificially contaminated with M. avium subsp. paratuberculosis and also with cow fecal material naturally infected with M. avium subsp. paratuberculosis. We also tested milk artificially contaminated with Mycobacterium smegmatis as a candidate surrogate to compare thermal inactivation between M. smegmatis and M. avium subsp. paratuberculosis. Following the DSI process, no viable M. avium subsp. paratuberculosis or M. smegmatis was recovered using culture methods for both strains. For pure M. avium subsp. paratuberculosis cultures, a minimum reduction of 5.6 log10 was achieved with DSI, and a minimum reduction of 5.7 log10 was found with M. smegmatis. The minimum log10 reduction for wild-type M. avium subsp. paratuberculosis naturally present in feces was 3.3. In addition, 44 dairy and nondairy powdered infant formula (PIF) ingredients used during the manufacturing process of PIF were tested for an alternate source for M. avium subsp. paratuberculosis and were found to be negative by quantitative PCR (qPCR). In conclusion, the results obtained from this study indicate that a >7-fold-log10 reduction of M. avium subsp. paratuberculosis in milk can be achieved with the applied DSI process. IMPORTANCE M. avium subsp. paratuberculosis is widespread in dairy herds in many countries. M. avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle, and infected animals can directly or indirectly (i.e., fecal contamination) contaminate milk. Despite much research and debate, there is no conclusive evidence that M. avium subsp. paratuberculosis is a zoonotic bacterium, i.e., one that causes disease in humans. The presence of M. avium subsp. paratuberculosis or its DNA has been reported in dairy products, including pasteurized milk, cheese, and infant formula

  6. Visualization of integrin Mac-1 in vivo

    PubMed Central

    Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Topham, David J; Kim, Minsoo

    2015-01-01

    β2 integrins play critical roles in migration of immune cells and in the interaction with other cells, pathogens, and the extracellular matrix. Among the β2 integrins, Mac-1 (Macrophage antigen-1), composed of CD11b and CD18, is mainly expressed in innate immune cells and plays a major role in cell migration and trafficking. In order to image Mac-1-expressing cells both in live cells and mouse, we generated a knock-in (KI) mouse strain expressing CD11b conjugated with monomeric yellow fluorescent protein (mYFP). Expression of CD11b-mYFP protein was confirmed by Western blot and silver staining of CD11b-immunoprecipitates and total cell lysates from the mouse splenocytes. Mac-1-mediated functions of the KI neutrophils were comparable with those in WT cells. The fluorescence intensity of CD11b-mYFP was sufficient to image CD11b expressing cells in live mice using intravital two-photon microscopy. In vitro, dynamic changes in the intracellular localization of CD11b molecules could be measured by epifluorescent microscopy. Finally, CD11b-expressing immune cells from tissue were easily detected by flow cytometry without anti-CD11b antibody staining. PMID:26342259

  7. Paired lunar meteorites MAC88104 and MAC88105: A new FAN of lunar petrology

    SciTech Connect

    Neal, C.R. Univ. of Notre Dame, IN ); Taylor, L.A. ); Lui, Yungang; Schmitt, R.A. )

    1991-11-01

    New lunar meteorite MAC88104/5 represents an exciting new opportunity to study a potentially unsampled region of the Moon. The authors have analyzed six thin sections by electron microprobe and three bulk samples by Instrumental Neutron Activation (INA) in order to determine the chemical characteristics of this new lunar sample. Lunar meteorite MAC88104/5 is dominated by lithologies of the ferroan anorthosite (FAN) suite and contains abundant granulitized highland clasts, devitrified glass beads of impact origin, and two small clasts which appear to be of basaltic origin. One of these basaltic clasts (clast E in MAC88105,84) is probably mesostasis material, whereas the second larger clast (clast G) may be similar to the Very Low-Ti (VLT) or low-Ti/high-alumina mare basalts. Impact melt clasts MAC88105,69 and ,72 have major and trace element compositions similar to the bulk meteorite. There is little evidence of any LKFM (Low-K Fra Mauro or low-K KREEP) contribution to this meteorite, as MAC88104/5 and other brecciated lunar meteorites are Fe-rich and poor in the incompatible elements relative to Apollo 16 regolith and feldspathic breccias. While the exact site of origin for the lunar meteorites cannot be pinpointed, it is evident that they were divided from a relatively KREEP-free ferroan anorthosite terrain.

  8. Lactoferricin Peptides Increase Macrophages' Capacity To Kill Mycobacterium avium

    PubMed Central

    Silva, Tânia; Moreira, Ana C.; Nazmi, Kamran; Moniz, Tânia; Vale, Nuno; Rangel, Maria; Gomes, Paula; Bolscher, Jan G. M.; Rodrigues, Pedro N.; Bastos, Margarida

    2017-01-01

    ABSTRACT Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17–30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture. In the present work, those peptides were tested against M. avium living inside its natural host cell, the macrophage. We found that the peptides increased the antimicrobial action of the conventional antibiotic ethambutol inside macrophages. Moreover, the d-enantiomer of the lactoferricin peptide (d-LFcin17–30) was more stable and induced significant killing of intracellular mycobacteria by itself. Interestingly, d-LFcin17–30 did not localize to M. avium-harboring phagosomes but induced the production of proinflammatory cytokines and increased the formation of lysosomes and autophagosome-like vesicles. These results lead us to conclude that d-LFcin17–30 primes macrophages for intracellular microbial digestion through phagosomal maturation and/or autophagy, culminating in mycobacterial killing. IMPORTANCE The genus Mycobacterium comprises several pathogenic species, including M. tuberculosis, M. leprae, M. avium, etc. Infections caused by these bacteria are particularly difficult to treat due to their intrinsic impermeability, low growth rate, and intracellular localization. Antimicrobial peptides are increasingly acknowledged as potential treatment tools, as they have a high spectrum of activity, low tendency to induce bacterial resistance, and immunomodulatory properties. In

  9. A Mycobacterium avium subsp. paratuberculosis Predicted Serine Protease Is Associated with Acid Stress and Intraphagosomal Survival

    PubMed Central

    Kugadas, Abirami; Lamont, Elise A.; Bannantine, John P.; Shoyama, Fernanda M.; Brenner, Evan; Janagama, Harish K.; Sreevatsan, Srinand

    2016-01-01

    The ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although, studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophages and MAC-T cells that coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increased bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5) conditions, compared to the parent strain. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted. PMID:27597934

  10. W-MAC: A Workload-Aware MAC Protocol for Heterogeneous Convergecast in Wireless Sensor Networks

    PubMed Central

    Xia, Ming; Dong, Yabo; Lu, Dongming

    2011-01-01

    The power consumption and latency of existing MAC protocols for wireless sensor networks (WSNs) are high in heterogeneous convergecast, where each sensor node generates different amounts of data in one convergecast operation. To solve this problem, we present W-MAC, a workload-aware MAC protocol for heterogeneous convergecast in WSNs. A subtree-based iterative cascading scheduling mechanism and a workload-aware time slice allocation mechanism are proposed to minimize the power consumption of nodes, while offering a low data latency. In addition, an efficient schedule adjustment mechanism is provided for adapting to data traffic variation and network topology change. Analytical and simulation results show that the proposed protocol provides a significant energy saving and latency reduction in heterogeneous convergecast, and can effectively support data aggregation to further improve the performance. PMID:22163753

  11. Host responses to persistent Mycobacterium avium subspecies paratuberculosis infection in surgically isolated bovine ileal segments.

    PubMed

    Charavaryamath, Chandrashekhar; Gonzalez-Cano, Patricia; Fries, Patrick; Gomis, Susantha; Doig, Kimberley; Scruten, Erin; Potter, Andrew; Napper, Scott; Griebel, Philip J

    2013-02-01

    A lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections with Mycobacterium avium subsp. paratuberculosis. A model was developed for the controlled delivery of a defined dose of M. avium subsp. paratuberculosis to surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistent M. avium subsp. paratuberculosis infections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment. M. avium subsp. paratuberculosis remained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node. M. avium subsp. paratuberculosis-specific T cell proliferative responses included both CD4 and γδ T cell receptor (γδTcR) T cell responses in the draining mesenteric lymph node. The levels of CD8(+) and γδTcR(+) T cells increased significantly (P < 0.05) in the lamina propria, and M. avium subsp. paratuberculosis-specific tumor necrosis factor alpha (TNF-α) and gamma interferon secretion by lamina propria leukocytes was also significantly (P < 0.05) increased. There was a significant (P < 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed by M. avium subsp. paratuberculosis infection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized enteric M. avium subsp. paratuberculosis infection in cattle and facilitated the analysis of M. avium subsp. paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses to M. avium subsp. paratuberculosis infection and

  12. Intramacrophage growth of Mycobacterium avium during infection of mice.

    PubMed Central

    Frehel, C; de Chastellier, C; Offredo, C; Berche, P

    1991-01-01

    Growth of the virulent Mycobacterium avium strain TMC 724 in host tissues during persistent infection of mice was studied. Following intravenous infection of C57BL/6 mice, the kinetics of bacterial growth was biphasic in the spleen and liver, with a significant reduction of the multiplication rate after day 21 to 28 of infection. An electron-microscopic study of the liver and spleen of infected mice showed that the bacteria were strictly intracellular. They were observed within inflammatory macrophages populating granulomas disseminated in host tissues. The bacteria were confined to the phagosome compartment, and they were encapsulated. Phagosome-lysosome fusions were encountered, but the bacteria showed no visible signs of degradation and continued to multiply. These results are the first in vivo evidence that virulent M. avium multiplies exclusively intracellularly and that encapsulated bacteria resist the microbicidal mechanisms of macrophages inside the phagosomal compartment. Images PMID:2037382

  13. Serologic tests for detecting antibodies against Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis in Eurasian wild boar (Sus scrofa scrofa).

    PubMed

    Boadella, Mariana; Lyashchenko, Konstantin; Greenwald, Reena; Esfandiari, Javan; Jaroso, Raquel; Carta, Tania; Garrido, Joseba M; Vicente, Joaquín; de la Fuente, José; Gortázar, Christian

    2011-01-01

    New tools to detect exposure of free-range Eurasian wild boar (Sus scrofa scrofa) to pathogenic mycobacteria would be valuable for improved disease surveillance and wildlife management. Two hundred sera from wild boar of known Mycobacterium bovis infection status were used to evaluate test suitability for the detection of antibodies against M. bovis and Mycobacterium avium subsp. paratuberculosis (or cross-reacting members of the M. avium complex). Two traditional enzyme-linked immunosorbent assays were evaluated using M. bovis purified protein derivative (bPPD) and paratuberculosis protoplasmatic antigen 3 (PPA3) as antigens, respectively, and a new point-of-care test format for bovine tuberculosis (bTB) that uses the innovative dual-path platform (DPP TB) test. The effect of individual factors (sex, age, lesions) on the diagnostic performance of the serologic tests was also determined. Although the DPP had a sensitivity of 89.6% and a specificity of 90.4%, for bPPD, the sensitivity was 79.2% and the specificity 100%. Both tests had a kappa agreement of 0.80. Sixty-five of 68 (95.6%) wild boar sera with antibodies against the PPA3 antigen corresponded to known M. bovis-infected wild boar. Significant differences were not observed in the bPPD and DPP readings among lesion categories or between age classes. A slight sex-related difference in sensitivity toward males in the DPP was found, but it was not detected in the bPPD enzyme-linked immunosorbent assay. The results support the use of antibody-based diagnostic tests for both large-scale and individual bTB testing of Eurasian wild boar and suggest that wild boar cannot be used as sentinels for infections caused by M. avium complex members.

  14. Mycobacterium avium-intracellulare: a rare cause of subacromial bursitis.

    PubMed

    Sinha, Raj; Tuckett, John; Hide, Geoff; Dildey, Petra; Karsandas, Alvin

    2015-01-01

    Septic subacromial bursitis is an uncommon disorder with only a few reported cases in the literature. The most common causative organism is Staphylococcus aureus. We report the case of a 61-year-old female with a septic subacromial bursitis where the causative organism was found to be Mycobacterium avium-intracellulare (MAI). The diagnosis was only made following a biopsy, and we use this case to highlight the importance of recognising the need to consider a biopsy and aspiration in atypical situations.

  15. Molecular identification of Mycobacterium avium subsp. silvaticum by duplex high-resolution melt analysis and subspecies-specific real-time PCR.

    PubMed

    Rónai, Zsuzsanna; Csivincsik, Ágnes; Dán, Ádám

    2015-05-01

    Accurate identification of mycobacterial species and subspecies is essential to evaluate their significance and to perform epidemiological studies. The subspecies of Mycobacterium avium have different attributes but coincide in their zoonotic potential. Our knowledge about M. avium subsp. silvaticum is limited, since its identification is uncertain. Mycobacterium avium subsp. avium and M. avium subsp. silvaticum can be discriminated from each other based only on phenotypic characteristics, as they have almost identical genome sequences. Here we describe the development of a diagnostic method which enables the molecular identification of M. avium subsp. silvaticum and discrimination from M. avium subsp. avium based on genomic differences in a duplex high-resolution melt and M. avium subsp. silvaticum-specific mismatch real-time PCR. The developed assay was tested on reference strains and 199 field isolates, which were analyzed by phenotypic methods previously. This assay not only identified all 63 M. avium subsp. silvaticum and 138 M. avium subsp. avium strains correctly but also enabled the detection of mixed M. avium subsp. avium-M. avium subsp. silvaticum cultures. This is the first time that such a large panel of strains has been analyzed, and we also report the first isolation of M. avium subsp. silvaticum from red fox, red deer, wild boar, cattle, and badger. This assay is reliable, rapid, simple, inexpensive, and robust. It eliminates the long-existing problem of ambiguous phenotypic identification and opens up the possibility for detailed and comprehensive strain studies.

  16. Molecular Identification of Mycobacterium avium subsp. silvaticum by Duplex High-Resolution Melt Analysis and Subspecies-Specific Real-Time PCR

    PubMed Central

    Csivincsik, Ágnes; Dán, Ádám

    2015-01-01

    Accurate identification of mycobacterial species and subspecies is essential to evaluate their significance and to perform epidemiological studies. The subspecies of Mycobacterium avium have different attributes but coincide in their zoonotic potential. Our knowledge about M. avium subsp. silvaticum is limited, since its identification is uncertain. Mycobacterium avium subsp. avium and M. avium subsp. silvaticum can be discriminated from each other based only on phenotypic characteristics, as they have almost identical genome sequences. Here we describe the development of a diagnostic method which enables the molecular identification of M. avium subsp. silvaticum and discrimination from M. avium subsp. avium based on genomic differences in a duplex high-resolution melt and M. avium subsp. silvaticum-specific mismatch real-time PCR. The developed assay was tested on reference strains and 199 field isolates, which were analyzed by phenotypic methods previously. This assay not only identified all 63 M. avium subsp. silvaticum and 138 M. avium subsp. avium strains correctly but also enabled the detection of mixed M. avium subsp. avium-M. avium subsp. silvaticum cultures. This is the first time that such a large panel of strains has been analyzed, and we also report the first isolation of M. avium subsp. silvaticum from red fox, red deer, wild boar, cattle, and badger. This assay is reliable, rapid, simple, inexpensive, and robust. It eliminates the long-existing problem of ambiguous phenotypic identification and opens up the possibility for detailed and comprehensive strain studies. PMID:25740770

  17. Effect of Prunus avium roots on river bank strong.

    PubMed

    Bibalani, Ghassem Habibi; Bazhrang, Zia; Mohsenifar, Hani; Shibaei, Naeime; Joodi, Lila

    2008-04-15

    A pulling effect by side roots is one way in which roots help to side in-plane strong of a little depth soil mass. In contrast to the effect of vertically-enlarge roots, whereby soil is strengthened by an increase in its shear strength, the pulling effect strengthens the soil by increasing the tensile strength of the rooted soil zone. To verify whether or not a pulling effect exists in the root system of Prunus avium in the Roudsar, North Iran and to study the importance and size of this effect, a direct in situ test was led at a site in the Chaboksar Forests. The results from the site showed that, in the surface soil (0-30 cm), Side roots can provide a pull force of up to 490-712 N (Newtons) over a vertical cross-section area of 20-50 cm2, or an enhance in the pulling stability of the rooted soil by about 48.1%. The test results suggest that, together with the Prunus avium vertical roots, which keep the little depth rooted soil zone to the deep and more stable soil mass, the side roots of the Prunus avium, with their pulling effect, are able to make less against little depth instability in the forest slopes, such as little depth slide, to a certain degree.

  18. Complete genome sequence of Mycobacterium avium subsp. paratuberculosis, isolated from human breast milk

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subsp paratuberculosis is the etiologic agent of Johne’s disease. We report the draft genome sequences of six M. avium subsp paratuberculosis isolates obtained from diverse hosts including bison, cattle and sheep. These sequences will deepen our understanding of host association ...

  19. Profiling Host Antibody Responses to Mycobacterium avium subspecies paratuberculosis Infection Using Protein Arrays

    USDA-ARS?s Scientific Manuscript database

    Along with the complete genome sequence of Mycobacterium avium subspecies paratuberculosis, technologies are now developed for the construction of protein arrays to detect the presence of antibodies against M. avium subsp paratuberculosis in host serum. The power of this approach is that it enable...

  20. Draft Genome Sequence of Bordetella avium Nh1210, an Outbreak Strain of Lockjaw Syndrome.

    PubMed

    Moreno, Luisa Z; Knöbl, Terezinha; Grespan, André A; Felizardo, Maria R; Gomes, Cleise R; Ferreira, Thais S P; Xavier de Oliveira, Maria Gabriela; Myriantheus, Livia; Moreno, Andrea Micke

    2015-03-12

    Bordetella avium is a highly contagious bacterium that infects the upper respiratory tract of birds. B. avium Nh1210 is an outbreak strain of lockjaw syndrome in juvenile cockatiel chicks (Nymphicus hollandicus). Here, we report the draft genome sequence of strain Nh1210. Copyright © 2015 Moreno et al.

  1. Draft Genome Sequence of Bordetella avium Nh1210, an Outbreak Strain of Lockjaw Syndrome

    PubMed Central

    Moreno, Luisa Z.; Knöbl, Terezinha; Grespan, André A.; Felizardo, Maria R.; Gomes, Cleise R.; Ferreira, Thais S. P.; Xavier de Oliveira, Maria Gabriela; Myriantheus, Livia

    2015-01-01

    Bordetella avium is a highly contagious bacterium that infects the upper respiratory tract of birds. B. avium Nh1210 is an outbreak strain of lockjaw syndrome in juvenile cockatiel chicks (Nymphicus hollandicus). Here, we report the draft genome sequence of strain Nh1210. PMID:25767244

  2. Roles for Cell Wall Glycopeptidolipid in Surface Adherence and Planktonic Dispersal of Mycobacterium avium

    EPA Science Inventory

    The opportunistic pathogen Mycobacterium avium is a significant inhabitant of biofilms in drinking water distribution systems. M. avium expresses on its cell surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the core GPL in biofilm formation by M. aviu...

  3. Roles for Cell Wall Glycopeptidolipid in Surface Adherence and Planktonic Dispersal of Mycobacterium avium

    EPA Science Inventory

    The opportunistic pathogen Mycobacterium avium is a significant inhabitant of biofilms in drinking water distribution systems. M. avium expresses on its cell surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the core GPL in biofilm formation by M. aviu...

  4. Presence of Mycobacterium avium subsp. paratuberculosis in Environmental Samples Collected on Commercial Dutch Dairy Farms ▿

    PubMed Central

    Eisenberg, Susanne W. F.; Koets, Ad P.; Hoeboer, Jeroen; Bouman, Marina; Heederik, Dick; Nielen, Mirjam

    2010-01-01

    Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease in cattle, was identified in settled-dust samples of Dutch commercial dairy farms, both in the dairy barn and in the young stock housing. Bioaerosols may play a role in within-farm M. avium subsp. paratuberculosis transmission. PMID:20656861

  5. Use of restriction fragment length polymorphism as a genetic marker for typing Mycobacterium avium strains.

    PubMed

    Roiz, M P; Palenque, E; Guerrero, C; Garcia, M J

    1995-05-01

    Restriction fragment length polymorphism (RFLP) was used to study 75 clinical isolates identified as Mycobacterium avium. Two repetitive insertion sequences, IS1311 and IS900, were used as DNA probes. Although less than 25% of isolates showed RFLP patterns with IS900, all strains gave banding patterns with IS1311. M. avium strains isolated from patients with AIDS exhibited marked polymorphism with both probes.

  6. Cell wall peptidolipids of Mycobacterium avium: from genetic prediction to exact structure of a nonribosomal peptide

    USDA-ARS?s Scientific Manuscript database

    Total lipids from an M. avium subsp. paratuberculosis (Map) ovine strain (S-type) contained no identifiable glycopeptidolipids or lipopentapeptide, yet both lipids are present in other M. avium subspecies. We determined the genetic and phenotypic basis for this difference using sequence analysis and...

  7. MacArthur Foundation Prize Fellows

    NASA Astrophysics Data System (ADS)

    Four of the 19 persons selected as prize fellows by the John D. and Catherine MacArthur Foundation specialize in the earth, ocean, or space sciences. The four are John P. Holdren, Robert W. Kates, Paul G. Richards, and Joseph H. Taylor.The awards, ranging from $24,000 to $60,000 annually for 5 years, are unrestricted; the recipients may pursue any field of endeavor and are not required to publish a paper or to meet similar requirements. The exact amount of the award is dependent on the recipient's age; older prize fellows receive larger awards than do younger ones.

  8. Introduction to MacDraft. High-Technology Training Module.

    ERIC Educational Resources Information Center

    Traxler, Gene

    This training module on MacDraft is part of a computer drafting skills unit on communications technology for grades 9-12. The objective is for each student to complete a drawing on the MacIntosh computer using the MacDraft software program. This drawing is to be dimensioned with a dual system and is to include a border and title block. This module…

  9. Wireless Sensor Networks Energy-Efficient MAC Protocol

    NASA Astrophysics Data System (ADS)

    Lijuan, Du; Yuanpeng, Wang; WeiPeng, Jing

    This paper presents a new wireless sensor network energy-efficient MAC protocol, ES-MAC protocol, and shows the results of simulation experiments. During the transmission the nodes do not send ACK packages while use a small amount of new information packets, so they can reduce unnecessary energy loss and wasted time. The theoretical analysis and simulation results show that ES-MAC protocol reduces energy consumption while reducing network latency and improving network throughput.

  10. APC-MAC/TA: Adaptive Power Controlled MAC Protocol with Traffic Awareness for Wireless Sensor Networks

    NASA Astrophysics Data System (ADS)

    Woo, Seok; Kim, Kiseon

    In this paper, we propose an adaptive power controlled MAC protocol with a traffic-aware scheme specifically designed to reduce both energy and latency in wireless sensor networks. Typically, existing MAC protocols for sensor networks sacrifice latency performance for node energy efficiency. However, some sensor applications for emergencies require rather fast transmissions of sensed data, where we need to consider both energy and latency together. The proposed MAC protocol includes two novel ideas: one is a transmission power control scheme for improving latency in high traffic loads, and the other is a traffic-aware scheme to save more energy in low traffic loads. The transmission power control scheme increases channel utilization by mitigating interference between nodes, and the traffic-aware scheme allows nodes to sleep to reduce idle energy consumption when there are no traffic loads in a network. Simulation results show that the proposed protocol significantly reduces the latency as well as the energy consumption compared to the S-MAC protocol specifically for a large transmission power of nodes and low network traffic.

  11. Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease

    PubMed Central

    Deshpande, Devyani; Pasipanodya, Jotam G.

    2016-01-01

    Mycobacterium avium complex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonary M. avium disease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. PMID:26810646

  12. David MacKay's wooden blocks

    NASA Astrophysics Data System (ADS)

    Skilling, John

    2017-06-01

    This paper is dedicated to the memory of Professor Sir David MacKay FRS. In his inspiring last talk, MacKay discussed the problem of packing his young son's identical wooden blocks, of size 2×1×1. How many ways are there of packing n3/2 such blocks into a cubical box of volume n3? This is the same problem as finding the entropy of cubic packing of dimeric molecules, so the investigation is not merely childish. Here, I use this example as an exemplar of the use of nested sampling in computational inference. In this analogy, the posterior covers the "glassy" arrangements of non-overlapping blocks in the box, whereas the prior represents the wider set of unrestricted model configurations. The required number of possible glass states is the compressive prior-to-posterior fraction of the known number of model configurations. And the compression (as logarithm) is immediately available from the number of equilibrating iterations in nested sampling. The clarity of this example offers useful lessons for computational inference more generally.

  13. MacCready awarded Outstanding Student Paper

    NASA Astrophysics Data System (ADS)

    Parker MacCready was selected by the Ocean Sciences Section to receive their Outstanding Student Paper Award from the 1989 Fall Meeting in San Francisco for his paper entitled “Stratified Spin-up Over a Slope.” Following receipt of his Bachelor's degree in architecture from Yale in 1982, MacCready went to China for 5 months to study the language. On his return to Pasadena he worked for 3 years for Aerovironment, Inc., concentrating on building and flying a human-powered aircraft and a giant wing-flapping replica of a pterosaur. Having become interested in the aerodynamics of flappingwing propulsion, he continued his studies at Caltech, where he received his Master's degree in 1986. His informal thesis project was a human-powered hydrofoil boat with flapping-wing propulsion. He is currently working on his doctorate in physical oceanography at the University of Washington, where he is studying the dynamics of stratified, rotating boundary layers over topography. His switch to oceanography was motivated by his feeling that environmental fluid mechanics would become an increasingly relevant subject in light of increasing world pollution. In the future he hopes to go into environmental politics, perhaps in a scientific advisory role.

  14. Assessing the Inactivation of Mycobacterium avium subsp. paratuberculosis during Composting of Livestock Carcasses

    PubMed Central

    Tkachuk, Victoria L.; Krause, Denis O.; McAllister, Tim A.; Buckley, Katherine E.; Reuter, Tim; Hendrick, Steve

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in ruminants, with substantial economic impacts on the cattle industry. Johne's disease is known for its long latency period, and difficulties in diagnosis are due to insensitivities of current detection methods. Eradication is challenging as M. avium subsp. paratuberculosis can survive for extended periods within the environment, resulting in new infections in naïve animals (W. Xu et al., J. Environ. Qual. 38:437-450, 2009). This study explored the use of a biosecure, static composting structure to inactivate M. avium subsp. paratuberculosis. Mycobacterium smegmatis was also assessed as a surrogate for M. avium subsp. paratuberculosis. Two structures were constructed to hold three cattle carcasses each. Naturally infected tissues and ground beef inoculated with laboratory-cultured M. avium subsp. paratuberculosis and M. smegmatis were placed in nylon and plastic bags to determine effects of temperature and compost environment on viability over 250 days. After removal, samples were cultured and growth of both organisms was assessed after 12 weeks. After 250 days, M. avium subsp. paratuberculosis was still detectable by PCR, while M. smegmatis was not detected after 67 days of composting. Furthermore, M. avium subsp. paratuberculosis remained viable in both implanted nylon and plastic bags over the composting period. As the compost never reached a homogenous thermophilic (55 to 65°C) state throughout each structure, an in vitro experiment was conducted to examine viability of M. avium subsp. paratuberculosis after exposure to 80°C for 90 days. Naturally infected lymph tissues were mixed with and without compost. After 90 days, M. avium subsp. paratuberculosis remained viable despite exposure to temperatures typically higher than that achieved in compost. In conclusion, it is unlikely composting can be used as a means of inactivating M. avium subsp. paratuberculosis associated with cattle

  15. TreeMAC: Localized TDMA MAC protocol for real-time high-data-rate sensor networks

    USGS Publications Warehouse

    Song, W.-Z.; Huang, R.; Shirazi, B.; LaHusen, R.

    2009-01-01

    Earlier sensor network MAC protocols focus on energy conservation in low-duty cycle applications, while some recent applications involve real-time high-data-rate signals. This motivates us to design an innovative localized TDMA MAC protocol to achieve high throughput and low congestion in data collection sensor networks, besides energy conservation. TreeMAC divides a time cycle into frames and each frame into slots. A parent node determines the children's frame assignment based on their relative bandwidth demand, and each node calculates its own slot assignment based on its hop-count to the sink. This innovative 2-dimensional frame-slot assignment algorithm has the following nice theory properties. First, given any node, at any time slot, there is at most one active sender in its neighborhood (including itself). Second, the packet scheduling with TreeMAC is bufferless, which therefore minimizes the probability of network congestion. Third, the data throughput to the gateway is at least 1/3 of the optimum assuming reliable links. Our experiments on a 24-node testbed show that TreeMAC protocol significantly improves network throughput, fairness, and energy efficiency compared to TinyOS's default CSMA MAC protocol and a recent TDMA MAC protocol Funneling-MAC. Partial results of this paper were published in Song, Huang, Shirazi and Lahusen [W.-Z. Song, R. Huang, B. Shirazi, and R. Lahusen, TreeMAC: Localized TDMA MAC protocol for high-throughput and fairness in sensor networks, in: The 7th Annual IEEE International Conference on Pervasive Computing and Communications, PerCom, March 2009]. Our new contributions include analyses of the performance of TreeMAC from various aspects. We also present more implementation detail and evaluate TreeMAC from other aspects. ?? 2009 Elsevier B.V.

  16. The fibroblast growth factor-2 arrests Mycobacterium avium sp. paratuberculosis growth and immunomodulates host response in macrophages.

    PubMed

    Wang, Jianjun; Wang, Zeyou; Yao, Yongliang; Wu, Jianhong; Tang, Xin; Gu, Tao; Li, Guangxin

    2015-07-01

    Mycobacterium tuberculosisis (M. tb) epidemic is one of the most severe health problem worldwide, while mechanisms underlying its pathogenesis and host immune responses remain unclear. Mycobacterium avium (M. avium), a mycobacterial species related to M. tb, shares similarities with M. tb in many ways. In this study, using M. avium infection of macrophages as a model, we systematically studied the effect of fibroblast growth factor-2 (FGF-2) on M. avium infection of macrophages. Our results showed that M. avium infection could increase FGF-2 expression on both mRNA and protein levels. M. avium infection elevated TNF-α and IFN-γ production while the addition of FGF-2 could further increase TNF-α but not IFN-γ level. M. avium infection could increase the expression of oxygen/nitrogen metabolism proteins iNOS and SOD-1, and FGF-2 had additive effect on the expression of these two proteins. M. avium infection had inhibitive effect on actin expression while FGF-2 could partly counteract such inhibition. Moreover, FGF-2 could inhibit M. avium proliferation in macrophages. Our results together indicate that macrophage-secreted FGF-2 upon M. avium infection could suppress M. avium proliferation through various ways including cytokine production, enhancement of phagocytosis as well as oxygen/nitrogen metabolism.

  17. 42 CFR 423.2122 - What evidence may be submitted to the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false What evidence may be submitted to the MAC. 423.2122..., MAC review, and Judicial Review § 423.2122 What evidence may be submitted to the MAC. (a) Appeal before the MAC on request for review of ALJ's decision. (1) If the MAC is reviewing an ALJ's decision...

  18. 42 CFR 405.1122 - What evidence may be submitted to the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false What evidence may be submitted to the MAC. 405.1122... Council Review § 405.1122 What evidence may be submitted to the MAC. (a) Appeal before the MAC on request for review of ALJ's decision. (1) If the MAC is reviewing an ALJ's decision, the MAC limits its review...

  19. Pathogenicity of Mycobacterium avium for human monocytes: absence of macrophage-activating factor activity of gamma interferon.

    PubMed Central

    Toba, H; Crawford, J T; Ellner, J J

    1989-01-01

    Mycobacterium avium is a frequent opportunistic pathogen in the acquired immunodeficiency syndrome (AIDS). We compared 12 strains of M. avium in an in vitro model of pathogenicity. Peripheral blood-derived monocytes from healthy individuals were infected with M. avium in vitro. Bacterial uptake and intracellular replication were assessed by microscopic count of acid-fast bacilli and CFU of bacteria, respectively, in lysed monocytes. The CFU assay showed that among five AIDS-associated strains, only one replicated in monocytes. Two of seven non-AIDS-associated strains replicated intracellularly. In addition, we examined the effect of gamma interferon (IFN-gamma) on M. avium infection. IFN-gamma treatment of monocytes decreased phagocytosis and had no effect on the intracellular replication of M. avium. Thus, most strains of M. avium do not multiply within monocytes from healthy individuals and IFN-gamma does not have macrophage-activating factor activity for M. avium infection of human monocytes. PMID:2491838

  20. SuperMacLang: Development of an Authoring System.

    ERIC Educational Resources Information Center

    Frommer, Judith; Foelsche, Otmar K. E.

    1999-01-01

    Describes the development of "SuperMacLang, the 1990s version of the MacLang authoring system. An analysis of various features of the program explains the ways in which certain aspects of collaboration and funding affected developer and programming decisions. (Author/VWL)

  1. Steven MacCall: Winner of LJ's 2010 Teaching Award

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    This article profiles Steven L. MacCall, winner of "Library Journal's" 2010 Teaching Award. An associate professor at the School of Library and Information Studies (SLIS) at the University of Alabama, Tuscaloosa, MacCall was nominated by Kathie Popadin, known as "Kpop" to the members of her cohort in the online MLIS program at SLIS. Sixteen of…

  2. Intel-Based Mac Computers Improve Teaching and Learning

    ERIC Educational Resources Information Center

    Technology & Learning, 2007

    2007-01-01

    Today, Mac computers offer schools an easy and powerful way to engage students in learning, foster 21st century skills and leverage existing software assets. Innovative software and hardware built into the Mac allows students to demonstrate their individual strengths--empowering them to be creators of content, rather than just consumers. Judging…

  3. Steven MacCall: Winner of LJ's 2010 Teaching Award

    ERIC Educational Resources Information Center

    Berry, John N., III

    2010-01-01

    This article profiles Steven L. MacCall, winner of "Library Journal's" 2010 Teaching Award. An associate professor at the School of Library and Information Studies (SLIS) at the University of Alabama, Tuscaloosa, MacCall was nominated by Kathie Popadin, known as "Kpop" to the members of her cohort in the online MLIS program at SLIS. Sixteen of…

  4. SuperMacLang: Development of an Authoring System.

    ERIC Educational Resources Information Center

    Frommer, Judith; Foelsche, Otmar K. E.

    1999-01-01

    Describes the development of "SuperMacLang, the 1990s version of the MacLang authoring system. An analysis of various features of the program explains the ways in which certain aspects of collaboration and funding affected developer and programming decisions. (Author/VWL)

  5. MAC of xenon and halothane in rhesus monkeys.

    PubMed

    Whitehurst, S L; Nemoto, E M; Yao, L; Yonas, H

    1994-10-01

    Local cerebral blood flow (LCBF) maps produced by 33% xenon-enhanced computed tomographic scanning (Xe/CT LCBF) are useful in the clinical diagnosis and management of patients with cerebrovascular disorders. However, observations in humans that 25-35% xenon (Xe) inhalation increases cerebral blood flow (CBF) have raised concerns that Xe/CT LCBF measurements may be inaccurate and that Xe inhalation may be hazardous in patients with decreased intracranial compliance. In contrast, 33% Xe does not increase CBF in rhesus monkeys. To determine whether this interspecies difference in the effect of Xe on CBF correlates with an interspecies difference in the anesthetic potency of Xe, we measured the minimum alveolar concentration (MAC) of Xe preventing movement to a tail-clamp stimulus in rhesus monkeys. Using a standard protocol for the determination of MAC in animals, we first measured the MAC of halothane (n = 5), and then used a combination of halothane and Xe to measure the MAC of Xe (n = 7). The halothane MAC was 0.99 +/- 0.12% (M +/- SD), and the Xe MAC was 98 +/- 15%. These results suggest that the MAC of Xe in rhesus monkeys is higher than the reported human Xe MAC value of 71%. Thus the absence of an effect of 33% Xe on CBF in the rhesus monkey may be related to its lower anesthetic potency.

  6. B-cell epitopes in the immunodominant p34 antigen of mycobacterium avium ssp. paratuberculosis recognized by antibodies from infected cattle.

    PubMed

    Ostrowski, M; Mundo, S L; Harris, N B; Barletta, R G; Lopez, O J

    2003-11-01

    Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis) causes Johne's disease, a chronic and fatal enteritis in ruminants. In the last stage of the disease, antibody titres rise and levels of interferon-gamma decrease, suggesting that the host-immune response is switching from a T helper 1 (Th1) to a Th2 profile. In infected cattle, the membrane protein p34 elicits the predominant humoral response against M. paratuberculosis. To map the B-cell epitopes of this antigen, affinity-purified bovine antibodies against the carboxy-terminal region of p34 were used to screen a 12-mer phage display library. Several phage clones carrying peptides resembling fragments of p34 were affinity selected. Based on the predicted amino acid sequence, peptides were chemically synthesized, which demonstrated reactivity with serum from naturally infected and p34-vaccinated cattle. Immunization of mice with these peptides elicited an anti-p34 antibody response. Two B-cell epitopes were identified and characterized. Based on the reactivity and the type of immune response elicited, epitope A was determined to be conformational, whereas epitope B was demonstrated to be sequential. Both epitopes were shown to be present in p34 proteins from M. avium ssp. avium or M. paratuberculosis but absent from M. intracellulare, the other member of the M. avium complex. Furthermore, both epitopes were mapped to regions of p34 that display high variability when compared to homologous proteins from other mycobacterial species of public and animal health importance. We hypothesize that these variable regions of p34 may play a role in the immunobiology of M. paratuberculosis infections.

  7. MacBurn's cylinder test problem

    SciTech Connect

    Shestakov, Aleksei I.

    2016-02-29

    This note describes test problem for MacBurn which illustrates its performance. The source is centered inside a cylinder with axial-extent-to-radius ratio s.t. each end receives 1/4 of the thermal energy. The source (fireball) is modeled as either a point or as disk of finite radius, as described by Marrs et al. For the latter, the disk is divided into 13 equal area segments, each approximated as a point source and models a partially occluded fireball. If the source is modeled as a single point, one obtains very nearly the expected deposition, e.g., 1/4 of the flux on each end and energy is conserved. If the source is modeled as a disk, both conservation and energy fraction degrade. However, errors decrease if the source radius to domain size ratio decreases. Modeling the source as a disk increases run-times.

  8. Paired lunar meteorites MAC88104 and MAC88105 - A new 'FAN' of lunar petrology. [ferroan anorthosite

    NASA Technical Reports Server (NTRS)

    Neal, Clive R.; Taylor, Lawrence A.; Lui, Yun-Gang; Schmitt, Roman A.

    1991-01-01

    To determine the chemical characteristics of the MAC88104/5 meteorite six thin sections and three bulk samples were analyzed by electron microprobe and instrumental neutron activation. It is concluded that this meteorite is dominated by lithologies of the ferroan anorthosite suite and contains abundant granulitized highland clasts, devitrified glass beads of impact origin, and two small clasts of basaltic origin. It is suggested that one of these basaltic clasts, clast E, is mesostasis material, and clast G is similar to the very low-Ti or low-Ti/high-alumina mare basalts. Impact melt clasts MAC88105, 69, and 72 have major and trace element compositions similar to the bulk meteorite.

  9. Middle Atmosphere Cooperation/Summer in Northern Europe (MAC/SINE) and MAC/Epsilon

    NASA Technical Reports Server (NTRS)

    Thrane, E. V.

    1989-01-01

    Two major international campaigns dedicated to the study of middle atmosphere dynamics in high latitudes were successfully completed in 1987. MAC/SINE (Middle Atmosphere Cooperation/Summer in Northern Europe) was carried out during the period 7 June to 19 July, whereas MAC/Epsilon took place in the period 12 October to 15 November. In both campaigns a large number of ground based and rocket techniques were used in a concerted effort to map the dynamical structure of the middle atmosphere over Northern Europe. Although the analysis of the observations has only just started, it is clear that a large and unique data set was obtained, which is believed will provide new insight into the dynamical processes in this interesting region of the atmosphere. A brief overview of the campaigns, their scientific aims, organization and structure is presented.

  10. The Arabidopsis MOS4-associated Complex Promotes MicroRNA Biogenesis and Precursor Messenger RNA Splicing.

    PubMed

    Jia, Tianran; Zhang, Bailong; You, Chenjiang; Zhang, Yong; Zeng, Liping; Li, Shengjun; Johnson, Kaeli C M; Yu, Bin; Li, Xin; Chen, Xuemei

    2017-09-25

    In Arabidopsis thaliana, the MOS4-ASSOCIATED COMPLEX (MAC) is required for defense and development. The evolutionarily conserved, putative RNA helicase MAC7 is a component of the Arabidopsis MAC and the human MAC7 homolog, Aquarius, is implicated in pre-mRNA splicing. Here, we show that mac7-1, a partial loss-of-function mutant in MAC7, and two other MAC subunit mutants, mac3a mac3b and prl1 prl2 (pleiotropic regulatory locus), exhibit reduced microRNA (miRNA) levels, indicating that MAC promotes miRNA biogenesis. The mac7-1 mutant shows reduced primary miRNA (pri-miRNA) levels without affecting miRNA gene (MIR) promoter activity or the half-life of pri-miRNA transcripts. As a nuclear protein, MAC7 is not concentrated in dicing bodies, but it affects the localization of HYPONASTIC LEAVES1 (HYL1), a key protein in pri-miRNA processing, to dicing bodies. Immunoprecipitation of HYL1 retrieved eleven known MAC subunits, including MAC7, indicating association between HYL1 and MAC. We propose that MAC7 links MIR transcription to pri-miRNA processing. RNA-seq analysis showed that down-regulated genes in MAC subunit mutants are mostly involved in plant defense and stimulus responses, confirming a role of MAC in biotic and abiotic stress responses. We also discovered global intron retention defects in mutants in three subunits of MAC, thus linking MAC function to splicing in Arabidopsis. © 2017 American Society of Plant Biologists. All rights reserved.

  11. A ferroan region of the lunar highlands as recorded in meteorites MAC88104 and MAC88105

    SciTech Connect

    Jolliff, B.L.; Korotev, R.L.; Haskin, L.A. )

    1991-11-01

    MacAlpine Hills 88104 and 88105 (MAC88104/5) are paired meteorites of noritic anorthosite composition from the lunar highlands. MAC88105 is a breccia composed mainly of melt-breccia clasts in a fine-grained, fragmental, and partly glassy matrix. The most abundant melt lithologies are feldspathic and are similar in composition to the bulk meteorite. Other melt lithologies include feldspathic melt rocks, mafic melt breccias, and a rare melt breccia relatively enriched in incompatible trace elements. Subordinate lithic clasts are granulitic breccias and ferroan (relatively low Mg/(Mg + Fe)) igneous lithologies, including troctolitic anorthosite, anorthositic norite, gabbronorite, and anorthosite. Igneous clasts having mafic mineral compositions more magnesian than Fo{sub 55} and En{sub 60} were not observed. Rare fragments of glass spheres and shards as well as glass clasts indicate that the meteorite was derived from an immature regolith. The bulk composition of MAC88105 is characterized by a molar Mg/(Mg + Fe) ratio of 0.62, at the extreme low end of the range for meteorites from the lunar highlands. Its low concentrations of incompatible trace elements and feldspathic bulk composition (29% Al{sub 2}O{sub 3}), suggests that it, like the other lunar meteorites, formed at a site far removed from the areas sampled by the Apollo missions. Similarities in mineral compositions among the different lithologies of the breccia and the distribution of mineral fragments suggest that most components of the meteorite were derived from a crustal section dominated by material with a noritic anorthosite composition and an affinity of the ferroan suite of plutonic rocks.

  12. The effect of nitrous oxide on the minimum alveolar concentration (MAC) and MAC derivatives of isoflurane in dogs.

    PubMed

    Voulgaris, Debra A; Egger, Christine M; Seddighi, M Reza; Rohrbach, Barton W; Love, Lydia C; Doherty, Thomas J

    2013-04-01

    This study investigated the effects of 70% nitrous oxide (N2O) on the minimum alveolar concentration (MAC) of isoflurane (ISO) that prevents purposeful movement, the MAC of ISO at which there is no motor movement (MACNM), and the MAC of ISO at which autonomic responses are blocked (MACBAR) in dogs. Six adult, healthy, mixed-breed, intact male dogs were anesthetized with ISO delivered via mask. Baseline MAC, MACNM, and MACBAR of ISO were determined for each dog using a supra-maximal electrical stimulus (50 V, 50 Hz, 10 ms). Nitrous oxide (70%) was then administered and MAC and its derivatives (N2O-MAC, N2O-MACNM, and N2O-MACBAR) were determined using the same methodology. The values for baseline MAC, MACNM, and MACBAR were 1.39 ± 0.14, 1.59 ± 0.10, and 1.72 ± 0.16, respectively. The addition of 70% N2O decreased MAC, MACNM, and MACBAR by 32%, 15%, and 25%, respectively.

  13. TreeMAC: Localized TDMA MAC protocol for real-time high-data-rate sensor networks

    USGS Publications Warehouse

    Song, W.-Z.; Huang, R.; Shirazi, B.; Husent, R.L.

    2009-01-01

    Earlier sensor network MAC protocols focus on energy conservation in low-duty cycle applications, while some recent applications involve real-time high-data-rate signals. This motivates us to design an innovative localized TDMA MAC protocol to achieve high throughput and low congestion in data collection sensor networks, besides energy conservation. TreeMAC divides a time cycle into frames and frame into slots. Parent determines children's frame assigmnent based on their relative bandwidth demand, and each node calculates its own slot assignment based on its hop-count to the sink. This innovative 2-dimensional frame-slot assignment algorithm has the following nice theory properties. Firstly, given any node, at any time slot, there is at most one active sender in its neighborhood (includ ing itself). Secondly, the packet scheduling with TreelMAC is bufferless, which therefore minimizes the probability of network congestion. Thirdly, the data throughput to gateway is at least 1/3 of the optimum assuming reliable links. Our experiments on a 24 node test bed demonstrate that TreeMAC protocol significantly improves network throughput and energy efficiency, by comparing to the TinyOS's default CSMA MAC protocol and a recent TDMA MAC protocol Funneling-MAC[8]. ?? 2009 IEEE.

  14. Modulation of the effector function of human monocytes for Mycobacterium avium by human immunodeficiency virus-1 envelope glycoprotein gp120.

    PubMed Central

    Shiratsuchi, H; Johnson, J L; Toossi, Z; Ellner, J J

    1994-01-01

    Disseminated Mycobacterium avium infection in AIDS is associated with high tissue burdens (10(9)-10(10) mycobacteria/g tissue) of organism. The basis for the extraordinary susceptibility of AIDS to M. avium infection is unclear. HIV or its constituents may alter mononuclear phagocyte functions resulting in enhanced intracellular M. avium growth. The effects of an envelope glycoprotein (gp120), a transmembrane protein (p121), and core proteins of HIV-1 on M. avium infection of human monocytes were examined. Preculturing monocytes with gp120 inhibited M. avium phagocytosis and consistently enhanced intracellular growth of six M. avium strains. Pretreatment with p121, gag5, or p24 did not inhibit phagocytosis nor enhance intracellular growth of M. avium. Incubation of gp120 with soluble CD4 before addition to monocyte cultures or pretreatment of monocytes with OKT4A abrogated gp120 effects on M. avium phagocytosis and intracellular growth. gp120 also augmented cytokine production by infected monocytes. These results suggest that gp120, but not p121 or core proteins, modulate monocyte phagocytosis and enhance intracellular growth of M. avium at least in part through monocyte CD4 receptors. Direct effects of HIV-1 products may, therefore, contribute to the diathesis of AIDS to develop disseminated M. avium infection and to the extensive replication of the organisms within tissue macrophages. Images PMID:8113420

  15. Mycobacterium avium subspecies induce differential expression of pro-inflammatory mediators in a murine macrophage model: evidence for enhanced pathogenicity of Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Basler, Tina; Geffers, Robert; Weiss, Siegfried; Valentin-Weigand, Peter; Goethe, Ralph

    2008-01-01

    Mycobacterium avium subspecies (ssp.) paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic, non-treatable granulomatous enteritis of ruminants. MAP is the only mycobacterium affecting the intestinal tract, which is of interest since it is presently the most favoured pathogen linked to Crohn's disease (CD) in humans due to its frequent detection in CD tissues. MAP is genetically closely related to other M. avium ssp. such as M. avium ssp. avium (MAA) and M. avium ssp. hominissuis (MAH) which can cause mycobacteriosis in animals and immunocompromised humans. We have recently shown that murine macrophage cell lines represent suitable systems to analyse M. avium ssp. patho-mechanisms and could show that MAP, but not MAA, specifically inhibited the antigen-specific stimulatory capacity for CD4(+) T-cells. In the present study, we compared gene expression profiles of murine RAW264.7 macrophages in response to infections with MAP or MAA using murine high-density oligonucleotide Affymetrix microarrays. A comparison of MAP and MAA infection revealed 17 differentially expressed genes. They were expressed at a much lower level in MAP-infected macrophages than in MAA-infected macrophages. Among these were the genes for IL-1beta, IL-1alpha, CXCL2, PTGS2 (COX2), lipocalin (LCN2) and TNF, which are important pro-inflammatory factors. The microarray data were confirmed for selected genes by quantitative real-time reverse transcription PCR and, by protein array analyses and ELISA. Similar to MAA, infection with MAH also showed robust induction of IL-1beta, CXCL2, COX2, LCN2 and TNF. Taken together, our results from M. avium ssp.-infected murine macrophages provide evidence that MAP in contrast to MAA and MAH specifically suppresses the pro-inflammatory defence mechanisms of infected macrophages.

  16. Application of open-source photogrammetric software MicMac for monitoring surface deformation in laboratory models

    NASA Astrophysics Data System (ADS)

    Galland, Olivier; Bertelsen, Hâvard S.; Guldstrand, Frank; Girod, Luc; Johannessen, Rikke F.; Bjugger, Fanny; Burchardt, Steffi; Mair, Karen

    2016-04-01

    Quantifying deformation is essential in modern laboratory models of geological systems. This paper presents a new laboratory monitoring method through the implementation of the open-source software MicMac, which efficiently implements photogrammetry in Structure-from-Motion algorithms. Critical evaluation is provided using results from two example laboratory geodesy scenarios: magma emplacement and strike-slip faulting. MicMac automatically processes images from synchronized cameras to compute time series of digital elevation models (DEMs) and orthorectified images of model surfaces. MicMac also implements digital image correlation to produce high-resolution displacements maps. The resolution of DEMs and displacement maps corresponds to the pixel size of the processed images. Using 24 MP cameras, the precision of DEMs and displacements is ~0.05 mm on a 40 × 40 cm surface. Processing displacement maps with Matlab® scripts allows automatic fracture mapping on the monitored surfaces. MicMac also offers the possibility to integrate 3-D models of excavated structures with the corresponding surface deformation data. The high resolution and high precision of MicMac results and the ability to generate virtual 3-D models of complex structures make it a very promising tool for quantitative monitoring in laboratory models of geological systems.

  17. The minimum alveolar concentration (MAC) of isoflurane in preterm neonates.

    PubMed

    LeDez, K M; Lerman, J

    1987-09-01

    Studies in fetal lambs suggested that the minimum alveolar concentration (MAC) in preterm neonates may be less than that in full-term neonates and older infants. To determine the MAC of isoflurane in preterm neonates, 20 patients less than 32 weeks gestation at birth and 16 patients 32-37 weeks gestation at birth, all less than 1 month post-natal age, were studied. Following tracheal intubation, the neonates were anesthetized with a predetermined end-tidal concentration of isoflurane in oxygen and air. The move-no move responses to skin incision were recorded, and MAC was determined using the "up-and-down" technique. Heart rate and systolic arterial pressure were recorded awake, before skin incision, and after skin incision. MAC (mean +/- SD) of isoflurane in preterm neonates less than 32 weeks gestation was 1.28 +/- 0.17%, and MAC in neonates 32-37 weeks gestation was 1.41 +/- 0.18% (P less than 0.05). Although heart rate did not decrease significantly in either group during the study, systolic arterial pressure decreased between 20 and 30% below awake values both before and after skin incision in both age groups (P less than 0.01). We conclude that the MAC of isoflurane in preterm neonates less than 32 weeks gestation is significantly less than that in preterm neonates 32-37 weeks gestation, and that systolic arterial pressure decreases to a similar extent at approximately 1 MAC isoflurane in both age groups.

  18. Increased NMDA receptor inhibition at an increased Sevoflurane MAC

    PubMed Central

    2012-01-01

    Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability. PMID:22672766

  19. Increased NMDA receptor inhibition at an increased Sevoflurane MAC.

    PubMed

    Brosnan, Robert J; Thiesen, Roberto

    2012-06-06

    Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

  20. Cooperative energy harvesting-adaptive MAC protocol for WBANs.

    PubMed

    Esteves, Volker; Antonopoulos, Angelos; Kartsakli, Elli; Puig-Vidal, Manel; Miribel-Català, Pere; Verikoukis, Christos

    2015-05-28

    In this paper, we introduce a cooperative medium access control (MAC) protocol, named cooperative energy harvesting (CEH)-MAC, that adapts its operation to the energy harvesting (EH) conditions in wireless body area networks (WBANs). In particular, the proposed protocol exploits the EH information in order to set an idle time that allows the relay nodes to charge their batteries and complete the cooperation phase successfully. Extensive simulations have shown that CEH-MAC significantly improves the network performance in terms of throughput, delay and energy efficiency compared to the cooperative operation of the baseline IEEE 802.15.6 standard.

  1. Cooperative Energy Harvesting-Adaptive MAC Protocol for WBANs

    PubMed Central

    Esteves, Volker; Antonopoulos, Angelos; Kartsakli, Elli; Puig-Vidal, Manel; Miribel-Català, Pere; Verikoukis, Christos

    2015-01-01

    In this paper, we introduce a cooperative medium access control (MAC) protocol, named cooperative energy harvesting (CEH)-MAC, that adapts its operation to the energy harvesting (EH) conditions in wireless body area networks (WBANs). In particular, the proposed protocol exploits the EH information in order to set an idle time that allows the relay nodes to charge their batteries and complete the cooperation phase successfully. Extensive simulations have shown that CEH-MAC significantly improves the network performance in terms of throughput, delay and energy efficiency compared to the cooperative operation of the baseline IEEE 802.15.6 standard. PMID:26029950

  2. A Hybrid MacCormack-type Scheme for Computational Aeroacoustics

    NASA Astrophysics Data System (ADS)

    Yazdani, Soroush

    A new type of MacCormack scheme, using a modified Low Dissipation and Dispersion Runge-Kutta time marching method, is presented. This scheme is using two stages in every step which implements biased spatial differencing stencils and for the remaining stages uses non-dissipative central differencing stencils. Because of using the MacCormack-type scheme in this method, the new scheme carries an inherent artificial dissipation which uses the ease of implementing boundary condition specifications of a two-stage MacCormack scheme.

  3. Handling Deafness Problem of Scheduled Multi-Channel Polling MACs

    NASA Astrophysics Data System (ADS)

    Jiang, Fulong; Liu, Hao; Shi, Longxing

    Combining scheduled channel polling with channel diversity is a promising way for a MAC protocol to achieve high energy efficiency and performance under both light and heavy traffic conditions. However, the deafness problem may cancel out the benefit of channel diversity. In this paper, we first investigate the deafness problem of scheduled multi-channel polling MACs with experiments. Then we propose and evaluate two schemes to handle the deafness problem. Our experiment shows that deafness is a significant reason for performance degradation in scheduled multi-channel polling MACs. A proper scheme should be chosen depending on the traffic pattern and the design objective.

  4. Reconstitution of the Escherichia coli macrolide transporter: the periplasmic membrane fusion protein MacA stimulates the ATPase activity of MacB.

    PubMed

    Tikhonova, Elena B; Devroy, Vishakha K; Lau, Sze Yi; Zgurskaya, Helen I

    2007-02-01

    Periplasmic membrane fusion proteins (MFPs) are essential components of the type I protein secretion systems and drug efflux pumps in Gram-negative bacteria. Previous studies suggested that MFPs connect the inner and outer membrane components of the transport systems and by this means co-ordinate the transfer of substrates across the two membranes. In this study, we purified and reconstituted the macrolide transporter MacAB from Escherichia coli. Here, MacA is a periplasmic MFP and MacB is an ABC-type transporter. Similar to other MFP-dependent transporters from E. coli, the in vivo function of MacAB requires the outer membrane channel TolC. The purified MacB displayed a basal ATPase activity in detergent micelles. This activity conformed to Michaelis-Menten kinetics but was unresponsive to substrates or accessory proteins. Upon reconstitution into proteoliposomes, the ATPase activity of MacB was strictly dependent on MacA. The catalytic efficiency of MacAB ATPase was more than 45-fold higher than the activity of MacB alone. Both the N- and C-terminal regions of MacA were essential for this activity. MacA stimulated MacB ATPase only in phospholipid bilayers and did not need the presence of macrolides. Our results suggest that MacA is a functional subunit of the MacB transporter.

  5. No holes barred: Invasion of the intestinal mucosa by Mycobacterium avium subspecies paratuberculosis

    USDA-ARS?s Scientific Manuscript database

    The infection biology of Mycobacterium avium subspecies paratuberculosis (MAP) has recently crystalized with added details surrounding intestinal invasion. The involvement of pathogen-derived effector proteins such as the major membrane protein, oxidoreductase and fibronectin attachment proteins hav...

  6. Immunogenicity of Proteome-determined Mycobacterium avium subsp. paratuberculosis-specific Proteins in Sheep with Paratuberculosis

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subspecies paratuberculosis causes paratuberculosis, a chronic granulomatous enteritis. Detecting animals with paratuberculosis infections is difficult because the currently available tools have low sensitivity and lack specificity being prone to spurious positive test results ca...

  7. A Mycobacterium avium subsp. paratuberculosis predicted serine protease is associated with acid stress and intraphagosomal survival

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen that persists inside host macrophages despite severe oxidative stress and nutrient deprivation. Intrabacterial pH homeostasis is vital to pathogenic mycobacteria to preserve cellular biological processes and stability of ...

  8. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    EPA Science Inventory

    BACKGROUND: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexis...

  9. Trypanosoma avium incidence, pathogenicity and response to melarsomine in falcons from Kuwait.

    PubMed

    Tarello, W

    2005-03-01

    Epidemiological and clinical studies on Trypanosoma avium are lacking in the Middle East. The aims of this study were to determine the T. avium incidence in falcons from Kuwait, report clinical signs and find an effective therapy. Blood smears from 921 diseased and 56 healthy falcons were examined between May 2003 and April 2004. 12 birds 11.3%) were found infected by T. avium and ten of these were treated with melarsomine (Cymelarsan) at a dosage of 0.25 mg/kg intramuscularly for four days. All affected birds presented clinical signs, including incapacity of flying high, poor appetite, lethargy, loosing weight, weakness, dyspnoea and death. Signs disappeared within 1-7 days after administration of melarsomine. Trypomastigotes were not detected in blood smears made 1-7 days after the end of therapy. This study suggests that T. avium induces disease in falcons and that melarsomine can be an effective therapy eliminating both clinical signs and circulating trypomastigotes.

  10. Composition and potency characterization of Mycobacterium avium subsp. paratuberculosis purified protein derivatives

    USDA-ARS?s Scientific Manuscript database

    Mycobacterium avium subsp. paratuberculosis (MAP) purified protein derivatives (PPDs) are immunologic reagents prepared from cultured filtrates of the type strain ATCC 19698. Traditional production consists of floating culture incubation at 37oC, organism inactivation by autoclaving, coarse filtrat...

  11. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    EPA Science Inventory

    BACKGROUND: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexis...

  12. Involvement of matrix metalloproteinases in human immunodeficiency virus type 1-induced replication by clinical Mycobacterium avium isolates.

    PubMed

    Dezzutti, C S; Swords, W E; Guenthner, P C; Sasso, D R; Wahl, L M; Drummond, A H; Newman, G W; King, C H; Quinn, F D; Lal, R B

    1999-10-01

    The role of Mycobacterium avium isolates in modulating human immunodeficiency virus type 1 (HIV-1) replication was examined by use of an in vitro, resting T cell system. Two human clinical isolates (serotypes 1 and 4) but not an environmental M. avium isolate (serotype 2) enhanced HIV-1 replication. The M. avium-induced HIV-1 replication was not associated with cell activation or differential cytokine production or utilization. Addition of matrix metalloproteinase (MMP) inhibitors and their in vivo regulators, tissue inhibitors of metalloproteinases-1 and -2, abrogated M. avium-induced HIV-1 replication 80%-95%. The MMP inhibitors did not have any effect on the HIV-1 protease activity, suggesting that they may affect cellular processes. Furthermore, MMP-9 protein was differentially expressed after infection with clinical M. avium isolates and paralleled HIV-1 p24 production. Collectively, these data suggest that M. avium-induced HIV-1 replication is mediated, in part, through the induction of MMP-9.

  13. PAD-MAC: Primary User Activity-Aware Distributed MAC for Multi-Channel Cognitive Radio Networks

    PubMed Central

    Ali, Amjad; Piran, Md. Jalil; Kim, Hansoo; Yun, Jihyeok; Suh, Doug Young

    2015-01-01

    Cognitive radio (CR) has emerged as a promising technology to solve problems related to spectrum scarcity and provides a ubiquitous wireless access environment. CR-enabled secondary users (SUs) exploit spectrum white spaces opportunistically and immediately vacate the acquired licensed channels as primary users (PUs) arrive. Accessing the licensed channels without the prior knowledge of PU traffic patterns causes severe throughput degradation due to excessive channel switching and PU-to-SU collisions. Therefore, it is significantly important to design a PU activity-aware medium access control (MAC) protocol for cognitive radio networks (CRNs). In this paper, we first propose a licensed channel usage pattern identification scheme, based on a two-state Markov model, and then estimate the future idle slots using previous observations of the channels. Furthermore, based on these past observations, we compute the rank of each available licensed channel that gives SU transmission success assessment during the estimated idle slot. Secondly, we propose a PU activity-aware distributed MAC (PAD-MAC) protocol for heterogeneous multi-channel CRNs that selects the best channel for each SU to enhance its throughput. PAD-MAC controls SU activities by allowing them to exploit the licensed channels only for the duration of estimated idle slots and enables predictive and fast channel switching. To evaluate the performance of the proposed PAD-MAC, we compare it with the distributed QoS-aware MAC (QC-MAC) and listen-before-talk MAC schemes. Extensive numerical results show the significant improvements of the PAD-MAC in terms of the SU throughput, SU channel switching rate and PU-to-SU collision rate. PMID:25831084

  14. PAD-MAC: primary user activity-aware distributed MAC for multi-channel cognitive radio networks.

    PubMed

    Ali, Amjad; Piran, Md Jalil; Kim, Hansoo; Yun, Jihyeok; Suh, Doug Young

    2015-03-30

    Cognitive radio (CR) has emerged as a promising technology to solve problems related to spectrum scarcity and provides a ubiquitous wireless access environment. CR-enabled secondary users (SUs) exploit spectrum white spaces opportunistically and immediately vacate the acquired licensed channels as primary users (PUs) arrive. Accessing the licensed channels without the prior knowledge of PU traffic patterns causes severe throughput degradation due to excessive channel switching and PU-to-SU collisions. Therefore, it is significantly important to design a PU activity-aware medium access control (MAC) protocol for cognitive radio networks (CRNs). In this paper, we first propose a licensed channel usage pattern identification scheme, based on a two-state Markov model, and then estimate the future idle slots using previous observations of the channels. Furthermore, based on these past observations, we compute the rank of each available licensed channel that gives SU transmission success assessment during the estimated idle slot. Secondly, we propose a PU activity-aware distributed MAC (PAD-MAC) protocol for heterogeneous multi-channel CRNs that selects the best channel for each SU to enhance its throughput. PAD-MAC controls SU activities by allowing them to exploit the licensed channels only for the duration of estimated idle slots and enables predictive and fast channel switching. To evaluate the performance of the proposed PAD-MAC, we compare it with the distributed QoS-aware MAC (QC-MAC) and listen-before-talk MAC schemes. Extensive numerical results show the significant improvements of the PAD-MAC in terms of the SU throughput, SU channel switching rate and PU-to-SU collision rate.

  15. Prior determination of baseline minimum alveolar concentration (MAC) of isoflurane does not influence the effect of ketamine on MAC in rabbits

    PubMed Central

    Gianotti, Giacomo; Valverde, Alexander; Sinclair, Melissa; Dyson, Doris H.; Gibson, Thomas; Johnson, Ron

    2012-01-01

    The objective of this study was to compare the effect on the minimum alveolar concentration (MAC) of isoflurane when ketamine was administered either after or without prior determination of the baseline MAC of isoflurane in rabbits. Using a prospective randomized crossover study, 8 adult, female New Zealand rabbits were allocated to 2 treatment groups. Anesthesia was induced and maintained with isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion (CRI) of 40 μg/kg BW per min, given by intravenous (IV)], which was determined after the baseline MAC of isoflurane was determined beforehand. A third MAC determination was started 30 min after stopping the CRI. Group 2 (separate-day determination) had the MAC-sparing effect of ketamine determined without previous determination of the baseline MAC of isoflurane. A second MAC determination was started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 ± 0.09%) was significantly decreased by ketamine (1.63 ± 0.07%). After stopping the CRI, the MAC was significantly less (2.04 ± 0.11%) than the baseline MAC of isoflurane and significantly greater than the MAC during the CRI. In group 2, ketamine decreased isoflurane MAC (1.53 ± 0.22%) and the MAC increased significantly (1.94 ± 0.25%) after stopping the CRI. Minimum alveolar concentration (MAC) values did not differ significantly between the groups either during ketamine administration or after stopping ketamine. Under the study conditions, prior determination of the baseline isoflurane MAC did not alter the effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for research purposes. PMID:23543951

  16. Prior determination of baseline minimum alveolar concentration (MAC) of isoflurane does not influence the effect of ketamine on MAC in rabbits.

    PubMed

    Gianotti, Giacomo; Valverde, Alexander; Sinclair, Melissa; Dyson, Doris H; Gibson, Thomas; Johnson, Ron

    2012-10-01

    The objective of this study was to compare the effect on the minimum alveolar concentration (MAC) of isoflurane when ketamine was administered either after or without prior determination of the baseline MAC of isoflurane in rabbits. Using a prospective randomized crossover study, 8 adult, female New Zealand rabbits were allocated to 2 treatment groups. Anesthesia was induced and maintained with isoflurane. Group 1 (same-day determination) had the MAC-sparing effect of ketamine [1 mg/kg bodyweight (BW) bolus followed by a constant rate infusion (CRI) of 40 μg/kg BW per min, given by intravenous (IV)], which was determined after the baseline MAC of isoflurane was determined beforehand. A third MAC determination was started 30 min after stopping the CRI. Group 2 (separate-day determination) had the MAC-sparing effect of ketamine determined without previous determination of the baseline MAC of isoflurane. A second MAC determination was started 30 min after stopping the CRI. In group 1, the MAC of isoflurane (2.15 ± 0.09%) was significantly decreased by ketamine (1.63 ± 0.07%). After stopping the CRI, the MAC was significantly less (2.04 ± 0.11%) than the baseline MAC of isoflurane and significantly greater than the MAC during the CRI. In group 2, ketamine decreased isoflurane MAC (1.53 ± 0.22%) and the MAC increased significantly (1.94 ± 0.25%) after stopping the CRI. Minimum alveolar concentration (MAC) values did not differ significantly between the groups either during ketamine administration or after stopping ketamine. Under the study conditions, prior determination of the baseline isoflurane MAC did not alter the effect of ketamine on MAC. Both methods of determining MAC seemed to be valid for research purposes.

  17. Effect of lipoarabinomannan from Mycobacterium avium subsp avium in Freund's incomplete adjuvant on the immune response of cattle

    PubMed Central

    Colavecchia, S.B.; Jolly, A.; Fernández, B.; Fontanals, A.M.; Fernández, E.; Mundo, S.L.

    2012-01-01

    The aim of the present study was to determine whether lipoarabinomannan (LAM), in combination with Freund's incomplete adjuvant (FIA), was able to improve cell-mediated and antibody-mediated immune responses against ovalbumin (OVA) in cattle. Twenty-three calves were assigned to four treatment groups, which were subcutaneously immunized with either OVA plus FIA, OVA plus FIA and LAM from Mycobacterium avium subsp avium, FIA plus LAM, or FIA alone. Lymphoproliferation, IFN-γ production and cell subpopulations on peripheral blood mononuclear cells before and 15 days after treatment were evaluated. Delayed hypersensitivity was evaluated on day 57. Specific humoral immune response was measured by ELISA. Inoculation with LAM induced higher levels of lymphoproliferation and IFN-γ production in response to ConA and OVA (P < 0.05). Specific antibody titers were similar in both OVA-immunized groups. Interestingly, our results showed that the use of LAM in vaccine preparations improved specific cell immune response evaluated by lymphoproliferation and IFN-γ production by at least 50 and 25%, respectively, in cattle without interfering with tuberculosis and paratuberculosis diagnosis. PMID:22286534

  18. Effect of lipoarabinomannan from Mycobacterium avium subsp avium in Freund's incomplete adjuvant on the immune response of cattle.

    PubMed

    Colavecchia, S B; Jolly, A; Fernández, B; Fontanals, A M; Fernández, E; Mundo, S L

    2012-02-01

    The aim of the present study was to determine whether lipoarabinomannan (LAM), in combination with Freund's incomplete adjuvant (FIA), was able to improve cell-mediated and antibody-mediated immune responses against ovalbumin (OVA) in cattle. Twenty-three calves were assigned to four treatment groups, which were subcutaneously immunized with either OVA plus FIA, OVA plus FIA and LAM from Mycobacterium avium subsp avium, FIA plus LAM, or FIA alone. Lymphoproliferation, IFN-γ production and cell subpopulations on peripheral blood mononuclear cells before and 15 days after treatment were evaluated. Delayed hypersensitivity was evaluated on day 57. Specific humoral immune response was measured by ELISA. Inoculation with LAM induced higher levels of lymphoproliferation and IFN-γ production in response to ConA and OVA (P < 0.05). Specific antibody titers were similar in both OVA-immunized groups. Interestingly, our results showed that the use of LAM in vaccine preparations improved specific cell immune response evaluated by lymphoproliferation and IFN-γ production by at least 50 and 25%, respectively, in cattle without interfering with tuberculosis and paratuberculosis diagnosis.

  19. Detection of a novel catalase in extracts of Mycobacterium avium and Mycobacterium intracellulare.

    PubMed Central

    Wayne, L G; Diaz, G A

    1988-01-01

    A novel class of catalase, which differs from the previously described M- and T-catalases of mycobacteria, was detected in strains of Mycobacterium avium and M. intracellulare. Designated A-catalase, this enzyme resisted inactivation at 68 degrees C, was inactivated by 3-amino-1,2,4-triazole (aminotriazole), and exhibited no peroxidase activity. All of these properties distinguished the enzyme from T-catalase. The A-catalase exhibited a Km of 70 mM H2O2, which is between the upper and lower extremes of the ranges reported for T- and M-catalases, respectively. The A-catalase appeared to be more hydrophobic than M-catalase and did not react with antiserum to a representative sample of this class. The banding patterns of T- and M-catalases seen by polyacrylamide gel electrophoresis (PAGE) were essentially unaffected by the incorporation of sodium dodecyl sulfate (SDS) into the PAGE system, whereas the single band of A-catalase seen by PAGE without SDS resolved into as many as five bands in the presence of SDS; these bands were all of slower mobility than the original band. The banding pattern seen with SDS appeared to be related more to counterion charge effects than to molecular size increases that could be attributed to SDS complexed to the protein. It remains to be determined whether the multiple A-catalase bands reflect different proteins or different SDS micellar complexes of a single protein. Images PMID:3346077

  20. Detection of Mycobacterium avium subsp. paratuberculosis in Drinking Water and Biofilms by Quantitative PCR ▿ †

    PubMed Central

    Beumer, Amy; King, Dawn; Donohue, Maura; Mistry, Jatin; Covert, Terry; Pfaller, Stacy

    2010-01-01

    It has been suggested that Mycobacterium avium subspecies paratuberculosis has a role in Crohn's disease. The organism may be acquired but is difficult to culture from the environment. We describe a quantitative PCR (qPCR) method to detect M. avium subsp. paratuberculosis in drinking water and the results of its application to drinking water and faucet biofilm samples collected in the United States. PMID:20817803

  1. Infection by Mycobacterium avium intracellulare in AIDS: endoscopic duodenal appearance mimicking Whipple's disease.

    PubMed

    Vázquez-Iglesias, J L; Yañez, J; Durana, J; Arnal, F

    1988-09-01

    We report the case of a 24-year-old woman who presented with diarrhea, weight loss and abdominal lymph node enlargement. A diagnosis of infection by Mycobacterium avium intracellulare with a clinical picture similar to Whipple's disease was established. The endoscopic study of the duodenum revealed multiple yellow nodules that became confluent in the second portion, entirely replacing the normal mucosa. These endoscopic findings have not been described previously in intestinal infection by Mycobacterium avium intracellulare.

  2. Use of restriction fragment length polymorphism as a genetic marker for typing Mycobacterium avium strains.

    PubMed Central

    Roiz, M P; Palenque, E; Guerrero, C; Garcia, M J

    1995-01-01

    Restriction fragment length polymorphism (RFLP) was used to study 75 clinical isolates identified as Mycobacterium avium. Two repetitive insertion sequences, IS1311 and IS900, were used as DNA probes. Although less than 25% of isolates showed RFLP patterns with IS900, all strains gave banding patterns with IS1311. M. avium strains isolated from patients with AIDS exhibited marked polymorphism with both probes. PMID:7615764

  3. Pulmonary collectins play distinct roles in host defense against Mycobacterium avium.

    PubMed

    Ariki, Shigeru; Kojima, Takashi; Gasa, Shinsei; Saito, Atsushi; Nishitani, Chiaki; Takahashi, Motoko; Shimizu, Takeyuki; Kurimura, Yuichiro; Sawada, Norimasa; Fujii, Nobuhiro; Kuroki, Yoshio

    2011-09-01

    Pulmonary collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), play important roles in the innate immunity of the lung. Mycobacterium avium is one of the well-known opportunistic pathogens that can replicate within macrophages. We examined the effects of pulmonary collectins in host defense against M. avium infection achieved via direct interaction between bacteria and collectins. Although both pulmonary collectins bound to M. avium in a Ca(2+)-dependent manner, these collectins revealed distinct ligand-binding specificity and biological activities. SP-A and SP-D bound to a methoxy group containing lipid and lipoarabinomannan, respectively. Binding of SP-D but not SP-A resulted in agglutination of M. avium. A chimeric protein with the carbohydrate recognition domain of SP-D, which chimera revealed a bouquet-like arrangement similar to SP-A, also agglutinated M. avium. The ligand specificity of the carbohydrate recognition domain of SP-D seems to be necessary for agglutination activity. The binding of SP-A strongly inhibited the growth of M. avium in culture media. Although pulmonary collectins did not increase membrane permeability of M. avium, they attenuated the metabolic rate of the bacteria. Observations under a scanning electron microscope revealed that SP-A almost completely covers bacterial surfaces, whereas SP-D binds to certain areas like scattered dots. These observations suggest that a distinct binding pattern of collectins correlates with the difference of their biological activities. Furthermore, the number of bacteria phagocytosed by macrophages was significantly increased in the presence of SP-D. These data indicate that pulmonary collectins play critical roles in host defense against M. avium.

  4. Competition at the Wireless Sensor Network MAC Layer: Low Power Probing interfering with X-MAC

    NASA Astrophysics Data System (ADS)

    Zacharias, Sven; Newe, Thomas

    2011-08-01

    Wireless Sensor Networks (WSNs) combine sensors with computer networks and enable very dense, in-situ and live measurements of data over a large area. Since this emerging technology has the potential to be embedded almost everywhere for numberless applications, interference between different networks can become a serious issue. For most WSNs, it is assumed today that the network medium access is non-competitive. On the basis of X-MAC interfered by Low Power Probing, this paper shows the danger and the effects of different sensor networks communicating on a single wireless channel of the 2.4 GHz band, which is used by the IEEE 802.15.4 standard.

  5. Operational effectiveness of a Multiple Aquila Control System (MACS)

    NASA Technical Reports Server (NTRS)

    Brown, R. W.; Flynn, J. D.; Frey, M. R.

    1983-01-01

    The operational effectiveness of a multiple aquila control system (MACS) was examined under a variety of remotely piloted vehicle (RPV) mission configurations. The set of assumptions and inputs used to form the rules under which a computerized simulation of MACS was run is given. The characteristics that are to govern MACS operations include: the battlefield environment that generates the requests for RPV missions, operating time-lines of the RPV-peculiar equipment, maintenance requirements, and vulnerability to enemy fire. The number of RPV missions and the number of operation days are discussed. Command, control, and communication data rates are estimated by determining how many messages are passed and what information is necessary in them to support ground coordination between MACS sections.

  6. 5. Photocopy of drawing of Mac Dougall furnace in roaster ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Photocopy of drawing of Mac Dougall furnace in roaster building from John L. Bray, The Principles of Metallurgy Ginn & Co., New York, 1929. - International Smelting & Refining Company, Tooele Smelter, Roaster Building, State Route 178, Tooele, Tooele County, UT

  7. MAC mini acceptance test procedure, software Version 3.0

    SciTech Connect

    Russell, V.K.

    1994-10-17

    The K Basins Materials Accounting (MAC) programs had some major improvements made to it to organize the main-tables by Location, Canister, and Material. This ATP describes how the code was to be tested to verify its correctness.

  8. MacSPOC: Orbital trajectory calculations on a laptop computer

    NASA Technical Reports Server (NTRS)

    Adamo, Dan

    1991-01-01

    Orbital trajectory calculations on a laptop computer are presented in the form of the viewgraphs. The following subject areas are covered: laptop computing in the Space Shuttle program; current laptop prototyping with MacSPOC; future laptop applications; and summary.

  9. Aeronautical Mobile Airport Communications System (AeroMACS)

    NASA Technical Reports Server (NTRS)

    Budinger, James M.; Hall, Edward

    2011-01-01

    To help increase the capacity and efficiency of the nation s airports, a secure wideband wireless communications system is proposed for use on the airport surface. This paper provides an overview of the research and development process for the Aeronautical Mobile Airport Communications System (AeroMACS). AeroMACS is based on a specific commercial profile of the Institute of Electrical and Electronics Engineers (IEEE) 802.16 standard known as Wireless Worldwide Interoperability for Microwave Access or WiMAX (WiMax Forum). The paper includes background on the need for global interoperability in air/ground data communications, describes potential AeroMACS applications, addresses allocated frequency spectrum constraints, summarizes the international standardization process, and provides findings and recommendations from the world s first AeroMACS prototype implemented in Cleveland, Ohio, USA.

  10. MAC to VAX Connectivity: Heartrate Spectral Analysis System

    NASA Technical Reports Server (NTRS)

    Rahman, Hasan H.; Faruque, Monazer

    1993-01-01

    The heart rate Spectral Analysis System (SAS) acquires and analyzes, in real-time, the Space Shuttle onboard electrocardiograph (EKG) experiment signals, calculates the heartrate, and applies a Fast Fourier Transformation (FFT) to the heart rate. The system also calculates other statistical parameters such as the 'mean heart rate' over specific time period and heart rate histogram. This SAS is used by NASA Principal Investigators as a research tool to determine the effects of weightlessness on the human cardiovascular system. This is also used to determine if Lower Body Negative Pressure (LBNP) is an effective countermeasure to the orthostatic intolerance experienced by astronauts upon return to normal gravity. In microgravity, astronauts perform the LBNP experiment in the mid deck of the Space Shuttle. The experiment data are downlinked by the orbiter telemetry system, then processed and analyzed in real-time by the integrated Life Sciences Data Acquisition (LSDS) - Spectral Analysis System. The data system is integrated within the framework of two different computer systems, VAX and Macintosh (Mac), using the networking infrastructure to assist the investigators in further understanding the most complex machine on Earth--the human body.

  11. Maximum growth rate of Mycobacterium avium in continuous culture or chronically infected BALB/c mice.

    PubMed

    McCarthy, C M; Taylor, M A; Dennis, M W

    1987-01-01

    Mycobacterium avium is a human pathogen which may cause either chronic or disseminated disease and the organism exhibits a slow rate of growth. This study provides information on the growth rate of the organism in chronically infected mice and its maximal growth rate in vitro. M. avium was grown in continuous culture, limited for nitrogen with 0.5 mM ammonium chloride and dilution rates that ranged from 0.054 to 0.153 h-1. The steady-state concentration of ammonia nitrogen and M. avium cells for each dilution rate were determined. The bacterial saturation constant for growth-limiting ammonia was 0.29 mM (4 micrograms nitrogen/ml) and, from this, the maximal growth rate for M. avium was estimated to be 0.206 h-1 or a doubling time of 3.4 h. BALB/c mice were infected intravenously with 3 x 10(6) colony-forming units and a chronic infection resulted, typical of virulent M. avium strains. During a period of 3 months, the number of mycobacteria remained constant in the lungs, but increased 30-fold and 8,900-fold, respectively, in the spleen and mesenteric lymph nodes. The latter increase appeared to be due to proliferation in situ. The generation time of M. avium in the mesenteric lymph nodes was estimated to be 7 days.

  12. Biologically distinct subtypes of Mycobacterium avium differ in possession of insertion sequence IS901.

    PubMed

    Kunze, Z M; Portaels, F; McFadden, J J

    1992-09-01

    Mycobacterium avium causes disease, principally tuberculosis in immunocompromised individuals. It is the most frequent cause of disseminated infections in AIDS patients in the West. The pathogen is also associated with disease in animals, chiefly birds and livestock, and may be isolated from environmental samples such as soil and water. Analysis of strains of M. avium isolated from clinical, veterinary, and environmental sources for the presence of the mycobacterial insertion sequences IS900 and IS901 demonstrates the specific association of IS901 to animal pathogenic M. avium strains. In contrast, most clinical M. avium strains and all AIDS-derived strains examined so far lacked IS901. Significant differences in the plasmid contents and serotypes of strains with and without IS901 were also found. We therefore suggest that the presence of IS901 divides M. avium into two clearly distinct subtypes with differing host range, virulence, plasmid possession, and serotyping antigens. By using DNA sequence data from IS901 and M. avium DNA, a set of polymerase chain reactions were developed for the specific detection and differentiation of these subtypes.

  13. Maximizing Capture Efficiency and Specificity of Magnetic Separation for Mycobacterium avium subsp. paratuberculosis Cells ▿

    PubMed Central

    Foddai, Antonio; Elliott, Christopher T.; Grant, Irene R.

    2010-01-01

    In order to introduce specificity for Mycobacterium avium subsp. paratuberculosis prior to a phage amplification assay, various magnetic-separation approaches, involving either antibodies or peptides, were evaluated in terms of the efficiency of capture (expressed as a percentage) of M. avium subsp. paratuberculosis cells and the percentage of nonspecific binding by other Mycobacterium spp. A 50:50 mixture of MyOne Tosylactivated Dynabeads coated with the chemically synthesized M. avium subsp. paratuberculosis-specific peptides biotinylated aMp3 and biotinylated aMptD (i.e., peptide-mediated magnetic separation [PMS]) proved to be the best magnetic-separation approach for achieving 85 to 100% capture of M. avium subsp. paratuberculosis and minimal (<1%) nonspecific recovery of other Mycobacterium spp. (particularly if beads were blocked with 1% skim milk before use) from broth samples containing 103 to 104 CFU/ml. When PMS was coupled with a recently optimized phage amplification assay and used to detect M. avium subsp. paratuberculosis in 50-ml volumes of spiked milk, the mean 50% limit of detection (LOD50) was 14.4 PFU/50 ml of milk (equivalent to 0.3 PFU/ml). This PMS-phage assay represents a novel, rapid method for the detection and enumeration of viable M. avium subsp. paratuberculosis organisms in milk, and potentially other sample matrices, with results available within 48 h. PMID:20851966

  14. A tribute to Lloyd D. MacLean.

    PubMed

    Keith, Roger G

    2015-08-01

    Dr. Lloyd D. MacLean, long-time co-editor of the Canadian Journal of Surgery passed away earlier this year at the age of 90. In order to appreciate the contributions of Dr. MacLean to the journal, this commentary recognizes him as a humble surgeon–scientist who was one of — if not the — most outstanding Canadian ambassadors to academic surgery in North America.

  15. Conformal holonomy in MacDowell-Mansouri gravity

    SciTech Connect

    Reid, James A.; Wang, Charles H.-T.

    2014-03-15

    The MacDowell-Mansouri formulation of general relativity is based on a gauge theory whose gauge algebra depends on the sign of the cosmological constant. In this article, we show that the gauge algebra is uniquely determined by the conformal structure of spacetime itself. Specifically, we show that in vacuum: the spacetime conformal holonomy algebra coincides with the MacDowell-Mansouri gauge algebra for both signs of the cosmological constant, in both Lorentzian and Euclidean metric signatures.

  16. A tribute to Lloyd D. MacLean

    PubMed Central

    Keith, Roger G.

    2015-01-01

    Summary Dr. Lloyd D. MacLean, long-time co-editor of the Canadian Journal of Surgery passed away earlier this year at the age of 90. In order to appreciate the contributions of Dr. MacLean to the journal, this commentary recognizes him as a humble surgeon–scientist who was one of — if not the — most outstanding Canadian ambassadors to academic surgery in North America. PMID:26204372

  17. Comparative genome analyses of Mycobacterium avium reveal genomic features of its subspecies and strains that cause progression of pulmonary disease

    PubMed Central

    Uchiya, Kei-ichi; Tomida, Shuta; Nakagawa, Taku; Asahi, Shoki; Nikai, Toshiaki; Ogawa, Kenji

    2017-01-01

    Pulmonary disease caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Mycobacterium avium is the most clinically significant NTM species in humans and animals, and comprises four subspecies: M. avium subsp. avium (MAA), M. avium subsp. silvaticum (MAS), M. avium subsp. paratuberculosis (MAP), and M. avium subsp. hominissuis (MAH). To improve our understanding of the genetic landscape and diversity of M. avium and its role in disease, we performed a comparative genome analysis of 79 M. avium strains. Our analysis demonstrated that MAH is an open pan-genome species. Phylogenetic analysis based on single nucleotide variants showed that MAH had the highest degree of sequence variability among the subspecies, and MAH strains isolated in Japan and those isolated abroad possessed distinct phylogenetic features. Furthermore, MAP strains, MAS and MAA strains isolated from birds, and many MAH strains that cause the progression of pulmonary disease were grouped in each specific cluster. Comparative genome analysis revealed the presence of genetic elements specific to each lineage, which are thought to be acquired via horizontal gene transfer during the evolutionary process, and identified potential genetic determinants accounting for the pathogenic and host range characteristics of M. avium. PMID:28045086

  18. Imidazo[1,2-a]Pyridine-3-Carboxamides Are Active Antimicrobial Agents against Mycobacterium avium Infection In Vivo

    PubMed Central

    Moraski, Garrett C.; Cheng, Yong; Cho, Sanghyun; Cramer, Jeffrey W.; Godfrey, Alexander; Masquelin, Thierry; Franzblau, Scott G.; Miller, Marvin J.

    2016-01-01

    A panel of six imidazo[1,2-a]pyridine-3-carboxamides (IAPs) were shown to have low-micromolar activity against Mycobacterium avium strains. Compound ND-10885 (compound 2) showed significant activity in the lung, spleen, and liver in a mouse M. avium infection model. A combined regimen consisting of ND-10885 (compound 2) and rifampin was additive in its anti-M. avium activity in the lung. Our data indicate that IAPs represent a new class of antibiotics that are active against M. avium and could potentially serve as an effective addition to a combined treatment regimen. PMID:27216051

  19. Rifabutin

    MedlinePlus

    ... helps to prevent or slow the spread of Mycobacterium avium complex (MAC) disease in patients with human ... or have ever had blood disorders or active tuberculosis.tell your doctor if you are pregnant, plan ...

  20. 42 CFR 423.2062 - Applicability of policies not binding on the ALJ and MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and MAC. 423.2062 Section 423.2062 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2062 Applicability of policies not binding on the ALJ and MAC. (a) ALJs and the MAC are not bound by CMS program guidance, such as program...

  1. 42 CFR 423.2108 - MAC Actions when request for review is filed.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false MAC Actions when request for review is filed. 423... Hearings, MAC review, and Judicial Review § 423.2108 MAC Actions when request for review is filed. (a) General. Except as specified in paragraph (c) of this section, when an enrollee requests that the MAC...

  2. 42 CFR 423.2102 - Request for MAC review when ALJ issues decision or dismissal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Request for MAC review when ALJ issues decision or... Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2102 Request for MAC review when ALJ issues decision or dismissal. (a)(1) An enrollee to the ALJ hearing may request a MAC review if the enrollee files...

  3. 42 CFR 423.2050 - Removal of a hearing request from an ALJ to the MAC.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Removal of a hearing request from an ALJ to the MAC..., ALJ Hearings, MAC review, and Judicial Review § 423.2050 Removal of a hearing request from an ALJ to the MAC. If a request for hearing is pending before an ALJ, the MAC may assume responsibility for...

  4. 42 CFR 423.2110 - MAC reviews on its own motion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false MAC reviews on its own motion. 423.2110 Section 423... (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Reopening, ALJ Hearings, MAC review, and Judicial Review § 423.2110 MAC reviews on its own motion. (a) General rule. The MAC may decide on...

  5. Mycobacterium avium subspecies paratuberculosis, Crohn's disease and the Doomsday scenario

    PubMed Central

    Hermon-Taylor, John

    2009-01-01

    Johne's disease is chronic inflammation of the intestine caused by Mycobacterium avium subspecies paratuberculosis. Infection and disease are mainly in domestic livestock but can affect many species including primates. Johne's is a new disease which emerged at the turn of the 19th and 20th centuries and principally involved Europe and North America. It has since spread to former low incidence regions to become a global problem. Crohn's disease is a chronic inflammation of the intestine in humans which emerged in Europe and North America mid 20th century and increased to become a major healthcare problem. It has now spread to former low incidence regions. Infected animals shed Mycobacterium avium subspecies paratuberculosis in milk and into the environment. Human populations are widely exposed. Outcomes maybe influenced by microbial phenotype. Exposure to extracellular forms of these pathogens may confer some natural protection; exposure to intracellular forms which have passaged through milk macrophages or environmental protists may pose a greater threat to humans particularly individuals with an inherited or acquired susceptibility. Hot spots of human disease such as in Winnipeg which sits on rock at the junction of two rivers may result from local exposure to high levels of waterborne pathogens brought down from farmland. When appropriate methods are used most people with Crohn's disease are found to be infected. There are no data which demonstrate that these pathogens are harmless to humans. An overwhelming balance of probability and Public health risk favours the conclusion that Mycobacterium avium subspecies paratuberculosis is also pathogenic for people. A two tier co-operative pathogenic mechanism is proposed in Crohn's disease. Intracellular infection with the primary pathogen widely distributed throughout the gut causes an immune dysregulation and a specific chronic enteric neuropathy with loss of mucosal integrity. Segments of gross inflammatory disease

  6. The MacGyver effect: alive and well in health services research?

    PubMed Central

    2011-01-01

    Background In a manner similar to the television action hero MacGyver, health services researchers need to respond to the pressure of unpredictable demands and constrained time frames. The results are often both innovative and functional, with the creation of outputs that could not have been anticipated in the initial planning and design of the research. Discussion In the conduct of health services research many challenges to robust research processes are generated as a result of the interface between academic research, health policy and implementation agendas. Within a complex and rapidly evolving environment the task of the health services researcher is, therefore, to juggle sometimes contradictory pressures to produce valid results. Summary This paper identifies the MacGyver-type dilemmas which arise in health services research, wherein innovation may be called for, to maintain the intended scientific method and rigour. These 'MacGyver drivers' are framed as opposing issues from the perspective of both academic and public policy communities. The ideas expressed in this paper are illustrated by four examples from research projects positioned at the interface between public policy strategy and academia. PMID:21929826

  7. The MacGyver effect: alive and well in health services research?

    PubMed

    Perera, Roshan; Moriarty, Helen J

    2011-09-20

    In a manner similar to the television action hero MacGyver, health services researchers need to respond to the pressure of unpredictable demands and constrained time frames. The results are often both innovative and functional, with the creation of outputs that could not have been anticipated in the initial planning and design of the research. In the conduct of health services research many challenges to robust research processes are generated as a result of the interface between academic research, health policy and implementation agendas. Within a complex and rapidly evolving environment the task of the health services researcher is, therefore, to juggle sometimes contradictory pressures to produce valid results. This paper identifies the MacGyver-type dilemmas which arise in health services research, wherein innovation may be called for, to maintain the intended scientific method and rigour. These 'MacGyver drivers' are framed as opposing issues from the perspective of both academic and public policy communities. The ideas expressed in this paper are illustrated by four examples from research projects positioned at the interface between public policy strategy and academia.

  8. Magnetically assisted chemical separation (MACS) process: Preparation and optimization of particles for removal of transuranic elements

    SciTech Connect

    Nunez, L.; Kaminski, M.; Bradley, C.; Buchholz, B.A.; Aase, S.B.; Tuazon, H.E.; Vandegrift, G.F.; Landsberger, S.

    1995-05-01

    The Magnetically Assisted Chemical Separation (MACS) process combines the selectivity afforded by solvent extractants with magnetic separation by using specially coated magnetic particles to provide a more efficient chemical separation of transuranic (TRU) elements, other radionuclides, and heavy metals from waste streams. Development of the MACS process uses chemical and physical techniques to elucidate the properties of particle coatings and the extent of radiolytic and chemical damage to the particles, and to optimize the stages of loading, extraction, and particle regeneration. This report describes the development of a separation process for TRU elements from various high-level waste streams. Polymer-coated ferromagnetic particles with an adsorbed layer of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) diluted with tributyl phosphate (TBP) were evaluated for use in the separation and recovery of americium and plutonium from nuclear waste solutions. Due to their chemical nature, these extractants selectively complex americium and plutonium contaminants onto the particles, which can then be recovered from the solution by using a magnet. The partition coefficients were larger than those expected based on liquid[liquid extractions, and the extraction proceeded with rapid kinetics. Extractants were stripped from the particles with alcohols and 400-fold volume reductions were achieved. Particles were more sensitive to acid hydrolysis than to radiolysis. Overall, the optimization of a suitable NMCS particle for TRU separation was achieved under simulant conditions, and a MACS unit is currently being designed for an in-lab demonstration.

  9. Molecular Epidemiology of Mycobacterium avium subsp. paratuberculosis on Dairy Farms.

    PubMed

    Li, Lingling; Katani, Robab; Schilling, Megan; Kapur, Vivek

    2016-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the etiological agent of severe chronic intestinal inflammatory disease in ruminants, termed Johne's disease, and can infect many other animal species, including humans. MAP has a long incubation period prior to manifestation of clinical signs including diarrhea, weight loss, and loss of production. MAP has a high prevalence in dairy herds and results in considerable adverse impacts on animal health and productivity throughout the world. Recent investigations have leveraged the characterization of the MAP genome for the development of powerful new molecular techniques for MAP strain differentiation. These approaches are providing key insights into the epidemiology and transmission of MAP on and between dairy herds. We summarize the state of the art for MAP diagnostics and strain differentiation and our current knowledge of mechanisms of within- and between-herd transmission of MAP, along with future needs for the development of rational MAP infection control programs.

  10. Emphysematous pyometra secondary to Enterococcus avium infection in a dog.

    PubMed

    Chang, An-Chi; Cheng, Ching-Chang; Wang, Hsien-Chi; Lee, Wei-Ming; Shyu, Ching-Lin; Lin, Cheng-Chung; Chen, Kuan-Sheng

    2016-06-16

    A 5-year-old female intact Mastiff dog was presented with a history of vaginal discharge for 1 day. Physical examination revealed a sanguineo-purulent vaginal discharge and systemic inflammatory response syndrome. Abdominal radiographs showed several dilated and gas- filled tubular loops. The differential diagnoses included emphysematous pyometra or small intestinal mechanical ileus. Surgical exploration of the abdomen demonstrated a severely dilated and gas-filled uterus, and emphysematous pyometra was confirmed. The patient's clinical signs resolved after ovariohysterectomy. Histopathology revealed mild endometrial cystic hyperplasia with infiltration of inflammatory cells in the superficial endometrial epithelia. Enterococcus avium, an α-hemolytic gram-positive coccus, was isolated from the uterus. This paper highlights the radiographic features of emphysematous pyometra and a pathogen that has never been reported to be associated with canine pyometra previously.

  11. Understanding Mycobacterium avium subspecies hominissuis microaggregate mediated pathogenesis.

    PubMed

    Leite, Fernando Lopes Leivas

    2015-01-01

    Mycobacterium avium subspecies hominissuis (MAH) is an opportunistic pathogen and causes nontuberculous infections in immune compromised individuals, an emerging problem that has been recognized worldwide. Understanding the pathogenesis of this organism is important as better treatment and prevention options are needed. Microaggregates form when two or more bacterial cells join at a surface. MAH forms micgroaggregates to promote its entry in to epithelial cells and cause infection. The mechanisms involved in the interaction between the microaggregate and the host are becoming clearer as the molecules involved in this process are being uncovered. Microaggregate Invasion Protein-1 (MIP-1) is now described as having a major role in the invasion of epithelial cells by MAH.

  12. Phosphoenolpyruvate carboxykinase in cherry (Prunus avium L.) fruit during development.

    PubMed

    Walker, Robert P; Battistelli, Alberto; Moscatello, Stefano; Chen, Zhi-Hui; Leegood, Richard C; Famiani, Franco

    2011-11-01

    In this study the abundance and location of phosphoenolpyruvate carboxykinase (PEPCK) was determined in the flesh and skin of the sweet cherry (Prunus avium L.) cultivar Durone Nero II during development. PEPCK was not present in young fruit but appeared in both tissues as the fruit increased in size. In these there was no net dissimilation of malic acid, which accounts for the bulk of their organic acid contents when PEPCK was present. To assist in understanding the function of PEPCK, the abundance of a number of other enzymes was determined. These enzymes were aspartate aminotransferase (AspAT), glutamine synthetase (GS), phosphoenolpyruvate carboxylase (PEPC), pyruvate, orthophosphate dikinase (PPDK), and ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco). A potential role for PEPCK in the regulation of pH and the utilization of malate in gluconeogenesis in the flesh and skin of cherries is presented.

  13. Influence of cultivar and processing on cherry (Prunus avium) allergenicity.

    PubMed

    Primavesi, L; Brenna, O V; Pompei, C; Pravettoni, V; Farioli, L; Pastorello, E A

    2006-12-27

    Oral allergy syndrome is an immediate food allergic event that affects lips, mouth, and pharynx, is often triggered by fruits and vegetables, and may be associated with pollinosis. Here, we report on the allergenic pattern of different varieties of cherry (Prunus avium) and results obtained by applying several technological processes to the selected varieties. Whole cherries were submitted to chemical peeling, thermal treatment, and syruping processes, and the relative protein extracts were analyzed by in vitro (sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis) and in vivo tests (skin prick test). Electrophoretic analyses demonstrated that there was no marked difference among cherry cultivars. Chemical peeling successfully removed Pru av 3, a lipid transfer protein (LTP) responsible for oral allergy syndrome in patients without pollinosis, leading to the industrial production of cherry hypoallergenic derivatives. Furthermore, the syruping process removed almost all allergenic proteins to whom patients with pollinosis are responsive. In vivo tests confirmed electrophoretic results.

  14. Primary transcriptomes of Mycobacterium avium subsp. paratuberculosis reveal proprietary pathways in tissue and macrophages

    PubMed Central

    2010-01-01

    Background Mycobacterium avium subsp. paratuberculosis (MAP) persistently infects intestines and mesenteric lymph nodes leading to a prolonged subclinical disease. The MAP genome sequence was published in 2005, yet its transcriptional organization in natural infection is unknown. While prior research analyzed regulated gene sets utilizing defined, in vitro stress related or advanced surgical methods with various animal species, we investigated the intracellular lifestyle of MAP in the intestines and lymph nodes to understand the MAP pathways that function to govern this persistence. Results Our transcriptional analysis shows that 21%, 8% and 3% of the entire MAP genome was represented either inside tissues, macrophages or both, respectively. Transcripts belonging to latency and cell envelope biogenesis were upregulated in the intestinal tissues whereas those belonging to intracellular trafficking and secretion were upregulated inside the macrophages. Transcriptomes of natural infection and in vitro macrophage infection shared genes involved in transcription and inorganic ion transport and metabolism. MAP specific genes within large sequence polymorphisms of ancestral M. avium complex were downregulated exclusively in natural infection. Conclusions We have unveiled common and unique MAP pathways associated with persistence, cell wall biogenesis and virulence in naturally infected cow intestines, lymph nodes and in vitro infected macrophages. This dichotomy also suggests that in vitro macrophage models may be insufficient in providing accurate information on the events that transpire during natural infection. This is the first report to examine the primary transcriptome of MAP at the local infection site (i.e. intestinal tissue). Regulatory pathways that govern the lifecycle of MAP appear to be specified by tissue and cell type. While tissues show a "shut-down" of major MAP metabolic genes, infected macrophages upregulate several MAP specific genes along with a

  15. Anaesthesia with sevoflurane in pigeons: minimal anaesthetic concentration (MAC) determination and investigation of cardiorespiratory variables at 1 MAC.

    PubMed

    Botman, J; Gabriel, F; Dugdale, A H A; Vandeweerd, J-M

    2016-05-28

    The objective of the study was to determine the minimal anaesthetic concentration (MAC) of sevoflurane (SEVO) in pigeons and investigate the effects of 1 MAC SEVO anaesthesia on cardiovascular and respiratory variables compared with the awake state. This is a prospective, experimental study. Animals were seven healthy adult pigeons. After acclimatisation to handling, heart rate (HR), heart rhythm, respiratory rate (fR), end-expired carbon dioxide tension (PE'CO2), inspired CO2 tension, indirect systolic arterial blood pressure (SAP) and cloacal temperature were measured to determine baseline, 'awake' values. Pigeons were then anaesthetised with SEVO and MAC was determined by the 'bracketing' method. The same variables were monitored during a 40 minute period at 1.0 MAC SEVO for each bird. Mean MAC was 3.0±0.6 per cent for SEVO. During maintenance of anaesthesia at 1.0 MAC, SAP decreased significantly (P<0.001) without any significant change in HR. Although PE'CO2 increased significantly (P=0.001) despite an increase in fR, awake PE'CO2 values were unexpectedly low. Sinus arrhythmias were detected in two birds under SEVO anaesthesia. The times to tracheal intubation and to recovery were 2.5±0.7 and 6.4±1.7 minutes, respectively. Recovery was rapid and uneventful in all birds. In conclusion, SEVO is suitable for anaesthesia in pigeons. British Veterinary Association.

  16. Metal worker's lung: spatial association with Mycobacterium avium.

    PubMed

    James, Phillip L; Cannon, Julie; Barber, Christopher M; Crawford, Laura; Hughes, Heather; Jones, Meinir; Szram, Joanna; Cowman, Steven; Cookson, William O C; Moffatt, Miriam F; Cullinan, Paul

    2017-08-29

    Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak. After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone. Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers. MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium. We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Bayesian kriging of seroprevalence to Mycobacterium avium subspecies paratuberculosis and Neospora caninum in Alberta beef and dairy cattle.

    PubMed

    Thompson, James A; Scott, H Morgan

    2007-12-01

    Identifying spatial patterns of risk is important in the study of diseases with ecologic causes. Furthermore, relatively complex hierarchical modeling is required to determine how factors that are organized across levels interact, such as how an ecologic cause interacts with farm management and with animal characteristics. The objective of this study was to map the risk for Mycobacterium avium subspecies paratuberculosis (MAP - the causative agent of Johne's disease) and Neospora caninum (NC - the cause of neosporosis) infections in Alberta beef and dairy cattle. This objective utilized Bayesian generalized linear kriging to partition herd effects into a portion attributable to location and a portion that was independent of location. Seropositivity to NC in beef cattle showed strong support for spatial covariance, suggesting that ecologic causes were important for beef cattle but not dairy cattle. There was little evidence of spatial covariance for MAP seropositivity in either beef or dairy cattle.

  18. Bayesian kriging of seroprevalence to Mycobacterium avium subspecies paratuberculosis and Neospora caninum in Alberta beef and dairy cattle

    PubMed Central

    Thompson, James A.; Scott, H. Morgan

    2007-01-01

    Identifying spatial patterns of risk is important in the study of diseases with ecologic causes. Furthermore, relatively complex hierarchical modeling is required to determine how factors that are organized across levels interact, such as how an ecologic cause interacts with farm management and with animal characteristics. The objective of this study was to map the risk for Mycobacterium avium subspecies paratuberculosis (MAP — the causative agent of Johne’s disease) and Neospora caninum (NC — the cause of neosporosis) infections in Alberta beef and dairy cattle. This objective utilized Bayesian generalized linear kriging to partition herd effects into a portion attributable to location and a portion that was independent of location. Seropositivity to NC in beef cattle showed strong support for spatial covariance, suggesting that ecologic causes were important for beef cattle but not dairy cattle. There was little evidence of spatial covariance for MAP seropositivity in either beef or dairy cattle. PMID:18189052

  19. Influence of prior determination of baseline minimum alveolar concentration (MAC) of isoflurane on the effect of ketamine on MAC in dogs.

    PubMed

    Gianotti, Giacomo; Valverde, Alexander; Johnson, Ron; Sinclair, Melissa; Gibson, Thomas; Dyson, Doris H

    2014-07-01

    The objective of this study was to determine if prior measurement of the minimum alveolar concentration (MAC) of isoflurane influences the effect of ketamine on the MAC of isoflurane in dogs. Eight mixed-breed dogs were studied on 2 occasions. Anesthesia was induced and maintained using isoflurane. In group 1 the effect of ketamine on isoflurane MAC was determined after initially finding the baseline isoflurane MAC. In group 2, the effect of ketamine on isoflurane MAC was determined without previous measure of the baseline isoflurane MAC. In both groups, MAC was determined again 30 min after stopping the CRI of ketamine. Plasma ketamine concentrations were measured during MAC determinations. In group 1, baseline MAC (mean ± SD: 1.18 ± 0.14%) was decreased by ketamine (0.88 ± 0.14%; P < 0.05). The MAC after stopping ketamine was similar (1.09 ± 0.16%) to baseline MAC and higher than with ketamine (P < 0.05). In group 2, the MAC with ketamine (0.79 ± 0.11%) was also increased after stopping ketamine (1.10 ± 0.17%; P < 0.05). The MAC values with ketamine were different between groups (P < 0.05). Ketamine plasma concentrations were similar between groups during the events of MAC determination. The MAC of isoflurane during the CRI of ketamine yielded different results when methods of same day (group-1) versus separate days (group-2) are used, despite similar plasma ketamine concentrations with both methods. However, because the magnitude of this difference was less than 10%, either method of determining MAC is deemed acceptable for research purposes.

  20. Influence of prior determination of baseline minimum alveolar concentration (MAC) of isoflurane on the effect of ketamine on MAC in dogs

    PubMed Central

    Gianotti, Giacomo; Valverde, Alexander; Johnson, Ron; Sinclair, Melissa; Gibson, Thomas; Dyson, Doris H.

    2014-01-01

    The objective of this study was to determine if prior measurement of the minimum alveolar concentration (MAC) of isoflurane influences the effect of ketamine on the MAC of isoflurane in dogs. Eight mixed-breed dogs were studied on 2 occasions. Anesthesia was induced and maintained using isoflurane. In group 1 the effect of ketamine on isoflurane MAC was determined after initially finding the baseline isoflurane MAC. In group 2, the effect of ketamine on isoflurane MAC was determined without previous measure of the baseline isoflurane MAC. In both groups, MAC was determined again 30 min after stopping the CRI of ketamine. Plasma ketamine concentrations were measured during MAC determinations. In group 1, baseline MAC (mean ± SD: 1.18 ± 0.14%) was decreased by ketamine (0.88 ± 0.14%; P < 0.05). The MAC after stopping ketamine was similar (1.09 ± 0.16%) to baseline MAC and higher than with ketamine (P < 0.05). In group 2, the MAC with ketamine (0.79 ± 0.11%) was also increased after stopping ketamine (1.10 ± 0.17%; P < 0.05). The MAC values with ketamine were different between groups (P < 0.05). Ketamine plasma concentrations were similar between groups during the events of MAC determination. The MAC of isoflurane during the CRI of ketamine yielded different results when methods of same day (group-1) versus separate days (group-2) are used, despite similar plasma ketamine concentrations with both methods. However, because the magnitude of this difference was less than 10%, either method of determining MAC is deemed acceptable for research purposes. PMID:24982552

  1. LAMP technology: Rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Trangoni, Marcos D.; Gioffré, Andrea K.; Cerón Cucchi, María E.; Caimi, Karina C.; Ruybal, Paula; Zumárraga, Martín J.; Cravero, Silvio L.

    2015-01-01

    In this study, we developed new sets of primers to detect Brucella spp. and M. avium subsp. paratuberculosis (MAP) through isothermal amplification. We selected a previously well-characterized target gene, bscp31, specific for Brucella spp. and IS900 for MAP. The limits of detection using the loop-mediated isothermal amplification (LAMP) protocols described herein were similar to those of conventional PCR targeting the same sequences. Hydroxynaphtol blue and SYBR GreenTM allowed direct naked-eye detection with identical sensitivity as agarose gel electrophoresis. We included the LAMP-based protocol in a rapid identification scheme of the respective pathogens, and all tested isolates were correctly identified within 2 to 3 h. In addition, both protocols were suitable for specifically identifying the respective pathogens; in the case of Brucella, it also allowed the identification of all the biovars tested. We conclude that LAMP is a suitable rapid molecular typing tool that could help to shorten the time required to identify insidious bacteria in low-complexity laboratories, mainly in developing countries. PMID:26273282

  2. Mycobacterium avium subsp. paratuberculosis as a trigger of type-1 diabetes: destination Sardinia, or beyond?

    PubMed Central

    2010-01-01

    Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease in which the insulin producing β cell population is destroyed by the infiltrated T lymphocytes. Even though the exact cause of T1DM is yet to be ascertained, varying degree of genetic susceptibility and environmental factors have been linked to the disease progress and outcome. Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate zoonotic pathogen that causes chronic infection of intestines in ruminants, the Johne's disease. MAP that can even survive pasteurization and chlorination has also been implicated to cause similar type of enteritis in humans called Crohn's disease. With the increasing recognition of the link between MAP and Crohn's disease, it has been postulated that MAP is an occult antigen which besides Crohn's could as well be thought to trigger T1DM. Epitope homologies between mycobacterial proteins (Hsp 65) and pancreatic glutamic acid decarboxylase (GAD 65) and infant nutrition studies implicate MAP as one of the triggers for T1DM. PCR and ELISA analyses in diabetic patients from Sardinia suggest that MAP acts as a possible trigger for T1DM. Systematic mechanistic insights are needed to prove this link. Unfortunately, no easy animal model(s) or in-vitro systems are available to decipher the complex immunological network that is triggered in MAP infection leading to T1DM. PMID:20350307

  3. Mycobacterium avium subsp. paratuberculosis as a trigger of type-1 diabetes: destination Sardinia, or beyond?

    PubMed

    Rani, Pittu Sandhya; Sechi, Leonardo A; Ahmed, Niyaz

    2010-03-29

    Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease in which the insulin producing beta cell population is destroyed by the infiltrated T lymphocytes. Even though the exact cause of T1DM is yet to be ascertained, varying degree of genetic susceptibility and environmental factors have been linked to the disease progress and outcome. Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate zoonotic pathogen that causes chronic infection of intestines in ruminants, the Johne's disease. MAP that can even survive pasteurization and chlorination has also been implicated to cause similar type of enteritis in humans called Crohn's disease. With the increasing recognition of the link between MAP and Crohn's disease, it has been postulated that MAP is an occult antigen which besides Crohn's could as well be thought to trigger T1DM. Epitope homologies between mycobacterial proteins (Hsp 65) and pancreatic glutamic acid decarboxylase (GAD 65) and infant nutrition studies implicate MAP as one of the triggers for T1DM. PCR and ELISA analyses in diabetic patients from Sardinia suggest that MAP acts as a possible trigger for T1DM. Systematic mechanistic insights are needed to prove this link. Unfortunately, no easy animal model(s) or in-vitro systems are available to decipher the complex immunological network that is triggered in MAP infection leading to T1DM.

  4. LAMP technology: Rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Trangoni, Marcos D; Gioffré, Andrea K; Cerón Cucchi, María E; Caimi, Karina C; Ruybal, Paula; Zumárraga, Martín J; Cravero, Silvio L

    2015-06-01

    In this study, we developed new sets of primers to detect Brucella spp. and M. avium subsp. paratuberculosis (MAP) through isothermal amplification. We selected a previously well-characterized target gene, bscp31, specific for Brucella spp. and IS900 for MAP. The limits of detection using the loop-mediated isothermal amplification (LAMP) protocols described herein were similar to those of conventional PCR targeting the same sequences. Hydroxynaphtol blue and SYBR Green(TM) allowed direct naked-eye detection with identical sensitivity as agarose gel electrophoresis. We included the LAMP-based protocol in a rapid identification scheme of the respective pathogens, and all tested isolates were correctly identified within 2 to 3 h. In addition, both protocols were suitable for specifically identifying the respective pathogens; in the case of Brucella, it also allowed the identification of all the biovars tested. We conclude that LAMP is a suitable rapid molecular typing tool that could help to shorten the time required to identify insidious bacteria in low-complexity laboratories, mainly in developing countries.

  5. Isolation, identification, and structural analysis of the mycobactins of Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum, and Mycobacterium paratuberculosis.

    PubMed Central

    Barclay, R; Ewing, D F; Ratledge, C

    1985-01-01

    Methods were devised to purify the cell-associated, iron-binding compounds known as mycobactins from the closely related species Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum (i.e., the MAIS complex of organisms). The mycobactins from these three species showed a structure that is common to the mycobactins from all the mycobacteria examined to date. However, these mycobactins were unique in that they had more than one alkyl chain. The M. scrofulaceum mycobactins differed from other MAIS mycobactins by a shift in the position of the double bond in the R1 alkyl chain. Traces of other mycobactin types were observed in ethanol extracts of the three species, and examination of the chromatographic properties of these mycobactins showed that each species produced five mycobactin types. Each mycobactin could be subdivided further by the length of its R1 alkyl chain. No differences in the production of these novel mycobactin were observed among species. Mycobactins from three strains of Mycobacterium paratuberculosis and two wood pigeon strains of Mycobacterium avium which had lost their original growth requirements for mycobactin after repeated subculturing in laboratory growth media were examined by thin-layer chromatography and high-pressure liquid chromatography. Each organism produced a mycobactin with similar chromatographic properties to those synthesized by MAIS organisms. M. paratuberculosis NADC 18 produced at least two components in our laboratory, and nuclear magnetic resonance analysis of the major component showed this mycobactin to be identical to that produced by M. intracellulare M12. However, a sample of mycobactin J isolated by Merkal and McCullough (Curr. Microbiol. 7:333-335, 1982) from M. paratuberculosis NADC 18 was different from our isolates and appeared to correspond to a minor mycobactin component we had seen by thin-layer chromatography. No reason for this difference could be evinced. Our findings indicate that

  6. Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides.

    PubMed

    Yasutake, Yoshiaki; Kusada, Hiroyuki; Ebuchi, Teppei; Hanada, Satoshi; Kamagata, Yoichi; Tamura, Tomohiro; Kimura, Nobutada

    2017-08-21

    Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhomoserine lactones (AHLs), a class of signalling compounds involved in quorum sensing, and β-lactam antibiotics. Thus, MacQ is crucial as a quencher of quorum sensing as well as in conferring antibiotic resistance in Acidovorax. Here, we report the X-ray structures of MacQ in ligand-free and reaction product complexes. MacQ forms a 170-kDa capsule-shaped molecule via face-to-face interaction with two heterodimers consisting of an α-chain and a β-chain, generated by the self-cleaving activity of a precursor polypeptide. The electron density of the spacer polypeptide in the hollow of the molecule revealed the close orientation of the peptide-bond atoms of Val20SP-Gly21SP to the active-site, implying a role of the residues in substrate binding. In mutational analyses, uncleaved MacQ retained degradation activity against both AHLs and penicillin G. These results provide novel insights into the mechanism of self-cleaving maturation and enzymatic function of N-terminal nucleophile hydrolases.

  7. Design and FPGA implementation for MAC layer of Ethernet PON

    NASA Astrophysics Data System (ADS)

    Zhu, Zengxi; Lin, Rujian; Chen, Jian; Ye, Jiajun; Chen, Xinqiao

    2004-04-01

    Ethernet passive optical network (EPON), which represents the convergence of low-cost, high-bandwidth and supporting multiple services, appears to be one of the best candidates for the next-generation access network. The work of standardizing EPON as a solution for access network is still underway in the IEEE802.3ah Ethernet in the first mile (EFM) task force. The final release is expected in 2004. Up to now, there has been no standard application specific integrated circuit (ASIC) chip available which fulfills the functions of media access control (MAC) layer of EPON. The MAC layer in EPON system has many functions, such as point-to-point emulation (P2PE), Ethernet MAC functionality, multi-point control protocol (MPCP), network operation, administration and maintenance (OAM) and link security. To implement those functions mentioned above, an embedded real-time operating system (RTOS) and a flexible programmable logic device (PLD) with an embedded processor are used. The software and hardware functions in MAC layer are realized through programming embedded microprocessor and field programmable gate array(FPGA). Finally, some experimental results are given in this paper. The method stated here can provide a valuable reference for developing EPON MAC layer ASIC.

  8. Survival of Mycobacterium avium in drinking water biofilms as affected by water flow velocity, availability of phosphorus, and temperature.

    PubMed

    Torvinen, Eila; Lehtola, Markku J; Martikainen, Pertti J; Miettinen, Ilkka T

    2007-10-01

    Mycobacterium avium is a potential pathogen occurring in drinking water systems. It is a slowly growing bacterium producing a thick cell wall containing mycolic acids, and it is known to resist chlorine better than many other microbes. Several studies have shown that pathogenic bacteria survive better in biofilms than in water. By using Propella biofilm reactors, we studied how factors generally influencing the growth of biofilms (flow rate, phosphorus concentration, and temperature) influence the survival of M. avium in drinking water biofilms. The growth of biofilms was followed by culture and DAPI (4',6'-diamidino-2-phenylindole) staining, and concentrations of M. avium were determined by culture and fluorescence in situ hybridization methods. The spiked M. avium survived in biofilms for the 4-week study period without a dramatic decline in concentration. The addition of phosphorus (10 microg/liter) increased the number of heterotrophic bacteria in biofilms but decreased the culturability of M. avium. The reason for this result is probably that phosphorus increased competition with other microbes. An increase in flow velocity had no effect on the survival of M. avium, although it increased the growth of biofilms. A higher temperature (20 degrees C versus 7 degrees C) increased both the number of heterotrophic bacteria and the survival of M. avium in biofilms. In conclusion, the results show that in terms of affecting the survival of slowly growing M. avium in biofilms, temperature is a more important factor than the availability of nutrients like phosphorus.

  9. ISOLATION OF THE GENOME SEQUENCE STRAIN MYCOBACTERIUM AVIUM 104 FROM MULTIPLE PATIENTS OVER A 17-YEAR PERIOD

    EPA Science Inventory

    The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated form an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genoty...

  10. ISOLATION OF THE GENOME SEQUENCE STRAIN MYCOBACTERIUM AVIUM 104 FROM MULTIPLE PATIENTS OVER A 17-YEAR PERIOD

    EPA Science Inventory

    The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated form an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genoty...

  11. The persistence of Mycobacterium avium in a drinking water system, what is the risk to human health?

    EPA Science Inventory

    Drinking water is believed to be a major source of human exposure to nontuberculous mycobacteria (NTM) such as Mycobacterium avium. We monitored the prevalence of M. avium in a drinking water system during the addition of filtration treatment. Our goal was to determine if the pre...

  12. Survival of Mycobacterium avium in Drinking Water Biofilms as Affected by Water Flow Velocity, Availability of Phosphorus, and Temperature▿

    PubMed Central

    Torvinen, Eila; Lehtola, Markku J.; Martikainen, Pertti J.; Miettinen, Ilkka T.

    2007-01-01

    Mycobacterium avium is a potential pathogen occurring in drinking water systems. It is a slowly growing bacterium producing a thick cell wall containing mycolic acids, and it is known to resist chlorine better than many other microbes. Several studies have shown that pathogenic bacteria survive better in biofilms than in water. By using Propella biofilm reactors, we studied how factors generally influencing the growth of biofilms (flow rate, phosphorus concentration, and temperature) influence the survival of M. avium in drinking water biofilms. The growth of biofilms was followed by culture and DAPI (4′,6′-diamidino-2-phenylindole) staining, and concentrations of M. avium were determined by culture and fluorescence in situ hybridization methods. The spiked M. avium survived in biofilms for the 4-week study period without a dramatic decline in concentration. The addition of phosphorus (10 μg/liter) increased the number of heterotrophic bacteria in biofilms but decreased the culturability of M. avium. The reason for this result is probably that phosphorus increased competition with other microbes. An increase in flow velocity had no effect on the survival of M. avium, although it increased the growth of biofilms. A higher temperature (20°C versus 7°C) increased both the number of heterotrophic bacteria and the survival of M. avium in biofilms. In conclusion, the results show that in terms of affecting the survival of slowly growing M. avium in biofilms, temperature is a more important factor than the availability of nutrients like phosphorus. PMID:17675427

  13. Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

    PubMed

    de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

    2011-03-01

    We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.

  14. Mycobacterium avium infections of Acanthamoeba strains: host strain variability, grazing-acquired infections, and altered dynamics of inactivation with monochloramine.

    PubMed

    Berry, David; Horn, Matthias; Xi, Chuanwu; Raskin, Lutgarde

    2010-10-01

    Stable Mycobacterium avium infections of several Acanthamoeba strains were characterized by increased infection resistance of recent environmental isolates and reduced infectivity in the presence of other bacteria. Exposure of M. avium in coculture with Acanthamoeba castellanii to monochloramine yielded inactivation kinetics markedly similar to those observed for A. castellanii alone.

  15. Rapid and sensitive method to identify Mycobacterium avium subsp. paratuberculosis in cow's milk by DNA methylase genotyping.

    PubMed

    Mundo, Silvia Leonor; Gilardoni, Liliana Rosa; Hoffman, Federico José; Lopez, Osvaldo Jorge

    2013-03-01

    Paratuberculosis is an infectious, chronic, and incurable disease that affects ruminants, caused by Mycobacterium avium subsp. paratuberculosis. This bacterium is shed primarily through feces of infected cows but can be also excreted in colostrum and milk and might survive pasteurization. Since an association of genomic sequences of M. avium subsp. paratuberculosis in patients with Crohn's disease has been described; it is of interest to rapidly detect M. avium subsp. paratuberculosis in milk for human consumption. IS900 insertion is used as a target for PCR amplification to identify the presence of M. avium subsp. paratuberculosis in biological samples. Two target sequences were selected: IS1 (155 bp) and IS2 (94 bp). These fragments have a 100% identity among all M. avium subsp. paratuberculosis strains sequenced. M. avium subsp. paratuberculosis was specifically concentrated from milk samples by immunomagnetic separation prior to performing PCR. The amplicons were characterized using DNA methylase Genotyping, i.e., the amplicons were methylated with 6-methyl-adenine and digested with restriction enzymes to confirm their identity. The methylated amplicons from 100 CFU of M. avium subsp. paratuberculosis can be visualized in a Western blot format using an anti-6-methyl-adenine monoclonal antibody. The use of DNA methyltransferase genotyping coupled to a scintillation proximity assay allows for the detection of up to 10 CFU of M. avium subsp. paratuberculosis per ml of milk. This test is rapid and sensitive and allows for automation and thus multiple samples can be tested at the same time.

  16. Rapid and Sensitive Method To Identify Mycobacterium avium subsp. paratuberculosis in Cow's Milk by DNA Methylase Genotyping

    PubMed Central

    Mundo, Silvia Leonor; Gilardoni, Liliana Rosa; Hoffman, Federico José

    2013-01-01

    Paratuberculosis is an infectious, chronic, and incurable disease that affects ruminants, caused by Mycobacterium avium subsp. paratuberculosis. This bacterium is shed primarily through feces of infected cows but can be also excreted in colostrum and milk and might survive pasteurization. Since an association of genomic sequences of M. avium subsp. paratuberculosis in patients with Crohn's disease has been described; it is of interest to rapidly detect M. avium subsp. paratuberculosis in milk for human consumption. IS900 insertion is used as a target for PCR amplification to identify the presence of M. avium subsp. paratuberculosis in biological samples. Two target sequences were selected: IS1 (155 bp) and IS2 (94 bp). These fragments have a 100% identity among all M. avium subsp. paratuberculosis strains sequenced. M. avium subsp. paratuberculosis was specifically concentrated from milk samples by immunomagnetic separation prior to performing PCR. The amplicons were characterized using DNA methylase Genotyping, i.e., the amplicons were methylated with 6-methyl-adenine and digested with restriction enzymes to confirm their identity. The methylated amplicons from 100 CFU of M. avium subsp. paratuberculosis can be visualized in a Western blot format using an anti-6-methyl-adenine monoclonal antibody. The use of DNA methyltransferase genotyping coupled to a scintillation proximity assay allows for the detection of up to 10 CFU of M. avium subsp. paratuberculosis per ml of milk. This test is rapid and sensitive and allows for automation and thus multiple samples can be tested at the same time. PMID:23275511

  17. The persistence of Mycobacterium avium in a drinking water system, what is the risk to human health?

    EPA Science Inventory

    Drinking water is believed to be a major source of human exposure to nontuberculous mycobacteria (NTM) such as Mycobacterium avium. We monitored the prevalence of M. avium in a drinking water system during the addition of filtration treatment. Our goal was to determine if the pre...

  18. Relationship between Presence of Cows with Milk Positive for Mycobacterium avium subsp. paratuberculosis-Specific Antibody by Enzyme-Linked Immunosorbent Assay and Viable M. avium subsp. paratuberculosis in Dust in Cattle Barns

    PubMed Central

    Chuchaisangrat, Ruj; Nielen, Mirjam; Koets, Ad P.

    2013-01-01

    Paratuberculosis, or Johne's disease, in cattle is caused by Mycobacterium avium subsp. paratuberculosis, which has recently been suspected to be transmitted through dust. This longitudinal study on eight commercial M. avium subsp. paratuberculosis-positive dairy farms studied the relationship between the number of cows with M. avium subsp. paratuberculosis antibody-positive milk and the presence of viable M. avium subsp. paratuberculosis in settled-dust samples, including their temporal relationship. Milk and dust samples were collected in parallel monthly for 2 years. M. avium subsp. paratuberculosis antibodies in milk were measured by enzyme-linked immunosorbent assay (ELISA) and used as a proxy for M. avium subsp. paratuberculosis shedding. Settled-dust samples were collected by using electrostatic dust collectors (EDCs) at six locations in housing for dairy cattle and young stock. The presence of viable M. avium subsp. paratuberculosis was identified by liquid culture and PCR. The results showed a positive relationship (odds ratio [OR], 1.2) between the number of cows with ELISA-positive milk and the odds of having positive EDCs in the same airspace as the adult dairy cattle. Moreover, the total number of lactating cows also showed an OR slightly above 1. This relationship remained the same for settled-dust samples collected up to 2 months before or after the time of milk sampling. The results suggest that removal of adult cows with milk positive for M. avium subsp. paratuberculosis-specific antibody by ELISA might result in a decrease in the presence of viable M. avium subsp. paratuberculosis in dust and therefore in the environment. However, this decrease is likely delayed by several weeks at least. In addition, the data support the notion that M. avium subsp. paratuberculosis exposure of young stock is reduced by separate housing. PMID:23793639

  19. Identification of Mycobacterium avium genes associated with resistance to host antimicrobial peptides

    PubMed Central

    Motamedi, Nima; Danelishvili, Lia

    2014-01-01

    Antimicrobial peptides are an important component of the innate immune defence. Mycobacterium avium subsp. hominissuis (M. avium) is an organism that establishes contact with the respiratory and gastrointestinal mucosa as a necessary step for infection. M. avium is resistant to high concentrations of polymyxin B, a surrogate for antimicrobial peptides. To determine gene-encoding proteins that are associated with this resistance, we screened a transposon library of M. avium strain 104 for susceptibility to polymyxin B. Ten susceptible mutants were identified and the inactivated genes sequenced. The great majority of the genes were related to cell wall synthesis and permeability. The mutants were then examined for their ability to enter macrophages and to survive macrophage killing. Three clones among the mutants had impaired uptake by macrophages compared with the WT strain, and all ten clones were attenuated in macrophages. The mutants were also shown to be susceptible to cathelicidin (LL-37), in contrast to the WT bacterium. All but one of the mutants were significantly attenuated in mice. In conclusion, this study indicated that the M. avium envelope is the primary defence against host antimicrobial peptides. PMID:24836414

  20. Induction and expression of protective T cells during Mycobacterium avium infections in mice.

    PubMed Central

    Appelberg, R; Pedrosa, J

    1992-01-01

    Mycobacterium avium is an opportunistic pathogen that infects individuals suffering from chronic lung disease or immunocompromised patients such as AIDS patients. Here we show that a highly virulent isolate of M. avium proliferated as extensively in T cell deficient as in immunocompetent mice. T cell deficient mice allowed a progressive growth of a less virulent AIDS-derived isolate of M. avium while immunocompetent mice arrested the growth of this isolate. Adoptive transfer of T cell enriched spleen cells between congenic strains of mice differing at the Bcg/Ity/Lsh locus showed that only naturally resistant BALB/c.Bcgr (C.D2) mice infected with the highly virulent strain of M. avium or the naturally susceptible BALB/c mice infected with the lower virulence isolate developed protective T cells and that these cells only mediated protection when transferred to naturally susceptible, but not to naturally resistant, mice. Both strains of M. avium proliferated in bone marrow-derived macrophages cultured in vitro and they were both susceptible to the bacteriostatic effects induced in the macrophages by crude lymphokines produced by concanavalin A-stimulated spleen cells. PMID:1544223

  1. Mycobacterium avium bacilli grow saprozoically in coculture with Acanthamoeba polyphaga and survive within cyst walls.

    PubMed

    Steinert, M; Birkness, K; White, E; Fields, B; Quinn, F

    1998-06-01

    Protozoans are gaining recognition as environmental hosts for a variety of waterborne pathogens. We compared the growth of Mycobacterium avium, a human pathogen associated with domestic water supplies, in coculture with the free-living amoeba Acanthamoeba polyphaga with the growth of M. avium when it was separated from amoebae by a 0.1-micron-pore-size polycarbonate membrane (in a parachamber). Although viable mycobacteria were observed within amoebal vacuoles, there was no significant difference between bacterial growth in coculture and bacterial growth in the parachamber. This suggests that M. avium is able to grow saprozoically on products secreted by the amoebae. In contrast, Legionella pneumophila, a well-studied intracellular parasite of amoebae, multiplied only in coculture. A comparison of amoebae infected with L. pneumophila and amoebae infected with M. avium by electron microscopy demonstrated that there were striking differences in the locations of the bacteria within amoebal cysts. While L. pneumophila resided within the cysts, M. avium was found within the outer walls of the double-walled cysts of A. polyphaga. These locations may provide a reservoir for the bacteria when environmental conditions become unfavorable.

  2. Estimation of Mycobacterium avium subsp. paratuberculosis growth parameters: strain characterization and comparison of methods.

    PubMed

    Elguezabal, Natalia; Bastida, Felix; Sevilla, Iker A; González, Nuria; Molina, Elena; Garrido, Joseba M; Juste, Ramón A

    2011-12-01

    The growth rate of Mycobacterium avium subsp. paratuberculosis was assessed by different methods in 7H9 medium supplemented with OADC (oleic acid, albumin, dextrose, catalase), Tween 80, and mycobactin J. Generation times and maximum specific growth rates were determined by wet weight, turbidometric measurement, viable count, and quantitative PCR (ParaTB-Kuanti; F57 gene) for 8 M. avium subsp. paratuberculosis strains (K10, 2E, 316F, 81, 445, 764, 22G, and OVICAP 49). Strain-to-strain differences were observed in growth curves and calculated parameters. The quantification methods gave different results for each strain at specific time points. Generation times ranged from an average of 1.4 days for viable count and qPCR to approximately 10 days for wet weight and turbidometry. The wet-weight, turbidometry, and ParaTB-Kuanti qPCR methods correlated best with each other. Generally, viability has been assessed by viable count as a reference method; however, due to M. avium subsp. paratuberculosis clumping problems and the presence of noncultivable M. avium subsp. paratuberculosis cells, we conclude that qPCR of a single-copy gene may be used reliably for rapid estimation of M. avium subsp. paratuberculosis bacterial numbers in a sample.

  3. Intracellular Mycobacterium avium Intersect Transferrin in the Rab11+ Recycling Endocytic Pathway and Avoid Lipocalin 2 Trafficking the Lysosomal Pathway

    PubMed Central

    Halaas, Øyvind; Steigedal, Magnus; Haug, Markus; Awuh, Jane A.; Ryan, Liv; Brech, Andreas; Sato, Shintaro; Husebye, Harald; Cangelosi, Gerard A.; Akira, Shizuo; Strong, Roland K.; Espevik, Terje; Flo, Trude H.

    2009-01-01

    Iron is an essential nutrient for microbes and many pathogenic bacteria depend on siderophores to obtain iron. The mammalian innate immunity protein lipocalin 2 (Lcn2, NGAL, 24p3, Siderocalin) binds the siderophore carboxymycobactin, an essential component of the iron acquisition apparatus of mycobacteria. Here we show that Lcn2 suppressed growth of Mycobacterium avium in culture, and M. avium induced Lcn2 production from mouse macrophages. Lcn2 was also elevated and initially limited the growth of M. avium in the blood of infected mice, but did not impede growth in tissues and during long-term infections. M. avium is an intracellular pathogen. Subcellular imaging of infected macrophages revealed that Lcn2 trafficked to lysosomes separate from M. avium, whereas transferrin was efficiently transported to the mycobacteria. Thus mycobacteria seem to reside in the Rab11+ endocytic recycling pathway, thereby retaining access to nutrition and avoiding endocytosed immunoproteins like Lcn2. PMID:20121435

  4. Immunoreactivity of protein tyrosine phosphatase A (PtpA) in sera from sheep infected with Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Gurung, Ratna B; Begg, Douglas J; Purdie, Auriol C; Bach, Horacio; Whittington, Richard J

    2014-07-15

    Evasion of host defense mechanisms and survival inside infected host macrophages are features of pathogenic mycobacteria including Mycobacterium avium subspecies paratuberculosis, the causative agent of Johne's disease in ruminants. Protein tyrosine phosphatase A (PtpA) has been identified as a secreted protein critical for survival of mycobacteria within infected macrophages. The host may mount an immune response to such secreted proteins. In this study, the humoral immune response to purified recombinant M. avium subsp. paratuberculosis PtpA was investigated using sera from a cohort of sheep infected with M. avium subsp. paratuberculosis and compared with uninfected healthy controls. A significantly higher level of reactivity to PtpA was observed in sera collected from M. avium subspecies paratuberculosis infected sheep when compared to those from uninfected healthy controls. PtpA could be a potential candidate antigen for detection of humoral immune responses in sheep infected with M. avium subspecies paratuberculosis.

  5. Dolphin natures, human virtues: MacIntyre and ethical naturalism.

    PubMed

    Glackin, Shane Nicholas

    2008-09-01

    Can biological facts explain human morality? Aristotelian 'virtue' ethics has traditionally assumed so. In recent years Alasdair MacIntyre has reintroduced a form of Aristotle's 'metaphysical biology' into his ethics. He argues that the ethological study of dependence and rationality in other species--dolphins in particular--sheds light on how those same traits in the typical lives of humans give rise to the moral virtues. However, some goal-oriented dolphin behaviour appears both dependent and rational in the precise manner which impresses MacIntyre, yet anything but ethically 'virtuous'. More damningly, dolphin ethologists consistently refuse to evaluate such behaviour in the manner MacIntyre claims is appropriate to moral judgement. In light of this, I argue that virtues--insofar as they name a biological or ethological category--do not name a morally significant one.

  6. Synthesizing Existing CSMA and TDMA Based MAC Protocols for VANETs.

    PubMed

    Huang, Jiawei; Li, Qi; Zhong, Shaohua; Liu, Lianhai; Zhong, Ping; Wang, Jianxin; Ye, Jin

    2017-02-10

    Many Carrier Sense Multiple Access (CSMA) and Time Division Multiple Access (TDMA) based medium access control (MAC) protocols for vehicular ad hoc networks (VANETs) have been proposed recently. Contrary to the common perception that they are competitors, we argue that the underlying strategies used in these MAC protocols are complementary. Based on this insight, we design CTMAC, a MAC protocol that synthesizes existing strategies; namely, random accessing channel (used in CSMA-style protocols) and arbitral reserving channel (used in TDMA-based protocols). CTMAC swiftly changes its strategy according to the vehicle density, and its performance is better than the state-of-the-art protocols. We evaluate CTMAC using at-scale simulations. Our results show that CTMAC reduces the channel completion time and increases the network goodput by 45% for a wide range of application workloads and network settings.

  7. Performance Analysis and Improvement of WPAN MAC for Home Networks

    PubMed Central

    Mehta, Saurabh; Kwak, Kyung Sup

    2010-01-01

    The wireless personal area network (WPAN) is an emerging wireless technology for future short range indoor and outdoor communication applications. The IEEE 802.15.3 medium access control (MAC) is proposed to coordinate the access to the wireless medium among the competing devices, especially for short range and high data rate applications in home networks. In this paper we use analytical modeling to study the performance analysis of WPAN (IEEE 802.15.3) MAC in terms of throughput, efficient bandwidth utilization, and delay with various ACK policies under error channel condition. This allows us to introduce a K-Dly-ACK-AGG policy, payload size adjustment mechanism, and Improved Backoff algorithm to improve the performance of the WPAN MAC. Performance evaluation results demonstrate the impact of our improvements on network capacity. Moreover, these results can be very useful to WPAN application designers and protocol architects to easily and correctly implement WPAN for home networking. PMID:22319274

  8. Performance analysis and improvement of WPAN MAC for home networks.

    PubMed

    Mehta, Saurabh; Kwak, Kyung Sup

    2010-01-01

    The wireless personal area network (WPAN) is an emerging wireless technology for future short range indoor and outdoor communication applications. The IEEE 802.15.3 medium access control (MAC) is proposed to coordinate the access to the wireless medium among the competing devices, especially for short range and high data rate applications in home networks. In this paper we use analytical modeling to study the performance analysis of WPAN (IEEE 802.15.3) MAC in terms of throughput, efficient bandwidth utilization, and delay with various ACK policies under error channel condition. This allows us to introduce a K-Dly-ACK-AGG policy, payload size adjustment mechanism, and Improved Backoff algorithm to improve the performance of the WPAN MAC. Performance evaluation results demonstrate the impact of our improvements on network capacity. Moreover, these results can be very useful to WPAN application designers and protocol architects to easily and correctly implement WPAN for home networking.

  9. Synthesizing Existing CSMA and TDMA Based MAC Protocols for VANETs

    PubMed Central

    Huang, Jiawei; Li, Qi; Zhong, Shaohua; Liu, Lianhai; Zhong, Ping; Wang, Jianxin; Ye, Jin

    2017-01-01

    Many Carrier Sense Multiple Access (CSMA) and Time Division Multiple Access (TDMA) based medium access control (MAC) protocols for vehicular ad hoc networks (VANETs) have been proposed recently. Contrary to the common perception that they are competitors, we argue that the underlying strategies used in these MAC protocols are complementary. Based on this insight, we design CTMAC, a MAC protocol that synthesizes existing strategies; namely, random accessing channel (used in CSMA-style protocols) and arbitral reserving channel (used in TDMA-based protocols). CTMAC swiftly changes its strategy according to the vehicle density, and its performance is better than the state-of-the-art protocols. We evaluate CTMAC using at-scale simulations. Our results show that CTMAC reduces the channel completion time and increases the network goodput by 45% for a wide range of application workloads and network settings. PMID:28208590

  10. SACRB-MAC: A High-Capacity MAC Protocol for Cognitive Radio Sensor Networks in Smart Grid

    PubMed Central

    Yang, Zhutian; Shi, Zhenguo; Jin, Chunlin

    2016-01-01

    The Cognitive Radio Sensor Network (CRSN) is considered as a viable solution to enhance various aspects of the electric power grid and to realize a smart grid. However, several challenges for CRSNs are generated due to the harsh wireless environment in a smart grid. As a result, throughput and reliability become critical issues. On the other hand, the spectrum aggregation technique is expected to play an important role in CRSNs in a smart grid. By using spectrum aggregation, the throughput of CRSNs can be improved efficiently, so as to address the unique challenges of CRSNs in a smart grid. In this regard, we proposed Spectrum Aggregation Cognitive Receiver-Based MAC (SACRB-MAC), which employs the spectrum aggregation technique to improve the throughput performance of CRSNs in a smart grid. Moreover, SACRB-MAC is a receiver-based MAC protocol, which can provide a good reliability performance. Analytical and simulation results demonstrate that SACRB-MAC is a promising solution for CRSNs in a smart grid. PMID:27043573

  11. SACRB-MAC: A High-Capacity MAC Protocol for Cognitive Radio Sensor Networks in Smart Grid.

    PubMed

    Yang, Zhutian; Shi, Zhenguo; Jin, Chunlin

    2016-03-31

    The Cognitive Radio Sensor Network (CRSN) is considered as a viable solution to enhance various aspects of the electric power grid and to realize a smart grid. However, several challenges for CRSNs are generated due to the harsh wireless environment in a smart grid. As a result, throughput and reliability become critical issues. On the other hand, the spectrum aggregation technique is expected to play an important role in CRSNs in a smart grid. By using spectrum aggregation, the throughput of CRSNs can be improved efficiently, so as to address the unique challenges of CRSNs in a smart grid. In this regard, we proposed Spectrum Aggregation Cognitive Receiver-Based MAC (SACRB-MAC), which employs the spectrum aggregation technique to improve the throughput performance of CRSNs in a smart grid. Moreover, SACRB-MAC is a receiver-based MAC protocol, which can provide a good reliability performance. Analytical and simulation results demonstrate that SACRB-MAC is a promising solution for CRSNs in a smart grid.

  12. A redescription of Lobatostoma kemostoma (MacCallum & MacCallum, 1913) (Trematoda: Aspidogastrea) from the florida pompano fish Trachinotus carolinus (Linnaeus, 1766) off the Brazilian coast.

    PubMed

    Alves, P V; Borges, J N; Santos, C P; Luque, J L

    2015-05-01

    A redescription of the aspidogastrean trematode Lobatostoma kemostoma (MacCallum & MacCallum, 1913) is provided based on examination of type material, voucher specimens available at institutional collections and newly collected specimens from the type host, Trachinotus carolinus (Linnaeus, 1766), off the Angra dos Reis, Brazil. Partial sequence of its 28S rDNA is given. Lobatostoma kemostoma can be distinguished from the other eight species of the genus by: (1) the hindbody being longer than the ventral disc; and (2) the cephalic lobes having the same shape and size. Features observed for the first time include the number and detailed arrangement of alveoli on the ventral disc, the terminal genitalia and the ovarian complex. New illustrations and morphometric data are given. In the present survey the host specificity in the genus, the validity of some morphological features and the occurrence of an Indian species of Lobatostoma from off the Brazilian coast are discussed. A lectotype of L. kemostoma from the type series deposited at United States National Parasite Collection is also designated.

  13. Vehicle Health Management Communications Requirements for AeroMACS

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Clements, Donna J.; Apaza, Rafael D.

    2012-01-01

    As the development of standards for the aeronautical mobile airport communications system (AeroMACS) progresses, the process of identifying and quantifying appropriate uses for the system is progressing. In addition to defining important elements of AeroMACS standards, indentifying the systems uses impacts AeroMACS bandwidth requirements. Although an initial 59 MHz spectrum allocation for AeroMACS was established in 2007, the allocation may be inadequate; studies have indicated that 100 MHz or more of spectrum may be required to support airport surface communications. Hence additional spectrum allocations have been proposed. Vehicle health management (VHM) systems, which can produce large volumes of vehicle health data, were not considered in the original bandwidth requirements analyses, and are therefore of interest in supporting proposals for additional AeroMACS spectrum. VHM systems are an emerging development in air vehicle safety, and preliminary estimates of the amount of data that will be produced and transmitted off an aircraft, both in flight and on the ground, have been prepared based on estimates of data produced by on-board vehicle health sensors and initial concepts of data processing approaches. This allowed an initial estimate of VHM data transmission requirements for the airport surface. More recently, vehicle-level systems designed to process and analyze VHM data and draw conclusions on the current state of vehicle health have been undergoing testing and evaluation. These systems make use of vehicle system data that is mostly different from VHM data considered previously for airport surface transmission, and produce processed system outputs that will be also need to be archived, thus generating additional data load for AeroMACS. This paper provides an analysis of airport surface data transmission requirements resulting from the vehicle level reasoning systems, within the context of overall VHM data requirements.

  14. AMPA receptor competitive antagonism reduces halothane MAC in rats.

    PubMed

    McFarlane, C; Warner, D S; Todd, M M; Nordholm, L

    1992-12-01

    Various subtypes of receptors have been identified for glutamate, an excitatory neurotransmitter. Previous studies have shown that antagonism of glutamate at the NMDA receptors reduces minimum alveolar concentration (MAC) for volatile anesthetics. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) is a selective antagonist at the glutamatergic AMPA receptor. The purpose of this experiment was to determine whether AMPA receptor antagonism influences halothane MAC in the rat. Sprague-Dawley rats were anesthetized with halothane in 50% O2/balance N2, tracheally intubated and the lungs were mechanically ventilated. Increasing doses of NBQX were intravenously infused in three groups while the control group was infused with vehicle (D5W). Halothane MAC was then determined by the tail-clamp method. Halothane MAC was log-linearly related to plasma NBQX concentrations (MAC = 0.125 (In plasma concentration NBQX) + 1.035, r2 = 0.77). A maximal 58% reduction of halothane MAC was achieved with an NBQX loading dose of 42 mg/kg followed by a continuous infusion rate of 36 mg x kg-1 x h-1 (control = 1.02 +/- 0.07%; NBQX = 0.43 +/- 0.12%; P < .01). Larger doses of NBQX were not possible because of the poor aqueous solubility of this compound. In a separate experiment, awake rats were randomly assigned to groups based on the dose of NBQX infused. Pa(CO2) and mean arterial pressure were measured at time 0 and at 5 and 30 min after start of NBQX infusion. The infusion was then stopped. Time until recovery of the righting reflex was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. A Flexible CSMA based MAC Protocol for Software Defined Radios

    NASA Astrophysics Data System (ADS)

    Puschmann, André; Kalil, Mohamed A.; Mitschele-Thiel, Andreas

    2012-09-01

    In this article, we propose a flexible CSMA based MAC protocol which facilitates research and experimentation using software define radios. The modular architecture allows to employ the protocol on platforms with heterogeneous hardware capabilities and provides the freedom to exchange or adapt the spectrum sensing mechanism without modifying the MAC protocol internals. We discuss the architecture of the protocol and provide structural details of its main components. Furthermore, we present throughput measurements that have been obtained on an example system using host-based spectrum sensing.

  16. Detecting local establishment strategies of wild cherry (Prunus avium L.).

    PubMed

    Höltken, Aki M; Gregorius, Hans-Rolf

    2006-10-04

    P. avium, a pioneer tree species that colonizes early forest successional stages, is assumed to require an effective strategy allowing stably repeatable rounds of local establishment, dispersal and local extinction. Consequently, the early replacement of cherry by climax tree species makes the establishment of several local generations very unlikely, especially in central European continuous cover forests. This has to be seen in connection with the mixed reproduction system involving asexual reproduction as a complementary adaptational strategy. Tests of the local establishment of wild cherry must therefore consider the possibility of first generation establishment via seedling recruitment potentially followed by an asexual generation (root suckering). Successful establishment can therefore be determined only among adult individuals with the option of detecting vegetative reproduction at these stages. To test the implied suggestion about local establishment strategies of wild cherry, nuclear microsatellites were used to analyse patterns of asexual propagation among adult stages that have been subjected to one of two major types of forest management. These management types, the historical "coppice with standards system" (CWS) and the "high forest system" (HFS), can be reasonably assumed to have affected the reproduction system of P. avium. Clear differences were found in the reproduction pattern between two stands representing the two forest management types: 1) Clonal propagation is observed in both management systems, but with a distinctly higher frequency in the CWS. Hence, sexual recruitment as a first local generation is followed by a second asexual generation in both, whereas in the CWS there is evidence for an additional clonal generation. 2) The estimation of amounts of clonal reproduction critically depends on the assumptions about multilocus gene associations. This is revealed by the application of newly developed methods of quantifying gene associations

  17. Detecting local establishment strategies of wild cherry (Prunus avium L.)

    PubMed Central

    Höltken, Aki M; Gregorius, Hans-Rolf

    2006-01-01

    Backround P. avium, a pioneer tree species that colonizes early forest successional stages, is assumed to require an effective strategy allowing stably repeatable rounds of local establishment, dispersal and local extinction. Consequently, the early replacement of cherry by climax tree species makes the establishment of several local generations very unlikely, especially in central European continuous cover forests. This has to be seen in connection with the mixed reproduction system involving asexual reproduction as a complementary adaptational strategy. Tests of the local establishment of wild cherry must therefore consider the possibility of first generation establishment via seedling recruitment potentially followed by an asexual generation (root suckering). Successful establishment can therefore be determined only among adult individuals with the option of detecting vegetative reproduction at these stages. To test the implied suggestion about local establishment strategies of wild cherry, nuclear microsatellites were used to analyse patterns of asexual propagation among adult stages that have been subjected to one of two major types of forest management. These management types, the historical "coppice with standards system" (CWS) and the "high forest system" (HFS), can be reasonably assumed to have affected the reproduction system of P. avium. Results Clear differences were found in the reproduction pattern between two stands representing the two forest management types: 1) Clonal propagation is observed in both management systems, but with a distinctly higher frequency in the CWS. Hence, sexual recruitment as a first local generation is followed by a second asexual generation in both, whereas in the CWS there is evidence for an additional clonal generation. 2) The estimation of amounts of clonal reproduction critically depends on the assumptions about multilocus gene associations. This is revealed by the application of newly developed methods of quantifying

  18. Virulence and molecular aspects of Bordetella avium isolated from cockatiel chicks (Nymphicus hollandicus) in Brazil.

    PubMed

    Grespan, A; Camera, O; Knöbl, T; Gomes, C R; Felizardo, M R; Ferreira, T S P; Gobbi, D D S; Moreno, M; Sanches, A A; Ferreira, C S A; Ferreira, A J P; Moreno, A M

    2012-12-07

    Bordetella avium is an opportunistic pathogen that presents tropism for ciliated epithelia, leading to upper respiratory tract disease in turkeys. This agent has also been associated with Lockjaw Syndrome in psittacine birds, but literatures describing the importance of this agent in such species are rare. The purpose of the present study was to report the first outbreak of B. avium infection in juvenile cockatiels demonstrating the Lockjaw Syndrome in Brazil and to investigate the antimicrobial resistance profile and phenotypic and genotypic characteristics of these strains. Surprising, the strains obtained from five infected cockatiel chicks from three different breeders from different Brazilian states showed a clonal relationship using the Pulsed Field Gel Electrophoresis and Single Enzyme Amplified Fragment Length Polymorphism techniques. The virulence potentials of the B. avium strains were assessed using tracheal adherence and cytotoxic effects on a VERO cell monolayer. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Pathogenesis of systemic Mycobacterium avium infection in pigs through histological analysis of hepatic lesions

    PubMed Central

    Hibiya, Kenji; Utsunomiya, Kimiko; Yoshida, Takashi; Toma, Satoshi; Higa, Futoshi; Tateyama, Masao; Fujita, Jiro

    2010-01-01

    Mycobacterium avium causes systemic infections through primary intestinal lesions in pigs. However, its pathogenesis is not well understood. The aim of this study was to confirm the effects on swine after enteral infection. One hundred and twelve pigs with hepatic lesions infected with M. avium were used in this study. We investigated the involvement of other organs and the distribution of hepatic lesions in the lobular structure. Most lesions involved the mesenteric lymph nodes. Hepatic lymph nodes were the secondary nodes involved. In 74 cases (66.1%), the hepatic lesions were predominantly distributed in the portal tract of the affected livers. The other 38 cases (33.9%) showed granulomatous lesions in the hepatic lobule. Many cases showed interface hepatitis. There was a significant relationship between focal lesions within hepatic lobule and splenic lesions. These findings suggest that granulomatous lesions formed in hepatic lobules upon establishment of bacteremia in pigs systemically infected with M. avium. PMID:21197224

  20. Disseminated mycobacteriosis due to Mycobacterium avium in captive Bengal tiger (Panthera tigris).

    PubMed

    Cho, Ho-Seong; Kim, Yong-Hwan; Park, Nam-Yong

    2006-05-01

    A 2-year-old captive female Bengal Tiger (Panthera tigris) died after prolonged anorexia in the Gwangju Uchi Park Zoo, Gwangju, Republic of Korea. Necropsy revealed multiple nodules of varying sizes in the lung, liver, kidney, and spleen. Histopathologic examination revealed a typical granuloma composed of caseous necrotic areas surrounded by lymphocytes with a few giant cells and foamy macrophages. Periodic acid-Schiff stain and Gomori methenamine silver stain did not reveal any fungal bodies. The Ziehl-Neelsen acid-fast stain revealed few acid-fast organisms in the lung, liver, kidney, and spleen. A polymerase chain reaction assay of the lung, liver, kidney, and spleen yielded a positive result for Mycobacterium avium subsp. avium. This is an unusual case of disseminated infection of a wild mammal with avian mycobacteriosis, and is believed to be most likely associated with the feeding of tigers with culled chickens infected with M. avium.

  1. Tracheal mucus transport rate in normal turkeys and in turkeys infected with Bordetella avium (Alcaligenes faecalis).

    PubMed

    Ficken, M D; Edwards, J F; Lay, J C; Tveter, D E

    1986-01-01

    Using the radiopharmaceutical 99mtechnetium-sulfur colloid, the tracheal mucus transport rate (TMTR) was measured in healthy unanesthetized turkeys and in turkeys infected with Bordetella avium. The TMTR of uninfected turkeys was 35.6 +/- 14.4 cm/min. The TMTR of B. avium-infected turkeys was normal on days 0 through 14 postexposure (PE), despite heavy bacterial colonization of the tracheal epithelium. On day 21 PE, the TMTR of B. avium-infected turkeys was significantly depressed (P less than or equal to 0.01) compared with that of control turkeys. Depressed transport was associated with extensive loss of ciliated epithelium from the tracheal mucosa and replacement of the normal mucosa by immature nonciliated epithelium or metaplastic squamous epithelium.

  2. Complexity.

    PubMed

    Gómez-Hernández, J Jaime

    2006-01-01

    It is difficult to define complexity in modeling. Complexity is often associated with uncertainty since modeling uncertainty is an intrinsically difficult task. However, modeling uncertainty does not require, necessarily, complex models, in the sense of a model requiring an unmanageable number of degrees of freedom to characterize the aquifer. The relationship between complexity, uncertainty, heterogeneity, and stochastic modeling is not simple. Aquifer models should be able to quantify the uncertainty of their predictions, which can be done using stochastic models that produce heterogeneous realizations of aquifer parameters. This is the type of complexity addressed in this article.

  3. Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection.

    PubMed Central

    Oh, Y K; Nix, D E; Straubinger, R M

    1995-01-01

    Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial system. Current therapy is not highly effective. Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more efficiently to M. avium-infected cells. We investigated the formulation of the antibiotics ciprofloxacin and azithromycin in liposomes and tested their antibacterial activities in vitro against M. avium residing within J774, a murine macrophage-like cell line. A conventional passive-entrapment method yielded an encapsulation efficiency of 9% for ciprofloxacin and because of aggregation mediated by the cationic drug, was useful only with liposomes containing < or = 50 mol% negatively charged phospholipid. In contrast, ciprofloxacin was encapsulated with > 90% efficiency, regardless of the content of negatively charged lipids, by a remote-loading technique that utilized both pH and potential gradients to drive drug into preformed liposomes. Both the cellular accumulation and the antimycobacterial activity of ciprofloxacin increased in proportion to the liposome negative charge; the maximal enhancement of potency was 43-fold in liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5). Azithromycin liposomes were prepared as a freeze-dried preparation to avoid chemical instability during storage, and drug could be incorporated at 33 mol% (with respect to phospholipid). Azithromycin also showed enhanced antimycobacterial effect in liposomes, and the potency increased in parallel to the moles percent of negatively charged lipids; azithromycin in DSPG-Chol (10:5) liposomes inhibited intracellular M. avium growth 41-fold more effectively than did free azithromycin. Thus, ciprofloxacin or azithromycin encapsulated in stable liposomes having substantial negative surface charge is superior to nonencapsulated drug in inhibition of M.avium growth within cultured

  4. Immunoreactivity of the Mycobacterium avium subsp. paratuberculosis 19-kDa lipoprotein

    PubMed Central

    Huntley, Jason FJ; Stabel, Judith R; Bannantine, John P

    2005-01-01

    Background The Mycobacterium tuberculosis 19-kDa lipoprotein has been reported to stimulate both T and B cell responses as well as induce a number of Th1 cytokines. In order to evaluate the Mycobacterium avium subsp. paratuberculosis (M. avium subsp. paratuberculosis) 19-kDa lipoprotein as an immunomodulator in cattle with Johne's disease, the gene encoding the 19-kDa protein (MAP0261c) was analyzed. Results MAP0261c is conserved in mycobacteria, showing a 95% amino acid identity in M. avium subspecies avium, 84% in M. intracellulare and 76% in M. bovis and M. tuberculosis. MAP0261c was cloned, expressed, and purified as a fusion protein with the maltose-binding protein (MBP-19 kDa) in Escherichia coli. IFN-γ production was measured from 21 naturally infected and 9 control cattle after peripheral blood mononuclear cells (PBMCs) were stimulated with a whole cell lysate (WCL) of M. avium subsp. paratuberculosis or the recombinant MBP-19 kDa. Overall, the mean response to MBP-19 kDa was not as strong as the mean response to the WCL. By comparison, cells from control, non-infected cattle did not produce IFN-γ after stimulation with either WCL or MBP-19 kDa. To assess the humoral immune response to the 19-kDa protein, sera from cattle with clinical Johne's disease were used in immunoblot analysis. Reactivity to MBP-19 kDa protein, but not MBP alone, was observed in 9 of 14 infected cattle. Antibodies to the 19-kDa protein were not observed in 8 of 9 control cows. Conclusions Collectively, these results demonstrate that while the 19-kDa protein from M. avium subsp. paratuberculosis stimulates a humoral immune response and weak IFN-γ production in infected cattle, the elicited responses are not strong enough to be used in a sensitive diagnostic assay. PMID:15663791

  5. IgG protease Mac/IdeS is not essential for phagocyte resistance or mouse virulence of M1T1 group A Streptococcus.

    PubMed

    Okumura, Cheryl Y M; Anderson, Ericka L; Döhrmann, Simon; Tran, Dan N; Olson, Joshua; von Pawel-Rammingen, Ulrich; Nizet, Victor

    2013-07-30

    The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds. Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly

  6. Mycobacterium avium subsp. paratuberculosis: pathogen, pathogenesis and diagnosis.

    PubMed

    Manning, E J; Collins, M T

    2001-04-01

    Johne's disease, or paratuberculosis, is a chronic intestinal infection caused by Mycobacterium avium subsp. paratuberculosis. The usually fatal disease is characterised by cachexia, and in some species diarrhoea, after a long pre-clinical phase. Treatment is ineffective and economically impracticable. The infection primarily affects domestic and free-ranging ruminants, but has also been reported in primates, rabbits, stoats and foxes. Since paratuberculosis is often subclinical, under-reporting is suspected, even though the disease is notifiable in numerous countries. Herd prevalence of bovine paratuberculosis in Europe ranges from 7% to 55%. In the United States of America, herd prevalence is strongly associated with herd size; 40% of herds of more than 300 head were found to be infected. In Australia, reported dairy herd infection rates range between 9% and 22%. Paratuberculosis in domestic livestock entails significant economic losses due to several factors (e.g. reduced production, premature culling and increased veterinary costs). Free-ranging and captive wildlife are also at risk from paratuberculosis.

  7. Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development

    PubMed Central

    Ni, Zhiyou; Lin, Lijin; Tang, Yi; Wang, Zhihui; Wang, Xun; Wang, Jin; Lv, Xiulan; Xia, Hui

    2017-01-01

    To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium ‘Hongdeng’), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit. PMID:28245268

  8. Peptides specific for Mycobacterium avium subspecies paratuberculosis infection: diagnostic potential.

    PubMed

    Casey, J L; Sanalla, A M; Tamvakis, D; Thalmann, C; Carroll, E L; Parisi, K; Coley, A M; Stewart, D J; Vaughan, J A; Michalski, W P; Luke, R; Foley, M

    2011-08-01

    Mycobacterium avium subspecies paratuberculosis (Map) is the causative agent of Johne's disease (JD). Current serological diagnostic tests for JD are limited by their sensitivity when used in sub-clinical stages of the disease. Our objective was to identify peptides that mimic diagnostically important Map epitopes that might be incorporated into a new-generation JD diagnostic. Four peptides were isolated from a phage-displayed random peptide library by screening on antibodies derived from Map-infected goats. The peptides were recognised by antibodies from Map-infected goats but not by antibodies from uninfected goats. The peptides elicited immune responses in rabbits, which reacted strongly with bona fide Map antigens proving the peptides were true epitope mimics. To assess the diagnostic value a panel of goat sera was screened for reactivity's with peptides. The peptides were recognised by antibodies from a proportion of goats infected with Map compared with control animals with a diagnostic specificity of 100% and the sensitivity ranged from 50 to 75%. Combinations of any two peptides improved sensitivity 62.5-87.5% and 100% sensitivity was achieved with three of the four peptides in combination. These data suggest peptides representing diagnostically important Map epitopes could be incorporated into a sensitive diagnostic test.

  9. Identification of immunoreactive proteins of Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Piras, Cristian; Soggiu, Alessio; Bonizzi, Luigi; Greco, Viviana; Ricchi, Matteo; Arrigoni, Norma; Bassols, Anna; Urbani, Andrea; Roncada, Paola

    2015-02-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the cause of a chronic enteritis of ruminants (bovine paratuberculosis (PTB)--Johne's disease) that is associated with enormous worldwide economic losses for the animal production. Diagnosis is based on observation of clinical signs, the detection of antibodies in milk or serum, or evaluation of bacterial culture from feces. The limit of these methods is that they are not able to detect the disease in the subclinical stage and are applicable only when the disease is already advanced. For this reason, the main purpose of this study is to use the MAP proteome to detect novel immunoreactive proteins that may be helpful for PTB diagnoses. 2DE and 2D immunoblotting of MAP proteins were performed using sera of control cattle and PTB-infected cattle in order to highlight the specific immunoreactive proteins. Among the assigned identifiers to immunoreactive spots it was found that most of them correspond to surface-located proteins while three of them have never been described before as antigens. The identification of these proteins improves scientific knowledge that could be useful for PTB diagnoses. The sequence of the identified protein can be used for the synthesis of immunoreactive peptides that could be screened for their immunoreaction against bovine sera infected with MAP. All MS data have been deposited in the ProteomeXchange consortium with identifier PXD001159 and DOI 10.6019/PXD001159.

  10. Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection

    PubMed Central

    2016-01-01

    Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized. PMID:27489800

  11. Control of Mycobacterium avium subsp. paratuberculosis infection in agricultural species.

    PubMed

    Kennedy, D J; Benedictus, G

    2001-04-01

    Paratuberculosis or Johne's disease is a chronic intestinal disease caused by Mycobacterium avium subsp. paratuberculosis, which continues to spread in agricultural species. Control of paratuberculosis is challenging and should not be underestimated. Due to the long incubation period of the infection, disease is largely subclinical in domesticated livestock. Hence, direct effects on animal productivity and welfare are often masked and may appear insufficient to justify large investments in control programmes by individual farmers, livestock industries or governments. Furthermore, in some countries the main effects of the disease are indirect, resulting from the impact of market discrimination against herds and flocks known to be infected, or from the control measures enforced to reduce transmission. In such circumstances, producers may be unwilling to co-operate with surveillance that may detect infection in herds or flocks. As control programmes are rarely successful in eliminating the infection from a herd or flock in the short term without an aggressive and costly programme, financial and community support assists producers to deal with the challenge. Successful prevention and control depends on animal health authorities and livestock industries acquiring a good understanding of the nature and epidemiology of infection, and of the application of tools for diagnosis and control. Building support for control programmes under the leadership of the affected livestock industries is critical, as programmes are unlikely to be successful without ongoing political will, supported by funding for research, surveillance and control.

  12. Mycobacterium avium paratuberculosis in wild boars in Korea.

    PubMed

    Kim, Jae-Myung; Ku, Bok Kyung; Lee, Haet-nim; Hwang, In-Yeong; Jang, Young-Boo; Kim, Jaejo; Hyun, Bang-Hun; Jung, Suk Chan

    2013-04-01

    Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic infectious enteritis in various domestic and wild mammals and is widely distributed globally. Interspecies transmission has been frequently reported. We investigated the presence of MAP from December 2010 to March 2011 in blood and feces collected from 222 hunter-killed wild boars. We collected 197 serum and 180 fecal samples and examined them by culture, PCR, and enzyme-linked immunosorbent assay. We investigated the status of MAP infection and the MAP genotypes in the wild boar population of Korea by using IS900 PCR and IS1311-restriction endonuclease analysis typing. Of the 180 fecal samples cultured, MAP colonies were recovered from two. By PCR, 18 animals were positive for MAP and one serum sample had a strong humoral response to MAP. The PCR-positive DNA samples from the colonies and the feces samples were genotyped as "cattle type" and "bison type," which are major MAP genotypes infecting domestic species in Korea. Our study provides new information on mycobacterial infection among wild boars, and suggests that a more effective program should be developed to monitor mycobacterial infections in wild animal populations in Korea.

  13. Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development.

    PubMed

    Liang, Dong; Zhu, Tingting; Ni, Zhiyou; Lin, Lijin; Tang, Yi; Wang, Zhihui; Wang, Xun; Wang, Jin; Lv, Xiulan; Xia, Hui

    2017-01-01

    To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium 'Hongdeng'), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit.

  14. Simulation and Analysis of a Wireless Mac Protocol: MACAW.

    DTIC Science & Technology

    1996-09-01

    MACAW (Medium Access Collision Avoidance Wireless) is a new MAC protocol for wireless LANs proposed by Bharghavan et al. Ref. 2 based on Karn’s MACA...performance of the MACAW protocol occurs at approximately 50% channel load. We have also shown the importance of the backoff algorithm, and finally, we have

  15. Activation of human neutrophil Mac-1 by anion substitution *

    PubMed Central

    Lomakina, Elena; Knauf, Philip A.; Schultz, Joanne B.; Law, Foon-Yee; McGraw, Matthew D.; Waugh, Richard E.

    2009-01-01

    Substituting the medium chloride with glucuronate or glutamate causes a rapid, 10 to 30 –fold, increase in the binding of the monoclonal antibody, CBRM1/5, which recognizes the high-affinity conformation of the Mac-1 integrin. This change is reflected in functional adhesion assays that show increased adhesion to ICAM-1 coated beads. Blocking antibodies indicate that the increased adhesion is almost entirely d