Database : MEDLINE
Search on : mycobacterium and infections [Words]
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[PMID]: 29506484
[Au] Autor:van de Loo K; Balzer S; MacKenzie CR; Boemers TM; Ortmann M; Schaper J; Borkhardt A; Laws HJ; Kuhlen M
[Ad] Address:Department of Paediatric Oncology, Medical Faculty, Haematology and Clinical Immunology, Centre for Child and Adolescent Health, University of Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany. Karoline.vandeLoo@med.uni-duesseldorf.de.
[Ti] Title:Lymphnode tuberculosis in a 4-year-old boy with relapsed ganglioneuroblastoma: a case report.
[So] Source:BMC Infect Dis;18(1):105, 2018 Mar 05.
[Is] ISSN:1471-2334
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Mycobacterium tuberculosis (M. tuberculosis) disease is a generally well-known problem among immunocompromised adults and children. In pediatric oncology, only few cases of M. tuberculosis disease are reported so far. CASE PRESENTATION: We report a case of concomitant lymphnode tuberculosis in a 4-year-old German boy with relapsed ganglioneuroblastoma. 18 months after the initial diagnosis, relapse with new paravertebral lesions and new lesions in the left lower lobe of the lung and in the perihilar lymphnodes suspicious of metastases of the ganglioneuroblastoma were detected. While relapse in the tumor was confirmed, unexpectedly, pathologic examination revealed morphological diagnosis of lymphnode tuberculosis. The boy was of German background without previous history of tuberculosis exposure. Both, antituberculostatic and relapse treatment were immediately initiated. Three months on, MRI revealed regressive findings in the lung and lymphnodes and partial response in the tumor. The patient underwent second MiBG therapy and haploidentical stem cell transplantation. CONCLUSION: The diagnosis of lymphnode tuberculosis in a 4-year-old German boy with relapsed ganglioneuroblastoma was only made by chance, but most likely saved his life. Pediatric oncologist should be aware of tuberculosis as the incidence might increase over time and the timely diagnosis of a potentially preventable M. tuberculosis disease is irreplaceable. Further studies are needed to explore the incidence of M. tuberculosis infections and the value of IGRA, testing for latent tuberculosis infection prior to chemotherapy in children with underlying malignancies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1186/s12879-018-3016-x

  2 / 65634 MEDLINE  
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[PMID]: 29484749
[Au] Autor:Khosravi AD; Meghdadi H; Ghadiri AA; Alami A; Sina AH; Mirsaeidi M
[Ad] Address:Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
[Ti] Title:rpoB gene mutations among Mycobacterium tuberculosis isolates from extrapulmonary sites.
[So] Source:APMIS;126(3):241-247, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] Country of publication:Denmark
[La] Language:eng
[Ab] Abstract:The aim of this study was to analyze mutations occurring in the rpoB gene of Mycobacterium tuberculosis (MTB) isolates from clinical samples of extrapulmonary tuberculosis (EPTB). Seventy formalin-fixed, paraffin-embedded samples and fresh tissue samples from confirmed EPTB cases were analyzed. Nested PCR based on the rpoB gene was performed on the extracted DNAs, combined with cloning and subsequent sequencing. Sixty-seven (95.7%) samples were positive for nester PCR. Sequence analysis of the 81 bp region of the rpoB gene demonstrated mutations in 41 (61.2%) of 67 sequenced samples. Several point mutations including deletion mutations at codons 510, 512, 513 and 515, with 45% and 51% of the mutations in codons 512 and 513 respectively were seen, along with 26% replacement mutations at codons 509, 513, 514, 518, 520, 524 and 531. The most common alteration was Gln → His, at codon 513, presented in 30 (75.6%) isolates. This study demonstrated sequence alterations in codon 513 of the 81 bp region of the rpoB gene as the most common mutation occurred in 75.6% of molecularly confirmed rifampin-resistant strains. In addition, simultaneous mutation at codons 512 and 513 was demonstrated in 34.3% of the isolates.
[Mh] MeSH terms primary: Antibiotics, Antitubercular/pharmacology
Bacterial Proteins/genetics
DNA-Directed RNA Polymerases/genetics
Drug Resistance, Bacterial/genetics
Mycobacterium tuberculosis/genetics
Rifampin/pharmacology
Tuberculosis/microbiology
[Mh] MeSH terms secundary: Adult
Aged
Aged, 80 and over
Cells, Cultured
Female
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Mycobacterium tuberculosis/drug effects
Mycobacterium tuberculosis/isolation & purification
Point Mutation/genetics
Sequence Deletion/genetics
Young Adult
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antibiotics, Antitubercular); 0 (Bacterial Proteins); 0 (rpoB protein, Mycobacterium tuberculosis); EC 2.7.7.6 (DNA-Directed RNA Polymerases); VJT6J7R4TR (Rifampin)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180228
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12804

  3 / 65634 MEDLINE  
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[PMID]: 29401501
[Au] Autor:Inomata T; Konno S; Nagai K; Suzuki M; Nishimura M
[Ad] Address:First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
[Ti] Title:Neutrophil predominance in bronchoalveolar lavage fluid is associated with disease severity and progression of HRCT findings in pulmonary Mycobacterium avium infection.
[So] Source:PLoS One;13(2):e0190189, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pulmonary Mycobacterium avium complex (MAC) infection is increasing in prevalence worldwide even in immunocompetent individuals. Despite its variable clinical course, the clinical and immunological factors associated with radiographical severity and progression are not largely unknown. We aimed to study the association between the inflammatory cell and cytokine profiles at the local infected site, and the radiological severity and/or progression of pulmonary MAC infection. In this retrospective cohort study, 22 healthy subjects and 37 consecutive patients who were diagnosed as having pulmonary MAC infection by positive cultures of bronchoalveolar lavage (BAL) fluids were enrolled. The 37 patients were divided into 2 groups based on the predominant BAL inflammatory cell type: the lymphocyte-dominant (LD) group and neutrophil-dominant (ND) groups. The high-resolution computed tomography score in both the lavaged segment and whole lung and cytokines profiles were compared between the 2 groups. The clinical course after the BAL procedure was also compared between the 2 groups. Both the segment and whole lung scores in the ND group were significantly higher than the LD group (P < 0.001). Levels of IL-8 in the BAL fluids were significantly higher in the ND group compared to the LD group (P = 0.01). In contrast, levels of IL-22 were significantly lower in the ND group compared to the LD group (P < 0.001). The prevalence of patients who showed deterioration of the disease was significantly higher in the ND group (83.3%) than the LD group (12.5%) (P < 0.01). Neutrophil-predominant inflammatory response at the infected site is associated with the radiographical severity and progression of pulmonary MAC infection.
[Mh] MeSH terms primary: Bronchoalveolar Lavage Fluid/immunology
Mycobacterium avium-intracellulare Infection/immunology
Neutrophils/immunology
Tomography, X-Ray Computed/methods
[Mh] MeSH terms secundary: Adult
Aged
Case-Control Studies
Chemokines/metabolism
Cytokines/metabolism
Disease Progression
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Middle Aged
Mycobacterium avium-intracellulare Infection/diagnostic imaging
Mycobacterium avium-intracellulare Infection/pathology
Severity of Illness Index
Young Adult
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Chemokines); 0 (Cytokines)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190189

  4 / 65634 MEDLINE  
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[PMID]: 29385208
[Au] Autor:Mupfumi L; Moyo S; Molebatsi K; Thami PK; Anderson M; Mogashoa T; Iketleng T; Makhema J; Marlink R; Kasvosve I; Essex M; Musonda RM; Gaseitsiwe S
[Ad] Address:Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
[Ti] Title:Immunological non-response and low hemoglobin levels are predictors of incident tuberculosis among HIV-infected individuals on Truvada-based therapy in Botswana.
[So] Source:PLoS One;13(1):e0192030, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: There is a high burden of tuberculosis (TB) in HIV antiretroviral programmes in Africa. However, few studies have looked at predictors of incident TB while on Truvada-based combination antiretroviral therapy (cART) regimens. METHODS: We estimated TB incidence among individuals enrolled into an observational cohort evaluating the efficacy and tolerability of Truvada-based cART in Gaborone, Botswana between 2008 and 2011. We used Cox proportional hazards regressions to determine predictors of incident TB. RESULTS: Of 300 participants enrolled, 45 (15%) had a diagnosis of TB at baseline. During 428 person-years (py) of follow-up, the incidence rate of TB was 3.04/100py (95% CI, 1.69-5.06), with 60% of the cases occurring within 3 months of ART initiation. Incident cases had low baseline CD4+ T cell counts (153cells/mm3 [Q1, Q3: 82, 242]; p = 0.69) and hemoglobin levels (9.2g/dl [Q1, Q3: 8.5,10.1]; p<0.01). In univariate analysis, low BMI (HR = 0.73; 95% CI 0.58-0.91; p = 0.01) and hemoglobin levels <8 g/dl (HR = 10.84; 95%CI: 2.99-40.06; p<0.01) were risk factors for TB. Time to incident TB diagnosis was significantly reduced in patients with poor immunological recovery (p = 0.04). There was no association between baseline viral load and risk of TB (HR = 1.75; 95%CI: 0.70-4.37). CONCLUSION: Low hemoglobin levels prior to initiation of ART are significant predictors of incident tuberculosis. Therefore, there is potential utility of iron biomarkers to identify patients at risk of TB prior to initiation on ART. Furthermore, additional strategies are required for patients with poor immunological recovery to reduce excess risk of TB while on ART.
[Mh] MeSH terms primary: HIV Infections/complications
Hemoglobins/metabolism
Tuberculosis/complications
[Mh] MeSH terms secundary: Adult
Botswana
CD4 Lymphocyte Count
Female
HIV Infections/blood
HIV Infections/immunology
Humans
Male
Retrospective Studies
Risk Factors
Tuberculosis/blood
Tuberculosis/diagnosis
Tuberculosis/immunology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Hemoglobins)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192030

  5 / 65634 MEDLINE  
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[PMID]: 29364960
[Au] Autor:McCarthy K; Fielding K; Churchyard GJ; Grant AD
[Ad] Address:The Aurum Institute; Johannesburg, South Africa.
[Ti] Title:Empiric tuberculosis treatment in South African primary health care facilities - for whom, where, when and why: Implications for the development of tuberculosis diagnostic tests.
[So] Source:PLoS One;13(1):e0191608, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: The extent and circumstances under which empiric tuberculosis (TB) treatment (treatment without microbiological confirmation at treatment initiation) is administered in primary health care settings in South Africa are not well described. METHODS: We used data from a pragmatic evaluation of Xpert MTB/RIF in which persons undergoing TB investigations by PHC nurses were followed for six months. Following Xpert or smear-microscopy at enrolment, investigations for tuberculosis were undertaken at the discretion of health care workers. We identified persons whose TB treatment was initiated empirically (no microbiological confirmation at time of treatment initiation at a primary health care facility) and describe pathways to treatment initiation. RESULTS: Of 4665 evaluable participants, 541 persons were initiated on treatment of whom 167 (31%) had negative sputum tests at enrolment. Amongst these 167, the median number of participant visits to health care providers prior to treatment initiation was 3 (interquartile range [IQR] 2-4). Chest radiography, sputum culture or hospital referral was done in 106/167 (63%). Reasons for TB treatment start were: 1) empiric (n = 82, 49%); 2) a positive laboratory test (n = 49, 29%); 3) referral and treatment start at a higher level of care (n = 28, 17%); and 4) indeterminable (n = 8, 5%). Empiric treatment accounted for 15% (82/541) of all TB treatment initiations and 1.7% (82/4665) of all persons undergoing TB investigations. Chest radiography findings compatible with TB (63/82 [77%]) were the basis for treatment initiation amongst the majority of empirically treated participants. Microbiological confirmation of TB was subsequently obtained for 11/82 (13%) empirically-treated participants. Median time to empiric treatment start was 3.9 weeks (IQR 1.4-11 weeks) after enrolment. CONCLUSION: Uncommon prescription of empiric TB treatment with reliance on chest radiography in a nurse-managed programme underscores the need for highly sensitive TB diagnostics suitable for point-of-care, and strong health systems to support TB diagnosis in this setting.
[Mh] MeSH terms primary: Antitubercular Agents/therapeutic use
Primary Health Care
Tuberculosis/drug therapy
[Mh] MeSH terms secundary: Adult
Female
Humans
Male
Middle Aged
South Africa
Tuberculosis/diagnosis
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antitubercular Agents)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191608

  6 / 65634 MEDLINE  
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[PMID]: 29324800
[Au] Autor:Harrington-Kandt R; Stylianou E; Eddowes LA; Lim PJ; Stockdale L; Pinpathomrat N; Bull N; Pasricha J; Ulaszewska M; Beglov Y; Vaulont S; Drakesmith H; McShane H
[Ad] Address:Jenner Institute, University of Oxford, Oxford, United Kingdom.
[Ti] Title:Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model.
[So] Source:PLoS One;13(1):e0191038, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines.
[Mh] MeSH terms primary: Anemia, Iron-Deficiency/complications
Disease Models, Animal
Disease Susceptibility
Hepcidins/deficiency
Mycobacterium tuberculosis/pathogenicity
Tuberculosis/pathology
[Mh] MeSH terms secundary: Animals
Female
Hepcidins/genetics
Homeostasis
Iron/metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Tuberculosis/complications
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Hepcidins); E1UOL152H7 (Iron)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191038

  7 / 65634 MEDLINE  
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[PMID]: 29241819
[Au] Autor:Nguyen PC; Madani A; Santucci P; Martin BP; Paudel RR; Delattre S; Herrmann JL; Spilling CD; Kremer L; Canaan S; Cavalier JF
[Ad] Address:Aix-Marseille Univ., CNRS, LISM, IMMFR3479, Marseille, France.
[Ti] Title:Cyclophostin and Cyclipostins analogues, new promising molecules to treat mycobacterial-related diseases.
[So] Source:Int J Antimicrob Agents;, 2017 Dec 11.
[Is] ISSN:1872-7913
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The progression of mycobacterial diseases requires the development of new therapeutics. This study evaluated the efficacy and selectivity of a panel of Cyclophostin and Cyclipostins analogues (CyCs) against various bacteria and mycobacteria. The activity 26 CyCs was first assayed by the agar plate method. Compounds exhibiting 50-100% growth inhibition were then selected to determine their minimum inhibitory concentrations (MICs) by the resazurin microtiter assay (REMA). The best drug candidate was further tested against clinical mycobacterial isolates and bacteria responsible for nosocomial infections, including 6 Gram-negative bacteria, 5 Gram-positive bacteria, 29 rapid-growing mycobacteria belonging to the Mycobacterium chelonae-abscessus clade and 3 slow-growing mycobacteria (Mycobacterium marinum, Mycobacterium bovis BCG and Mycobacterium tuberculosis). Among the 26 CyCs tested, 10 were active and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate (CyC ) was further tested against 26 clinical strains and showed high selectivity for mycobacteria, with MICs (<2-40 µg/mL) comparable with those of most classical antimicrobials used to treat M. abscessus infections. Together, these results support the fact that such CyCs represent a new family of potent and selective inhibitors against mycobacteria. This is of particular interest for future chemotherapeutic developments against mycobacterial-associated infections, especially against M. abscessus, the most drug-resistant mycobacterial species.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 65634 MEDLINE  
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[PMID]: 29480804
[Au] Autor:Boyaci H; Chen J; Lilic M; Palka M; Mooney RA; Landick R; Darst SA; Campbell EA
[Ad] Address:The Rockefeller University, New York, United States.
[Ti] Title:Fidaxomicin jams RNA polymerase motions needed for initiation via RbpA contacts.
[So] Source:Elife;7, 2018 Feb 26.
[Is] ISSN:2050-084X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against RNAP in vitro, but clinical use of Fdx is limited to treating intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 Å cryo-electron microscopy structure of a complete RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on . Additional structures define conformational states of RNAP between the free apo-holoenzyme and the promoter-engaged open complex ready for transcription. The results establish that Fdx acts like a doorstop to jam the enzyme in an open state, preventing the motions necessary to secure promoter DNA in the active site. Our results provide a structural platform to guide development of anti-tuberculosis antimicrobials based on the Fdx binding pocket.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review

  9 / 65634 MEDLINE  
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[PMID]: 29458544
[Au] Autor:Aguilar-Ayala DA; Cnockaert M; Vandamme P; Palomino JC; Martin A; Gonzalez-Y-Merchand J
[Ad] Address:2​Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
[Ti] Title:Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions.
[So] Source:J Med Microbiol;67(3):282-285, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
[Mh] MeSH terms primary: Anti-Bacterial Agents/pharmacology
Lipids/pharmacology
Mycobacterium tuberculosis/drug effects
Mycobacterium tuberculosis/physiology
[Mh] MeSH terms secundary: Amikacin/pharmacology
Antitubercular Agents/pharmacology
Drug Tolerance
Fluoroquinolones/pharmacology
Genetic Fitness
Genotype
Humans
Lipid Metabolism
Microbial Sensitivity Tests
Models, Biological
Mycobacterium Infections, Nontuberculous/microbiology
Mycobacterium tuberculosis/genetics
Mycobacterium tuberculosis/growth & development
Nitroimidazoles/pharmacology
Rifampin/pharmacology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Anti-Bacterial Agents); 0 (Antitubercular Agents); 0 (Fluoroquinolones); 0 (Lipids); 0 (Nitroimidazoles); 84319SGC3C (Amikacin); U188XYD42P (moxifloxacin); VJT6J7R4TR (Rifampin)
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000681

  10 / 65634 MEDLINE  
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[PMID]: 29263106
[Au] Autor:Monin L; Mehta S; Elsegeiny W; Gopal R; McAleer JP; Oury TD; Kolls J; Khader SA
[Ad] Address:Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA.
[Ti] Title:Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.
[So] Source:Infect Immun;86(3), 2018 Mar.
[Is] ISSN:1098-5522
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with We established a new mouse model to investigate the relationship between and pulmonary infections. In this model, animals exposed to and coinfected with exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with alone. This increased control of infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in control in -coinfected lungs. Our results demonstrate that , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact control in a mouse model.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review


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