| Epidemiologic consequences of microvariation in Mycobacterium tuberculosis. | |
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MedLine Citation:
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PMID: 22315279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Evidence from genotype-phenotype studies suggests that genetic diversity in pathogens have clinically relevant manifestations that can impact outcome of infection and epidemiologic success. We studied 5 closely related Mycobacterium tuberculosis strains that collectively caused extensive disease (n = 862), particularly among US-born tuberculosis patients. METHODS: Representative isolates were selected using population-based genotyping data from New York City and New Jersey. Growth and cytokine/chemokine response were measured in infected human monocytes. Survival was determined in aerosol-infected guinea pigs. RESULTS: Multiple genotyping methods and phylogenetically informative synonymous single nucleotide polymorphisms showed that all strains were related by descent. In axenic culture, all strains grew similarly. However, infection of monocytes revealed 2 growth phenotypes, slower (doubling ∼55 hours) and faster (∼25 hours). The faster growing strains elicited more tumor necrosis factor α and interleukin 1β than the slower growing strains, even after heat killing, and caused accelerated death of infected guinea pigs (∼9 weeks vs 24 weeks) associated with increased lung inflammation/pathology. Epidemiologically, the faster growing strains were associated with human immunodeficiency virus and more limited in spread, possibly related to their inherent ability to induce a strong protective innate immune response in immune competent hosts. CONCLUSIONS: Natural variation, with detectable phenotypic changes, among closely related clinical isolates of M. tuberculosis may alter epidemiologic patterns in human populations. |
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Authors:
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Barun Mathema; Natalia Kurepina; Guibin Yang; Elena Shashkina; Claudia Manca; Carolina Mehaffy; Helle Bielefeldt-Ohmann; Shama Ahuja; Dorothy A Fallows; Angelo Izzo; Pablo Bifani; Karen Dobos; Gilla Kaplan; Barry N Kreiswirth |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2012-02-07 |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 205 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-21 Completed Date: 2012-04-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 964-74 Citation Subset: AIM; IM |
Affiliation:
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Public Health Research Institute, Newark, NJ, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Axenic Culture Cytokines / metabolism Evolution, Molecular Female Genetic Variation* Genotype Guinea Pigs Humans Immunity, Innate Leukocytes, Mononuclear / metabolism Middle Aged Mycobacterium tuberculosis / classification, genetics*, isolation & purification* New Jersey / epidemiology New York City / epidemiology Phenotype Polymorphism, Single Nucleotide Prevalence Tuberculosis / epidemiology*, microbiology |
| Grant Support | |
ID/Acronym/Agency:
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R01AI066046/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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