Epidemiologic consequences of microvariation in mycobacterium tuberculosis

Mathema, Barun, Kurepina, Natalia, Yang, Guibin, Shashkina, Elena, Manca, Claudia, Mehaffy, Carolina, Bielefeldt-Ohmann, Helle, Ahuja, Shama, Fallows, Dorothy A., Izzo, Angelo, Bifani, Pablo, Dobos, Karen, Kaplan, Gilla and Kreiswirth, Barry N. (2012) Epidemiologic consequences of microvariation in mycobacterium tuberculosis. Journal of Infectious Diseases, 205 6: 964-974. doi:10.1093/infdis/jir876

Author Mathema, Barun
Kurepina, Natalia
Yang, Guibin
Shashkina, Elena
Manca, Claudia
Mehaffy, Carolina
Bielefeldt-Ohmann, Helle
Ahuja, Shama
Fallows, Dorothy A.
Izzo, Angelo
Bifani, Pablo
Dobos, Karen
Kaplan, Gilla
Kreiswirth, Barry N.
Title Epidemiologic consequences of microvariation in mycobacterium tuberculosis
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
Publication date 2012-03-01
Sub-type Article (original research)
DOI 10.1093/infdis/jir876
Open Access Status DOI
Volume 205
Issue 6
Start page 964
End page 974
Total pages 11
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Formatted abstract
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.

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.

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.

Natural variation, with detectable phenotypic changes, among closely related clinical isolates of M. tuberculosis may alter epidemiologic patterns in human populations.
Keyword New-York-City
Direct Repeat Locus
Molecular Epidemiology
Human Monocytes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: 7 February 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Veterinary Science Publications
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