Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6

Tyler D. Bold, Daphne C. Davis, Kristen K. Penberthy, Laura M. Cox, Joel D. Ernst, Bouke C. De Jong

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22 Scopus citations

Abstract

Background. When compared with Mycobacterium tuberculosis, individuals that live in the same household as an active case of smear-positive pulmonary tuberculosis exposed to M. africanum progress less frequently to active disease within 2 years. A putative ESX-1 secretion apparatus member, Rv3879c, is mutated in M. africanum, and individuals infected with M. africanum less frequently demonstrate T-cell responses to the ESX-1-secreted virulence factor ESAT-6 than those infected with M. tuberculosis. We hypothesized that less frequent progression is caused by impaired secretion of ESAT-6. Methods. We analyzed in vivo growth and in vitro secretion of ESAT-6 and CFP-10, comparing M. tuberculosis to M. africanum and a strain of M. africanum complemented with M. tuberculosis Rv3879c. Results. ESAT-6 and CFP-10 secretion were similar for all strains, although these were enriched in M. africanum cell lysates, suggesting a modest ESX-1 secretion defect unrelated to the Rv3879c mutation. In mice, M. africanum demonstrated smaller bacterial population sizes than M. tuberculosis but similar numbers and frequencies of ESAT-6-responsive T cells in the lungs. Conclusions. These results confirm impaired fitness of M. africanum in vivo and indicate that Rv3879c is not required for secretion of ESAT-6 or for its presentation as an antigen to T cells in vivo.

Original languageEnglish (US)
Pages (from-to)984-990
Number of pages7
JournalJournal of Infectious Diseases
Volume205
Issue number6
DOIs
StatePublished - Mar 15 2012
Externally publishedYes

Bibliographical note

Funding Information:
Financial support. This work was supported in part by grants from the National Institutes of Health (R01 AI051242, R01 AI084041, and R01 AI090928 to J. D. E; 5K01 TW006083-06 to B. C. D. J.; and F30 HL096342 to T. D. B.) and the American Lung Association (RG-167675 to B. C. D. J.). Potential conflicts of interest. All authors: No reported conflicts.

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