1. Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6.
- Author
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Bold TD, Davis DC, Penberthy KK, Cox LM, Ernst JD, and de Jong BC
- Subjects
- Animals, Antigens, Bacterial genetics, Antigens, Bacterial immunology, Bacterial Proteins genetics, Bacterial Proteins immunology, Genetic Complementation Test, Genetic Fitness, Humans, Male, Mice, Mice, Inbred C57BL, Mutation, Mycobacterium pathogenicity, Mycobacterium tuberculosis pathogenicity, T-Lymphocytes immunology, Virulence Factors genetics, Bacterial Proteins metabolism, Mycobacterium genetics, Mycobacterium immunology, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis immunology
- 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.
- Published
- 2012
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