Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6.
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.
Department of Medicine, New York University School of Medicine, New York, NY, USA.
Tyler D
TD
Bold
Daphne C
DC
Davis
Kristen K
KK
Penberthy
Laura M
LM
Cox
Joel D
JD
Ernst
Bouke C
BC
de Jong
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005816:Genetic Complementation Test; D056084:Genetic Fitness; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009161:Mycobacterium / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D037521:Virulence Factors; C527546:rv3879c antigen, Mycobacterium tuberculosis