Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6

TD Bold, DC Davis, KK Penberthy, LM Cox, JD Ernst, BC de Jong

Research output: Contribution to journalA1: Web of Science-article

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
JournalJournal of Infectious Diseases
Volume205
Issue number6
Pages (from-to)984-990
ISSN0022-1899
DOIs
Publication statusPublished - 2012

Keywords

  • B780-tropical-medicine
  • Bacterial diseases
  • Tuberculosis
  • Mycobacterium africanum
  • Mycobacterium tuberculosis complex
  • Mycobacterium tuberculosis
  • Infectivity
  • Comparison
  • Disease progression
  • Mutations
  • In vitro
  • In vivo
  • Growth
  • Kinetics
  • T-cells
  • Antigen detection
  • Gambia
  • Africa-West

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