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Volume 59, Issue 1

Identification of virulence determinants of that impact on the ability to resist host killing mechanisms Free

Abstract

is an opportunistic pathogen associated with pulmonary disease in non-AIDS patients and disseminated infection in patients with AIDS. The chief route of infection is by colonization and invasion of the mucosa of the gastrointestinal tract, but infection through the respiratory route also occurs. After crossing the mucosa, infects and replicates within tissue macrophages. To identify genes required for survival , a library of signature-tagged transposon mutants was constructed and screened for clones attenuated in mice. Thirty-two clones were found to be attenuated for their virulence, from which eleven were sequenced and tested further. All the mutants studied grew similarly to the wild-type MAC104. Ten mutants were tested individually in mice, confirming the attenuated phenotype. MAV_2450, a polyketide synthase homologue to pks12, was identified. STM5 and STM10 genes (encoding two hypothetical proteins MAV_4292 and MAV_4012) were associated with susceptibility to oxidative products. Mutants MAV_2450, MAV_4292, MAV_0385 and MAV_4264 live in macrophage vacuoles with acidic pH (below 6.9). Mutants MAV_4292, MAV_0385 and MAV_4264 were susceptible to nitric oxide . The study of individual mutants can potentially lead to new knowledge about pathogenic mechanisms.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): IFN-γ, gamma interferon , ROI, reactive oxygen intermediate , SOD, superoxide dismutase , STM, signature-tagged mutagenesis and WT, wild-type
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2010-01-01
2024-04-19
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Identification of virulence determinants of Mycobacterium avium that impact on the ability to resist host killing mechanisms
J. Med. Microbiol. 59, 8 (2010); https://doi.org/10.1099/jmm.0.012864-0
/content/journal/jmm/10.1099/jmm.0.012864-0
/content/journal/jmm/10.1099/jmm.0.012864-0
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