Identification of a novel gene product that promotes survival of Mycobacterium smegmatis in macrophages.

PloS One
Assunta PelosiRoss L Coppel

Abstract

Bacteria of the suborder Corynebacterineae include significant human pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in mycobacteria is increasingly common making identification of new antimicrobials a priority. Mycobacteria replicate intracellularly, most commonly within the phagosomes of macrophages, and bacterial proteins essential for intracellular survival and persistence are particularly attractive targets for intervention with new generations of anti-mycobacterial drugs. We have identified a novel gene that, when inactivated, leads to accelerated death of M. smegmatis within a macrophage cell line in the first eight hours following infection. Complementation of the mutant with an intact copy of the gene restored survival to near wild type levels. Gene disruption did not affect growth compared to wild type M. smegmatis in axenic culture or in the presence of low pH or reactive oxygen intermediates, suggesting the growth defect is not related to increased susceptibility to these stresses. The disrupted gene, MSMEG_5817, is conserved in all mycobacteria for which genome sequence information is available, and designated Rv0807 in M. tuberculosis. Although homology searches suggest that MSMEG_5817 ...Continue Reading

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Citations

Sep 10, 2014·Acta Crystallographica. Section D, Biological Crystallography·Adam ShahineTravis Beddoe
May 23, 2013·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Adam E ShahineTravis Beddoe
Oct 27, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Qinqin HuangJianping Xie
Jun 13, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Zhen GongJianping Xie

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Methods Mentioned

BETA
PCR
targeted knockout
FACS
FCS

Software Mentioned

ExPASy ( Expert Protein Analysis System )
BLASTP
CXP

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