1887

Abstract

Pathogenic strains of mycobacteria produce copious amounts of glutamine synthetase (GS) in the culture medium. The enzyme activity is linked to synthesis of poly-α--glutamine (PLG) in the cell walls. This study describes a mutant of that produces reduced levels of GS. The mutant was able to grow in enriched 7H9 medium without glutamine supplementation. The strain contained no detectable PLG in the cell walls and showed marked sensitivity to different chemical and physical stresses such as lysozyme, SDS and sonication. The sensitivity of the mutant to two antitubercular drugs, rifampicin and -cycloserine, was also increased. The strain infected THP-1 cells with reduced efficiency and was also attenuated for growth in macrophages. A strain containing the gene survived longer in THP-1 cells than the wild-type strain and also produced cell wall-associated PLG. The mutant was not able to replicate in the organs of BALB/c mice and was cleared within 4–6 weeks of infection. Disruption of the gene adversely affected biofilm formation on polystyrene surfaces. The results of this study demonstrate that the absence of not only attenuates the pathogen but also affects cell surface properties by altering the cell wall chemistry of the organism via the synthesis of PLG; this may be a target for drug development.

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2010-12-01
2020-04-04
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