1887

Abstract

The potential pathogenic role of H37Rv , a gene encoding an acyl-CoA synthase that is underexpressed in the attenuated strain H37Ra, was investigated. In a first approach, was cloned and expressed in strain H37Ra to restore gene expression and -complemented bacteria were used to investigate whether might confer any growth advantage to H37Ra in an infection model of BALB/c mice. No differences were found in the growth rates of H37Rv, H37Ra and -complemented H37Ra in the lungs and spleen. In contrast, in the liver, where the attenuated strain H37Ra showed impaired growth compared to the virulent strain H37Rv, complementation of the attenuated strain H37Ra with restored bacterial replication. In a further approach, the gene of strain H37Rv was disrupted by allelic exchange mutagenesis and the virulence of the mutant strain was tested by mouse infection. It was found that disruption of decreased H37Rv growth in the liver, but not in the lungs or spleen, and complementation of the -disrupted mutant with restored bacterial replication in the liver, but did not affect replication in the lungs and spleen. These findings suggest that plays a role in virulence by supporting bacterial growth in the liver.

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2002-12-01
2019-12-13
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