A non‐RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis

JA MacGurn, S Raghavan, SA Stanley… - Molecular …, 2005 - Wiley Online Library
JA MacGurn, S Raghavan, SA Stanley, JS Cox
Molecular microbiology, 2005Wiley Online Library
The Snm secretion system is a crucial virulence determinant of Mycobacterium tuberculosis.
Genes encoding all known components of this alternative secretion pathway are clustered at
the same genetic locus, known as RD1. Here, we show that a mutant M. tuberculosis strain
containing a transposon insertion in the Rv3615c gene, which is situated outside the RD1
locus, results in loss of Snm secretion. Complementation analysis revealed that both
Rv3615c and the downstream gene Rv3614c are required for Snm secretion. Thus, we have …
Summary
The Snm secretion system is a crucial virulence determinant of Mycobacterium tuberculosis. Genes encoding all known components of this alternative secretion pathway are clustered at the same genetic locus, known as RD1. Here, we show that a mutant M. tuberculosis strain containing a transposon insertion in the Rv3615c gene, which is situated outside the RD1 locus, results in loss of Snm secretion. Complementation analysis revealed that both Rv3615c and the downstream gene Rv3614c are required for Snm secretion. Thus, we have renamed the two genes snm9 and snm10 respectively. The snm9::Tn mutant phenocopies bona fide snm mutants, exhibiting attenuation in mice, macrophage growth defects and failure to suppress cytokine induction. Furthermore, yeast two‐hybrid analysis revealed a physical interaction between Snm10 and Snm7 (Rv3882c), suggesting that Snm10 may function in complex with other Snm proteins during secretion. Thus, snm9 and snm10 are the first genes located outside the RD1 locus identified as critical components of Snm secretion. These data indicate that Snm secretion consists of an elaborate network of interactions that likely arose from multiple  duplication  events  during  the  evolution  of M.  tuberculosis.
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