The Mycobacterium tuberculosis ECF sigma factor sigma(E): role in global gene expression and survival in macrophages

In previously published work, we identified three Mycobacterium tuberculosi s sigma (sigma) factor genes responding to heat shock (sigB, sigrE and sigH ). Two of them (sigB and sigE) also responded to SDS exposure. As these res ponses to stress suggested that the cr factors encoded by these genes could be involved in pathogenicity, we are studying their role in physiology and virulence. In this work, we characterize a sigE mutant of M. tuberculosis H37Rv. The sigE mutant strain was more sensitive than the wild-type strain to heat shock, SDS and various oxidative stresses. It was also defective in the ability to grow inside both human and murine unactivated macrophages a nd was more sensitive than the wild-type strain to the killing activity of activated murine macrophages. Using microarray technology and quantitative reverse transcription - polymerase chain reaction (RT-PCR), we started to d efine the sigma (E) regulon of M. tuberculosis and its involvement in the g lobal regulation of the stress induced by SDS. We showed the requirement fo r a functional sigE gene for full expression of sigB and for its induction after SDS exposure but not after heat shock. We also identified several gen es that are no longer induced when sigma (E) is absent. These genes encode proteins belonging to different classes including transcriptional regulator s, enzymes involved in fatty acid degradation and classical heat shock prot eins.