The Mycobacterium tuberculosis ECF sigma factor sE: role in global gene expression and survival in macrophages ±

Riccardo Manganelli1,2, Martin I. Voskuil3, Gary K. Schoolnik3, and Issar Smith1

1TB Center, The Public Health Research Institute, 455 First Avenue, New York, NY 10016, USA.   2Sezione di Microbiologia, Dipartimento di Istologia, Microbiologia e Biotecnologie Mediche, Università di Padova, 35121 Padova, Italy.   3Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract: In previously published work, we identified three M. tuberculosis sigma (s) factor genes responding to heat shock (sigB, sigE and sigH). Two of them (sigB and sigE) also responded to SDS exposure. As these responses to stress suggested that the s 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 and was more sensitive than the wild type strain to the killing activity of activated murine macrophages. Using microarray technology and quantitative RT-PCR we started to define the sE regulon of M. tuberculosis and its involvement in the global regulation of the stress induced by SDS. We showed the requirement of 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 genes that are no longer induced when sE is absent. These genes encode proteins belonging to different classes including transcriptional regulators, enzymes involved in fatty acid degradation and classical heat shock proteins.