Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis.
The Mycobacterium tuberculosis genome encodes 12 alternative sigma factors, several of which regulate stress responses and are required for virulence in animal models of acute infection. In this work we investigated M. tuberculosis SigM, a member of the extracytoplasmic function subfamily of alternative sigma factors. This sigma factor is expressed at low levels in vitro and does not appear to function in stress response regulation. Instead, SigM positively regulates genes required for the synthesis of surface or secreted molecules. Among these are genes encoding two pairs of Esx secreted proteins, a multisubunit nonribosomal peptide synthetase operon, and genes encoding two members of the proline-proline-glutamate (PPE) family of proteins. Genes up regulated in a sigM mutant strain include a different PPE gene, as well as several genes involved in surface lipid synthesis. Among these are genes involved in synthesis of phthiocerol dimycocerosate (PDIM), a surface lipid critical for virulence during acute infection, and the kasA-kasB operon, which is required for mycolic acid synthesis. Analysis of surface lipids showed that PDIM synthesis is increased in a sigM-disrupted strain and is undetectable in a sigM overexpression strain. These findings demonstrate that SigM positively and negatively regulates cell surface and secreted molecules that are likely to function in host-pathogen interactions.
Raman
Sahadevan
S
Division of Infectious Diseases, Children's Hospital, Boston, MA 02115, USA.
Puyang
Xiaoling
X
Cheng
Tan-Yun
TY
Young
David C
DC
Moody
D Branch
DB
Husson
Robert N
RN
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D009171:Mycolic Acids / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D008055:Lipids; D009171:Mycolic Acids; D012808:Sigma Factor; C008901:phthiocerol dimycocerosate; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase