Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis.
Two-component systems are important constituents of bacterial regulatory networks. Results of this investigation into the role of the MprAB two-component system of Mycobacterium tuberculosis indicate that it is associated with the regulation of several stress-responsive regulons. Using a deletion mutant lacking portions of the response regulator, MprA, and the histidine kinase, MprB, it was demonstrated by real-time PCR, primer extension analyses and DNA microarrays that MprAB activates sigma factor genes sigE and sigB, under SDS stress and during exponential growth. SDS-inducible, MprA-dependent transcriptional start points were identified for mprA, sigE and sigB, and variations in distance between these points and MprA-binding sites suggest that MprA is involved in different mechanisms of promoter activation. Although most of the SigE regulon was downregulated in the deletion mutant, the cluster of genes Rv1129c, Rv1130 and Rv1131, which is associated with growth in monocytes, was upregulated in the deletion mutant under SDS stress, and this upregulation was dependent upon atmospheric growth conditions. Multiple stress-associated genes of the DosR, SigD and IdeR regulons were also upregulated in the deletion mutant, during exponential growth and/or in the presence of SDS. Surprisingly, the deletion mutant had increased resistance to SDS compared to the parental strain, and enhanced growth in human peripheral blood monocytes, characteristics which may result from a loss of repression of stress-associated genes.
Pang
Xiuhua
X
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Vu
Phong
P
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Byrd
Thomas F
TF
Department of Medicine, Albuquerque Veterans Affairs Medical Center, 1501 San Pedro SE, Albuquerque, NM 87108, USA.
Ghanny
Saleena
S
Center for Applied Genomics, Public Health Research Institute, 225 Warren St, Newark, NJ 07103, USA.
Soteropoulos
Patricia
P
Center for Applied Genomics, Public Health Research Institute, 225 Warren St, Newark, NJ 07103, USA.
Mukamolova
Galina V
GV
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Wu
Shiping
S
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Samten
Buka
B
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Howard
Susan T
ST
Department of Microbiology and Immunology, Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018085:Regulon; D012808:Sigma Factor / Q000235:genetics
D001426:Bacterial Proteins; C480224:MprA protein, Mycobacterium tuberculosis; C079011:SigB protein, Bacteria; D012808:Sigma Factor; C111259:sigE protein, Bacteria; D011494:Protein Kinases; C480223:MprB protein, Mycobacterium tuberculosis