TABLE 5.

Mycobacterial growth regulatory systems

Growth regulatory system(s)MechanismMycobacterial protein(s)Function
STPKsSensors of environmental signals that regulate host-pathogen interactions and developmental changes through signal transduction using reversible phosphorylation of proteins; M. tuberculosis encodes 12 STPKsPknARegulates cell shape; essential; transmembrane
PknBRegulates cell shape; essential; transmembrane
PknFPhosphorylates putative ABC transporter of M. tuberculosis (Rv1747); transmembrane
PknGModulates macrophage response to infection; essential; soluble
PknHPhosphorylates the OmpR-like EmbR transcription factor; transmembrane
PknKSoluble
PknC, -D, -E, -I, -J, -LTransmembrane
WhiB genesThought to bind DNA and influence transcription as well as play a role in sensing intracellular redox state; M. tuberculosis encodes 7 WhiB homologuesWhiB2Possibly involved in cell wall remodeling and cell division
WhiB3Interacts with RpoV and is important for pathogenesis within the host
WhiB4May be a sensor of oxidative stress
WhiB1, -5, -6, -7Unknown
TCSsTransfers a phosphate from the histidine residue on the autophosphorylated sensor to the aspartate residue on the response regulator to relay signals from the environment; M. tuberculosis encodes 11 TCSs in total (some not listed)DosRS/TDormancy survival
MtrABProliferation in macrophages
SenX3-RegX3May regulate phosphate-dependent gene expression
MprABGrowth during persistent stage
PhoPRImplicated in regulating production of complex cell wall lipids
Alternative sigma factorsThe largest subset are known as ECF sigma factors and are small regulatory proteins lacking some of the conserved regions of typical sigma factors; M. tuberculosis encodes 13 sigma factors, 10 of which are ECF sigma factors (some not listed)SigB, -D, -E, -HRegulate genes that allow bacteria to adapt to stress
TA systemOriginally recognized as a mechanism for ensuring proper plasmid segregation, the TA loci have now been shown to have diverse roles; works by production of a stable toxin and an unstable antitoxin, thus requiring a constant supply of antitoxin; M. tuberculosis has 38 TA loci (some not listed)3 RelBE homologues and 9 MazEF homologuesToxins that cleave mRNA in response to nutrient stress or starvation
Stringent responseRelA is triggered by uncharged tRNAs at the ribosomal A site during carbon starvation and synthesizes P4G, which binds RNA polymerase, reducing the promoter open-complex half-life and halting translationRelASynthesizes P4G
SpoTHydrolyzes P4G