Two-component signal transduction as potential drug targets in pathogenic bacteria.
Gene clusters contributing to processes such as cell growth and pathogenicity are often controlled by two-component signal transduction systems (TCSs). Specific inhibitors against TCS systems work differently from conventional antibiotics, and developing them into new drugs that are effective against various drug-resistant bacteria may be possible. Furthermore, inhibitors of TCSs that control virulence factors may reduce virulence without killing the pathogenic bacteria. Previous TCS inhibitors targeting the kinase domain of the histidine kinase sensor suffered from poor selectivity. Recent TCS inhibitors, however, target the sensory domains of the sensors blocking the quorum sensing system, or target the essential response regulator. These new targets are introduced, together with several specific TCSs that have the potential to serve as effective drug targets.
Gotoh
Yasuhiro
Y
Department of Bioscience, Graduate School of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan.
Eguchi
Yoko
Y
Watanabe
Takafumi
T
Okamoto
Sho
S
Doi
Akihiro
A
Utsumi
Ryutaro
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D001424:Bacterial Infections / Q000382:microbiology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D000071677:Histidine Kinase; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014774:Virulence / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D000071677:Histidine Kinase