Journal
CURRENT OPINION IN MICROBIOLOGY
Volume 61, Issue -, Pages 107-114Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.mib.2021.03.007
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Funding
- University of Minnesota [N.I.H.R01 GM13453801A1]
- UMN Office of Academic Clinical Affairs
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Targeting bacterial signaling through two-component systems (TCSs) and developing inhibitors that target the HK ATP-binding domain may be effective strategies in combating antimicrobial resistance.
With the rise in antimicrobial resistance and the dearth of effective strategies to combat this threat, the development of novel therapies is of utmost importance. Targeting of bacterial signaling through their the two-component systems (TCSs) may be a viable strategy. TCSs are comprised of a sensory histidine kinase (HK), of which a bacterium can have up to 160 distinct proteins, and a cognate response regulator (RR). The TCSs are generally non-essential for life, but control many virulence and antibiotic-resistance mechanisms. This, along with their absence in animals makes the TCSs an attractive target for antimicrobial therapy, whether as a stand-alone treatments or adjuvants for existing therapies. This review focuses on progress in the development of inhibitors that target the HK ATP-binding domain. Because this domain is highly conserved, it may be feasible to disrupt multiple TCSs within a single organism to increase effectiveness and reduce pressure for the evolution of resistance.
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