Roles of two-component regulatory systems in antibiotic resistance

Future Microbiol. 2019 Apr;14(6):533-552. doi: 10.2217/fmb-2019-0002. Epub 2019 May 8.

Abstract

Two-component regulatory systems (TCSs) are a major mechanism by which bacteria sense and respond to changes in their environment. TCSs typically consist of two proteins that bring about major regulation of the cell genome through coordinated action mediated by phosphorylation. Environmental conditions that activate TCSs are numerous and diverse and include exposure to antibiotics as well as conditions inside a host. The resulting regulatory action often involves activation of antibiotic defenses and changes to cell physiology that increase antibiotic resistance. Examples of resistance mechanisms enacted by TCSs contained in this review span those found in both Gram-negative and Gram-positive species and include cell surface modifications, changes in cell permeability, increased biofilm formation, and upregulation of antibiotic-degrading enzymes.

Keywords: antibiotic resistance; response regulator; sensor histidine kinase; signal transduction; two-component regulatory system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / genetics
  • Biofilms / growth & development
  • Cell Membrane Permeability
  • Drug Resistance, Bacterial / genetics
  • Drug Resistance, Bacterial / physiology*
  • Gene Expression Regulation, Bacterial / physiology
  • Genes, Bacterial / genetics
  • Histidine Kinase
  • Membrane Transport Proteins / physiology
  • Phosphorylation
  • Signal Transduction
  • Stress, Physiological
  • Up-Regulation

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Histidine Kinase