Two Component Regulatory Systems and Antibiotic Resistance in Gram-Negative Pathogens

Int J Mol Sci. 2019 Apr 10;20(7):1781. doi: 10.3390/ijms20071781.

Abstract

Gram-negative pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the leading cause of nosocomial infections throughout the world. One commonality shared among these pathogens is their ubiquitous presence, robust host-colonization and most importantly, resistance to antibiotics. A significant number of two-component systems (TCSs) exist in these pathogens, which are involved in regulation of gene expression in response to environmental signals such as antibiotic exposure. While the development of antimicrobial resistance is a complex phenomenon, it has been shown that TCSs are involved in sensing antibiotics and regulating genes associated with antibiotic resistance. In this review, we aim to interpret current knowledge about the signaling mechanisms of TCSs in these three pathogenic bacteria. We further attempt to answer questions about the role of TCSs in antimicrobial resistance. We will also briefly discuss how specific two-component systems present in K. pneumoniae, A. baumannii, and P. aeruginosa may serve as potential therapeutic targets.

Keywords: antimicrobial resistance; biofilms; two-component regulatory proteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Biofilms / growth & development*
  • Cross Infection / microbiology*
  • Cross Infection / therapy
  • Drug Resistance, Bacterial / physiology*
  • Gene Expression Regulation, Bacterial / physiology*
  • Gram-Negative Bacteria / physiology*
  • Gram-Negative Bacterial Infections / microbiology*
  • Gram-Negative Bacterial Infections / therapy
  • Humans