Roles of Multidrug Resistance Protein 4 in Microbial Infections and Inflammatory Diseases

Microb Drug Resist. 2021 Nov;27(11):1535-1545. doi: 10.1089/mdr.2020.0020. Epub 2021 May 17.

Abstract

Numerous studies have reported the emergence of antimicrobial resistance during the treatment of common infections. Multidrug resistance (MDR) leads to failure of antimicrobial treatment, prolonged illness, and increased morbidity and mortality. Overexpression of multidrug resistance proteins (MRPs) as drug efflux pumps are one of the main contributions of MDR, especially multidrug resistance protein 4 (MRP4/ABCC4) in the development of antimicrobial resistance. The molecular mechanism of antimicrobial resistance is still under investigation. Various intervention strategies have been developed for overcoming MDR, but the effect is limited. Suppression of MRP4 may be an attractive therapeutic approach for addressing drug resistance. However, there are few reports on the involvement of MRP4 in antimicrobial resistance and inflammatory diseases. In this review, we introduced the function and regulation of MRP4, and then summarized the roles of MRP4 in microbial infections and inflammatory diseases as well as polymorphisms in the gene encoding this transporter. Further studies should be conducted on drug therapy targeting MRP4 to improve the efficacy of antimicrobial therapy. This review can provide useful information on MRP4 for overcoming antimicrobial resistance and anti-inflammatory therapy.

Keywords: MDR; MRP4; antimicrobial resistance; drug target; microbial infections.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Drug Resistance, Microbial / physiology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / physiology*
  • Genes, Bacterial
  • Inflammation / physiopathology
  • Inflammation Mediators / metabolism
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Multidrug Resistance-Associated Proteins / genetics

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Multidrug Resistance-Associated Proteins