Non-antibiotics, Efflux Pumps and Drug Resistance of Gram-negative Rods

Pol J Microbiol. 2018 Jun 30;67(2):129-135. doi: 10.21307/pjm-2018-017.

Abstract

Non-antibiotic medicinal products consist of drugs with diverse activity against bacteria. Many non-antibiotics demonstrate direct anti-bacterial activity against Gram-positive cocci. The activity observed against Gram-negative rods is much lower and non-antibiotics primarily from the following groups: non-steroidal anti-inflammatory drugs, cardiovascular and antidepressant medicinal products demonstrate this activity. It has been shown that the low activity of some non-antibiotics or the absence of activity against Gram-negative rods is related, among other things, to the extrusion of these compounds from bacterial cells by multi-drug resistance efflux pumps. Substrates for the resistance-nodulation-division efflux systems include the following non-antibiotics: salicylate, diclofenac, ibuprofen, mefenamic acid, naproxen, amitriptyline, alendronate sodium, nicergoline, and ticlopidine. In addition, interactions between non-antibiotics and multi-drug resistance efflux pumps have been observed. It has also been revealed that depending on the concentration, salicylate induces expression of multi-drug resistance efflux pumps in Escherichia coli, Salmonella enterica subsp. enterica serotype Typhimurium, and Burkholderia cenocepacia. However, salicylate does not affect the expression of the resistance-nodulation-division efflux systems in Stenotrophomonas maltophilia and Acinetobacter baumannii. Most importantly, there were no effects of medicinal products containing some non-antibiotic active substances, except salicylate, as substrates of multi-drug resistance efflux pumps, on the induction of Gram-negative rod resistance to quinolones.

Keywords: Escherichia coli; MDR efflux pumps; Pseudomonas aeruginosa; antibiotic resistance; non-antibiotics.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Drug Resistance, Multiple, Bacterial*
  • Escherichia coli / drug effects
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Microbial Sensitivity Tests
  • Naproxen / pharmacology
  • Pseudomonas aeruginosa / drug effects
  • Salicylates / pharmacology

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Membrane Transport Proteins
  • Salicylates
  • Naproxen