Stringent response induced by amino acid starvation not involved in mediating broad spectrum antibiotic resistance in Escherichia coli

Authors

  • Kabir Bhalla University of British Columbia
  • Jason Gravett
  • Paul Crichton
  • Ayse Nisan Erdogan

DOI:

https://doi.org/10.14288/ujemi.v25i.193148

Abstract

Antibiotic resistance is a global threat to human welfare. The widespread use of antibiotics combined with a stagnation in the field of antibiotic development and discovery has exacerbated the problem of antibiotic resistance. It has therefore become essential to understand evolutionarily conserved cell response pathways and their contributions to antibiotic resistance to overcome this health crisis and develop new, more effective therapeutics. One such conserved pathway is the stringent response. The stringent response allows bacteria like Escherichia coli to survive adverse conditions by causing a diversion of resources away from growth and division and toward prolonged survival. Previous research has demonstrated that activation of the stringent response in E. coli results in increased resistance to certain antibiotics, such as kanamycin. In this study, we investigated the effect of the stringent response on resistance to a variety of antibiotics in E. coli using wild type and a ΔrelA/ΔspoT mutant strains, as the ΔrelA/ΔspoT mutant is unable to elicit the stringent response. Five classes of antibiotics with diverse cellular targets including peptidoglycan synthesis, gene expression, and outer membrane stability were selected. We hypothesized that WT E. coli undergoing stringent response activation will experience a broad spectrum increase in antibiotic resistance when compared to the ΔrelA/ΔspoT mutant. Our results failed to replicate previous findings, refuted our hypothesis, and demonstrated that stringent response activation does not lead to a broad spectrum increase in antibiotic resistance.

Downloads

Additional Files

Published

2020-09-01