Systematic Investigation of Resistance Evolution to Common Antibiotics Reveals Conserved Collateral Responses across Common Human Pathogens

Abstract

As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will increasingly be relied upon to treat infections and to slow the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic effects a specific organism's collateral response to a wide variety of antibiotics. Results of these studies have been used to identify networks of drugs which can be used to drive resistance in a particular direction. However, little is known about the extent of evolutionary conservation of these responses across species. We sought to address this knowledge gap by performing a systematic resistance evolution study of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) under uniform growth conditions using five clinically relevant antibiotics with diverse modes of action. Evolved lineages were analyzed for collateral effects and the molecular mechanisms behind the observed phenotypes. Fourteen universal cross-resistance and two global collateral sensitivity relationships were found among the lineages. Genomic analyses revealed drug dependent divergent and conserved evolutionary trajectories amongst the pathogens. Our findings suggest that collateral responses may be preserved across species. These findings may help extend the contribution of previous collateral network studies in the development of treatment strategies to address the problem of antibiotic resistance.

The Effect of Shock Gentamicin Concentrations on the Formation of Resistance and Small Colony Variants in <i>Staphylococcus aureus</i>

“…Существует предположение, что изменение клеточного дыхания за счёт изменения работы электрон-транспортной цепи влияет на электрический потенциал мембраны, что в свою очередь, влияет на пенетрацию аминогликозидов внутрь клетки [25]. Мутации в гене fusA, обуславливают устойчивость к фузидиевой кислоте, а также к аминогликозидам [26]. В настоящем исследовании только у одного штамма была выявлена мутация в fusA, без изменений чувствительности к фузидиевой кислоте.…”

Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies

“…The evolutionary conservation of collateral responses to five clinically relevant antibiotics (cefepime, ciprofloxacin, gentamicin, meropenem, and tetracycline) across species, particularly within the ESKAPE pathogens, was investigated [60]. This study identified 14 instances of universal cross-resistance that accounted for 80% of all the collateral responses and two global collateral sensitivity relationships (cefepime and gentamicin pair and ciprofloxacin and gentamicin pair) among the evolved lineages [60]. Although the genetic basis for the collateral sensitivity was unclear, genomic analyses revealed divergent and conserved evolutionary trajectories, suggesting that collateral responses may be preserved across species for the selected drugs [60].…”

“…This study identified 14 instances of universal cross-resistance that accounted for 80% of all the collateral responses and two global collateral sensitivity relationships (cefepime and gentamicin pair and ciprofloxacin and gentamicin pair) among the evolved lineages [60]. Although the genetic basis for the collateral sensitivity was unclear, genomic analyses revealed divergent and conserved evolutionary trajectories, suggesting that collateral responses may be preserved across species for the selected drugs [60].…”

Adaptive laboratory evolution to hypersaline conditions of lactic acid bacteria isolated from seaweed

“…It was demonstrated [34] that when a strain of E. faecium was exposed to stress events, such as sub-lethal concentrations of NaCl, it showed an improved adaptation to a second stress episodeat increased heat levels. The resistance of individual isolates is supposed to be improved, following that one of the bacterial population [35]. However, isolates-outliers with decreased resistance compared to their corresponding populations can be detected because of sample storage at -80°C, before use.…”