Species interactions drive the spread of ampicillin resistance in human-associated gut microbiota

BACKGROUND AND OBJECTIVES: Slowing the spread of antimicrobial resistance is urgent if we are to continue treating infectious diseases successfully. There is increasing evidence microbial interactions between and within species are significant drivers of resistance. On one hand, cross-protection by resistant genotypes can shelter susceptible microbes from the adverse effects of antibiotics, reducing the advantage of resistance. On the other hand, antibiotic-mediated killing of susceptible genotypes can alleviate competition and allow resistant strains to thrive (competitive release). Here, by observing interactions both within and between species in microbial communities sampled from humans, we investigate the potential role for cross-protection and competitive release in driving the spread of ampicillin resistance in the ubiquitous gut commensal and opportunistic pathogen Escherichia coli. METHODOLOGY: Using anaerobic gut microcosms comprising E.coli embedded within gut microbiota sampled from humans, we tested for cross-protection and competitive release both within and between species in response to the clinically important beta-lactam antibiotic ampicillin. RESULTS: While cross-protection gave an advantage to antibiotic-susceptible E.coli in standard laboratory conditions (well-mixed LB medium), competitive release instead drove the spread of antibiotic-resistant E.coli in gut microcosms (ampicillin boosted growth of resistant bacteria in the presence of susceptible strains). CONCLUSIONS AND IMPLICATIONS: Competition between resistant strains and other members of the gut microbiota can restrict the spread of ampicillin resistance. If antibiotic therapy alleviates competition with resident microbes by killing susceptible strains, as here, microbiota-based interventions that restore competition could be a key for slowing the spread of resistance. LAY SUMMARY: Slowing the spread of global antibiotic resistance is an urgent task. In this paper, we ask how interactions between microbial species drive the spread of resistance. We show that antibiotic killing of susceptible microbes can free up resources for resistant microbes and allow them to thrive. Therefore, we should consider microbes in light of their social interactions to understand the spread of resistance.