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 key for slowing the spread of resistance.