Live to cheat another day: bacterial dormancy facilitates the social exploitation of β-lactamases

Abstract

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours.

Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium

“…β-lactamases) or by inducing susceptible cells to withstand antibiotic stress (Lee et al, 2010; Medaney et al, 2016; Yurtsev et al, 2013). To determine whether bacterial species within ARM differed in terms of antibiotic resistance, we plated a diluted suspension of ARM on media containing concentrations of ampicillin ranging from 0 to 500 μg/ml and determined bacterial composition by 16S rRNA gene sequencing.…”

Collective Resistance in Microbial Communities by Intracellular Antibiotic Deactivation

“…High cell densities and thus the presence of many drug target sites may be sufficient to lower the concentration of active compound by titration of free drug molecules [19]. Furthermore, antibiotic degradation via β-lactamase enables growth not only of resistant cells but also of susceptible cells in their vicinity [20–22], even across species, as demonstrated for amoxicillin-resistant H . influenzae and susceptible S .…”

Oscillatory dynamics in a bacterial cross-protection mutualism

“…The production of resistance enzymes is a common mechanism of antibiotic resistance (22) and can be considered cooperative because resistant cells can protect sensitive cells by reducing the concentration of active antibiotics in the environment, allowing their sensitive neighbors to survive an otherwise lethal exposure (19,(23)(24)(25)(26)(27)(28). Multiple examples of such protective interactions have been observed in clinically relevant strains where pathogenic, but otherwise sensitive, strains were protected against antibiotics by neighboring microbes (23,29,30).…”