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.
Highlights
The phenomenon of protective clearance of antibiotics by resistant cells is commonly seen by microbiologists in the presence of ‘satellite’ colonies on transformation plates (Figure 1a)
Antibiotic resistance conferred by the enzymatic breakdown of drugs is potentially a cooperative trait as it can detoxify the environment for all cells, and the production of β-lactamases, which cleave and deactivate penicillins, is often cited as a social trait in bacteria (West et al, 2006; Diggle et al, 2007; Brown et al, 2009)
Cross-species protection of susceptible bacteria by β-lactamase producers has been seen in vivo (Tacking, 1954; Hackman and Wilkins, 1975; Brook et al, 1983), suggesting that the benefits of β-lactamase enzymes may spread to entire communities
Summary
The phenomenon of protective clearance of antibiotics by resistant cells is commonly seen by microbiologists in the presence of ‘satellite’ colonies on transformation plates (Figure 1a). These nonresistant colonies are able to grow on ampicillin plates where resistant colonies are already established. Bacteria do have mechanisms that enable them to escape or tolerate the effects of bactericidal antibiotics, one being a ‘persister’ state colonies grow on ampicillin plates in the presence of resistant in which dormant cells can survive exposure to colonies (bottom row), but not alone (top row). Persister cells were identified early in the clinical life of penicillin (Bigger, 1944), but a recent resurgence in interest has been fuelled by a wider appreciation of their clinical
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