Bacterial charity work leads to population-wide resistance. Nature

Howard Hughes Medical Institute, Center for BioDynamics, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 09/2010; 467(7311):82-5. DOI: 10.1038/nature09354
Source: PubMed


Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population's less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

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    • "Antibiotic resistance mechanisms, which appear de novo or are transmitted among bacteria, have been well studied and described in many reviews. These include detoxification of antibiotic molecules and mutations in the designated target or, as described recently, are mediated by population-level resistance mechanisms [1]. It is now apparent that interspecies and intraspecies horizontal gene transfer of both Gram-negative and Gram-positive bacteria represent the dominant process by which bacteria become multiresistant. "
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    ABSTRACT: Concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and other Enterobacteriaceae species represent a major public health burden. Despite the pharmaceutical sector’s lack of interest in the topic in the last decade, microbial natural products continue to represent one of the most interesting sources for discovering and developing novel antibacterials. Research in microbial natural product screening and development is currently benefiting from progress that has been made in other related fields (microbial ecology, analytical chemistry, genomics, molecular biology, and synthetic biology). In this paper, we review how novel and classical approaches can be integrated in the current processes for microbial product screening, fermentation, and strain improvement.
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    • "Although most of the research in this area has focused on collective action in the form of provision of public goods (Griffin et al., 2004; Gore et al., 2009; Cordero et al., 2012), it is clear that club and charity goods are also common in microbes. First, cases of " altruistic sacrifice " (West et al., 2006), " self-destructive cooperation " (Ackermann et al., 2008), and " bacterial charity work " (Lee et al., 2010), by which providers release chemical substances that benefit shirkers, are clear examples of charity goods. Second, " greenbeards " (Gardner and West, 2010; Queller, 2011), where providers produce an excludable good such as adherence or food sources (Smukalla et al., 2008; White and Winans, 2007), are examples of club goods. "
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    • "(e.g., glycylcyclines), macrolides (e.g., erythromycin and rifamycin analogues), spectinomycins, glycopeptides (e.g., vancomycin and teicoplanin analogues), flavonoids, alkaloids, and quinones, among others (Baquero, 1997; Clardy et al., 2006; Saleem et al., 2010 "
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