Bacterial charity work leads to population-wide resistance | |
Article | |
关键词: ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; INDUCED MUTAGENESIS; EVOLUTION; INDOLE; DEATH; ADAPTATION; EXPRESSION; MUTATIONS; STRAINS; | |
DOI : 10.1038/nature09354 | |
来源: SCIE |
【 摘 要 】
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(1-7). 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(8). 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(9) 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.
【 授权许可】
Free