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Bacterial charity work leads to population-wide resistance.

ABSTRACT: 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.

SUBMITTER: Lee HH

PROVIDER: S-EPMC2936489 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Bacterial charity work leads to population-wide resistance.

Lee Henry H HH Molla Michael N MN Cantor Charles R CR Collins James J JJ

Nature 20100901 7311

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 a ...[more]

PMID: 20811456

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Project description:Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18-70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4-3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7-1.2; men: 4.3%; 95% CI 3.7-5.0). In the fully adjusted model, male gender (OR 3.16) and age 18-29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational injuries. While the odds for most work-related factors were as expected, the associations for health-related factors such as smoking, drinking, and chronic diseases were rather weak. In part, this may be due to context-specific factors such as safety and workplace regulations in high-income countries like Germany. This assumption could guide further research, taking a multi-level approach to international comparisons.

Project description:BackgroundA range of resistance loci against different races of Xanthomonas oryzae pv. oryzae (Xoo), the pathogen causing bacterial blight (BB) disease of rice, have been discovered and characterized. Several have been deployed in modern varieties, however, due to rapid evolution of Xoo, a number have already become ineffective. The continuous "arms race" between Xoo and rice makes it imperative to discover new resistance loci to enable durable deployment of multiple resistance genes in modern breeding lines. Rice diversity panels can be exploited as reservoirs of useful genetic variation for bacterial blight (BB) resistance. This study was conducted to identify loci associated to BB resistance, new genetic donors and useful molecular markers for marker-assisted breeding.ResultsA genome-wide association study (GWAS) of BB resistance using a diverse panel of 285 rice accessions was performed to identify loci that are associated with resistance to nine Xoo strains from the Philippines, representative of eight global races. Single nucleotide polymorphisms (SNPs) associated with differential resistance were identified in the diverse panel and a subset of 198 indica accessions. Strong associations were found for novel SNPs linked with known bacterial blight resistance Xa genes, from which high utility markers for tracking and selection of resistance genes in breeding programs were designed. Furthermore, significant associations of SNPs in chromosomes 6, 9, 11, and 12 did not overlap with known resistance loci and hence might prove to be novel sources of resistance. Detailed analysis revealed haplotypes that correlated with resistance and analysis of putative resistance alleles identified resistant genotypes as potential donors of new resistance genes.ConclusionsThe results of the GWAS validated known genes underlying resistance and identified novel loci that provide useful targets for further investigation. SNP markers and genetic donors identified in this study will help plant breeders in improving and diversifying resistance to BB.

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Bacterial charity work leads to population-wide resistance.

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Bacterial charity work leads to population-wide resistance.

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