ADAPTIVE EVOLUTION OF HIGHLY MUTABLE LOCI IN PATHOGENIC BACTERIA PDF

Here, we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple patients. We conducted a retrospective study of a Burkholderia dolosa outbreak among people with cystic fibrosis, sequencing the genomes of isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired non-synonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes illuminate the genetic basis of important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition, and implicate oxygen-dependent gene regulation as paramount in lung infections. Several genes have not been previously implicated in pathogenesis, suggesting new therapeutic targets. The identification of parallel molecular evolution suggests key selection forces acting on pathogens within humans and can help predict and prepare for their future evolutionary course.

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Pathogens Key Points Whole-genome sequencing of several isolates from single hosts has revealed previously unsuspected within-host diversity of many bacterial pathogens. Within-host bacterial populations are subject to multifarious evolutionary forces including mutation, genetic drift, natural selection and fluctuating population size.

Within-host evolution limits the utility of sampling a single genome per host for reconstructing transmission relationships, conferring a benefit to sequencing several genomes per host. Resistance to some antimicrobials frequently evolves independently in individual hosts, revealing the substantial potential of bacteria to adapt in the human body. Within-host adaptation has a major role in the evolution of opportunistic infections in immunocompromised patients by otherwise free-living bacteria.

The study of within-host genomic evolution promises to shed light on whether pathogens tend to become more or less virulent within the host, and the selective pressures underlying this evolution. Abstract Whole-genome sequencing has opened the way for investigating the dynamics and genomic evolution of bacterial pathogens during the colonization and infection of humans. The application of this technology to the longitudinal study of adaptation in an infected host — in particular, the evolution of drug resistance and host adaptation in patients who are chronically infected with opportunistic pathogens — has revealed remarkable patterns of convergent evolution, suggestive of an inherent repeatability of evolution.

In this Review, we describe how these studies have advanced our understanding of the mechanisms and principles of within-host genome evolution, and we consider the consequences of findings such as a potent adaptive potential for pathogenicity. Finally, we discuss the possibility that genomics may be used in the future to predict the clinical progression of bacterial infections and to suggest the best option for treatment.

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Pathogens Key Points Whole-genome sequencing of several isolates from single hosts has revealed previously unsuspected within-host diversity of many bacterial pathogens. Within-host bacterial populations are subject to multifarious evolutionary forces including mutation, genetic drift, natural selection and fluctuating population size. Within-host evolution limits the utility of sampling a single genome per host for reconstructing transmission relationships, conferring a benefit to sequencing several genomes per host. Resistance to some antimicrobials frequently evolves independently in individual hosts, revealing the substantial potential of bacteria to adapt in the human body. Within-host adaptation has a major role in the evolution of opportunistic infections in immunocompromised patients by otherwise free-living bacteria. The study of within-host genomic evolution promises to shed light on whether pathogens tend to become more or less virulent within the host, and the selective pressures underlying this evolution. Abstract Whole-genome sequencing has opened the way for investigating the dynamics and genomic evolution of bacterial pathogens during the colonization and infection of humans.

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Within-host evolution of bacterial pathogens

Metrics details Abstract Because most newly arising mutations are neutral or deleterious, it has been argued 1 , 2 , 3 that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. We consider here whether high mutation rates might playan important role in adaptive evolution. Less potent mutators 10 to fold increase can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments 7. Download PDF Main Early models of the evolution of the mutation rate were based on group selection for an optimal compromise between adaptability and adaptedness 2 , 3.

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