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A Bayesian model of acquisition and clearance of bacterial colonization incorporating within-host variation.

ABSTRACT: Bacterial populations that colonize a host can play important roles in host health, including serving as a reservoir that transmits to other hosts and from which invasive strains emerge, thus emphasizing the importance of understanding rates of acquisition and clearance of colonizing populations. Studies of colonization dynamics have been based on assessment of whether serial samples represent a single population or distinct colonization events. With the use of whole genome sequencing to determine genetic distance between isolates, a common solution to estimate acquisition and clearance rates has been to assume a fixed genetic distance threshold below which isolates are considered to represent the same strain. However, this approach is often inadequate to account for the diversity of the underlying within-host evolving population, the time intervals between consecutive measurements, and the uncertainty in the estimated acquisition and clearance rates. Here, we present a fully Bayesian model that provides probabilities of whether two strains should be considered the same, allowing us to determine bacterial clearance and acquisition from genomes sampled over time. Our method explicitly models the within-host variation using population genetic simulation, and the inference is done using a combination of Approximate Bayesian Computation (ABC) and Markov Chain Monte Carlo (MCMC). We validate the method with multiple carefully conducted simulations and demonstrate its use in practice by analyzing a collection of methicillin resistant Staphylococcus aureus (MRSA) isolates from a large recently completed longitudinal clinical study. An R-code implementation of the method is freely available at: https://github.com/mjarvenpaa/bacterial-colonization-model.

SUBMITTER: Jarvenpaa M

PROVIDER: S-EPMC6497309 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A Bayesian model of acquisition and clearance of bacterial colonization incorporating within-host variation.

Järvenpää Marko M Sater Mohamad R Abdul MRA Lagoudas Georgia K GK Blainey Paul C PC Miller Loren G LG McKinnell James A JA Huang Susan S SS Grad Yonatan H YH Marttinen Pekka P

PLoS computational biology 20190422 4

Bacterial populations that colonize a host can play important roles in host health, including serving as a reservoir that transmits to other hosts and from which invasive strains emerge, thus emphasizing the importance of understanding rates of acquisition and clearance of colonizing populations. Studies of colonization dynamics have been based on assessment of whether serial samples represent a single population or distinct colonization events. With the use of whole genome sequencing to determi ...[more]

PMID: 31009452

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Project description:The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. difficile colonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clear C. difficile colonization. We treated mice with titrated doses of antibiotics prior to C. difficile challenge, resulting in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously cleared C. difficile Therefore, we investigated whether other antibiotics would show the same result. We found that reduced doses of cefoperazone and streptomycin permitted colonization and clearance of C. difficile Mice that cleared colonization had antibiotic-specific community changes and predicted interactions with C. difficile Clindamycin treatment led to a bloom in populations related to Enterobacteriaceae Clearance of C. difficile was concurrent with the reduction of those blooming populations and the restoration of community members related to the Porphyromonadaceae and Bacteroides Cefoperazone created a susceptible community characterized by drastic reductions in the community diversity and interactions and a sustained increase in the abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of the Porphyromonadaceae, with little overlap in the specific Porphyromonadaceae observed in the clindamycin treatment. Further elucidation of how C. difficile colonization is cleared from different gut bacterial communities will improve C. difficile infection treatments.IMPORTANCE The community of microorganisms, or microbiota, in our intestines prevents pathogens like C. difficile from colonizing and causing infection. However, antibiotics can disturb the gut microbiota, which allows C. difficile to colonize. C. difficile infections (CDI) are primarily treated with antibiotics, which frequently leads to recurrent infections because the microbiota has not yet returned to a resistant state. The recurrent infection cycle often ends when the fecal microbiota from a presumed resistant person is transplanted into the susceptible person. Although this treatment is highly effective, we do not understand the mechanism. We hope to improve the treatment of CDI through elucidating how the bacterial community eliminates CDI. We found that C. difficile colonized susceptible mice but was spontaneously eliminated in an antibiotic treatment-specific manner. These data indicate that each community had different requirements for clearing colonization. Understanding how different communities clear colonization will reveal targets to improve CDI treatments.

Dataset Information

A Bayesian model of acquisition and clearance of bacterial colonization incorporating within-host variation.

Publications

A Bayesian model of acquisition and clearance of bacterial colonization incorporating within-host variation.

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