Dataset Information

Within-host dynamics shape antibiotic resistance in commensal bacteria.

ABSTRACT: The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically explicit within-host dynamics in a structurally neutral pathogen transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition.

SUBMITTER: Davies NG

PROVIDER: S-EPMC6420107 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Within-host dynamics shape antibiotic resistance in commensal bacteria.

Davies Nicholas G NG Flasche Stefan S Jit Mark M Atkins Katherine E KE

Nature ecology & evolution 20190211 3

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range ...[more]

PMID: 30742105

Similar Datasets

Project description:Colonization of the infant gut is an important developmental process characterized by high carriage of antimicrobial resistance genes (ARGs) and high abundances of pathobionts. The horizontal transfer of ARGs to pathogenic bacteria represents a major public health concern. However, there is still a paucity of longitudinal studies surveilling ARGs in healthy infant guts at high temporal resolution. Furthermore, we do not yet have a clear view of how temporal variation in ARG carriage relates to the dynamics of specific bacterial populations, as well as community virulence potential. Here, we performed deep shotgun metagenomic sequencing of monthly fecal samples from a cohort of 12 infants, covering the first year of life to interrogate the infant gut microbiome for ARG content. We further relate ARG dynamics to the dynamics of taxa, virulence potential, as well as the potential for ARG mobilization. We identify a core resistome dominated by efflux systems typically associated with Enterobacteriaceae. Overall ARG carriage declined over the first year of life and showed strong contemporaneous correlation with the population dynamics of Proteobacteria. Furthermore, the majority of ARGs could be further mapped to metagenome-assembled genomes (MAGs) classified to this phylum. We were able to assign a large number of ARGs to E. coli by correlating the temporal dynamics of individual genes with species dynamics, and we show that the temporal dynamics of ARGs and virulence factors are highly correlated, suggesting close taxonomic associations between these two gene classes. Finally, we identify ARGs linked with various categories of mobile genetic elements, demonstrating preferential linkage among mobility categories and resistance to different drug classes. While individual variation in ARG carriage is substantial during infancy there is a clear reduction over the first year of life. With few exceptions, ARG abundances closely track the dynamics of pathobionts and community virulence potential. These findings emphasize the potential for development of resistant pathogens in the developing infant gut, and the importance of effective surveillance in order to detect such events.

Project description:Conflict within mutually beneficial associations is predicted to destabilize relationships, and theoretical and empirical work exploring this has provided significant insight into the dynamics of cooperative interactions. Within mutualistic associations, the expression and regulation of conflict is likely more complex than in intraspecific cooperative relationship, because of the potential presence of: i) multiple genotypes of microbial species associated with individual hosts, ii) multiple species of symbiotic lineages forming cooperative partner pairings, and iii) additional symbiont lineages. Here we explore complexity of conflict expression within the ancient and coevolved mutualistic association between attine ants, their fungal cultivar, and actinomycetous bacteria (Pseudonocardia). Specifically, we examine conflict between the ants and their Pseudonocardia symbionts maintained to derive antibiotics against parasitic microfungi (Escovopsis) infecting the ants' fungus garden. Symbiont assays pairing isolates of Pseudonocardia spp. associated with fungus-growing ants spanning the phylogenetic diversity of the mutualism revealed that antagonism between strains is common. In contrast, antagonism was substantially less common between more closely related bacteria associated with Acromyrmex leaf-cutting ants. In both experiments, the observed variation in antagonism across pairings was primarily due to the inhibitory capabilities and susceptibility of individual strains, but also the phylogenetic relationships between the ant host of the symbionts, as well as the pair-wise genetic distances between strains. The presence of antagonism throughout the phylogenetic diversity of Pseudonocardia symbionts indicates that these reactions likely have shaped the symbiosis from its origin. Antagonism is expected to prevent novel strains from invading colonies, enforcing single-strain rearing within individual ant colonies. While this may align ant-actinomycete interests in the bipartite association, the presence of single strains of Pseudonocardia within colonies may not be in the best interest of the ants, because increasing the diversity of bacteria, and thereby antibiotic diversity, would help the ant-fungus mutualism deal with the specialized parasites.

Project description:Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where disease severity lessened with time, and the pathogen evolved towards a commensal relationship with the host. In the current study, we used whole-genome sequencing to monitor this long-term symbiotic relationship to better understand B. pseudomallei persistence in P314's sputum despite intensive initial therapeutic regimens. We collected and sequenced 118 B. pseudomallei isolates from P314's airways over a >16-year period, and also sampled the patient's home environment, recovering six closely related B. pseudomallei isolates from the household water system. Using comparative genomics, we identified 126 SNPs in the core genome of the 124 isolates or 162 SNPs/indels when the accessory genome was included. The core SNPs were used to construct a phylogenetic tree, which demonstrated a close relationship between environmental and clinical isolates and detailed within-host evolutionary patterns. The phylogeny had little homoplasy, consistent with a strictly clonal mode of genetic inheritance. Repeated sampling revealed evidence of genetic diversification, but frequent extinctions left only one successful lineage through the first four years and two lineages after that. Overall, the evolution of this population is nonadaptive and best explained by genetic drift. However, some genetic and phenotypic changes are consistent with in situ adaptation. Using a mouse model, P314 isolates caused greatly reduced morbidity and mortality compared to the environmental isolates. Additionally, potentially adaptive phenotypes emerged and included differences in the O-antigen, capsular polysaccharide, motility, and colony morphology. The >13-year co-existence of two long-lived lineages presents interesting hypotheses that can be tested in future studies to provide additional insights into selective pressures, niche differentiation, and microbial adaptation. This unusual melioidosis case presents a rare example of the evolutionary progression towards commensalism by a highly virulent pathogen within a single human host.

Dataset Information

Within-host dynamics shape antibiotic resistance in commensal bacteria.

Publications

Within-host dynamics shape antibiotic resistance in commensal bacteria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets