Dataset Information

Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

ABSTRACT: Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.

SUBMITTER: Porse A

PROVIDER: S-EPMC5388698 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

Porse Andreas A Gumpert Heidi H Kubicek-Sutherland Jessica Z JZ Karami Nahid N Adlerberth Ingegerd I Wold Agnes E AE Andersson Dan I DI Sommer Morten O A MOA

Frontiers in cellular and infection microbiology 20170412

Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut ...[more]

PMID: 28447026

Similar Datasets

Project description:Studies of Escherichia coli in the human gastrointestinal tract have focused on pathogens, such as diarrhea-causing enterotoxigenic E. coli (ETEC), while overlooking the resident, nonpathogenic E. coli community. Relatively few genomes of nonpathogenic E. coli strains are available for comparative genomic analysis, and the ecology of these strains is poorly understood. This study examined the diversity and dynamics of resident human gastrointestinal E. coli communities in the face of the ecological challenges presented by pathogen (ETEC) challenge, as well as of antibiotic treatment. Whole-genome sequences obtained from E. coli isolates from before, during, and after ETEC challenge were used in phylogenomic and comparative genomic analyses to examine the diversity of the resident E. coli communities, as well as the dynamics of the challenge strain, H10407, a well-studied ETEC strain (serotype O78:H11) that produces both heat-labile and heat-stable enterotoxins. ETEC failed to become the dominant E. coli clone in two of the six challenge subjects, each of whom exhibited limited or no clinical presentation of diarrhea. The E. coli communities of the remaining four subjects became ETEC dominant during the challenge but reverted to their original, subject-specific populations following antibiotic treatment, suggesting resiliency of the resident E. coli population following major ecological disruptions. This resiliency is likely due in part to the abundance of antibiotic-resistant ST131 E. coli strains in the resident populations. This report provides valuable insights into the potential interactions of members of the gastrointestinal microbiome and its responses to challenge by an external pathogen and by antibiotic exposure. IMPORTANCE Research on human-associated E. coli tends to focus on pathogens, such as enterotoxigenic E. coli (ETEC) strains, which are a leading cause of diarrhea in developing countries. However, the severity of disease caused by these pathogens is thought to be influenced by the microbiome. The nonpathogenic E. coli community that resides in the human gastrointestinal tract may play a role in pathogen colonization and disease severity and may become a reservoir for virulence and antibiotic resistance genes. Our study used whole-genome sequencing of E. coli before, during, and after challenge with an archetype ETEC isolate, H10407, and antibiotic treatment to explore the diversity and resiliency of the resident E. coli population in response to the ecological disturbances caused by pathogen invasion and antibiotic treatment.

Project description:In the present study, it is shown that although Escherichia coli CFT073, a human uropathogenic (UPEC) strain, grows in liquid glucose M9 minimal medium, it fails to grow on glucose M9 minimal medium agar plates seeded with ?10(6) CFU. The cells on glucose plates appear to be in a "quiescent" state that can be prevented by various combinations of lysine, methionine, and tyrosine. Moreover, the quiescent state is characteristic of ~80% of E. coli phylogenetic group B2 multilocus sequence type 73 strains, as well as 22.5% of randomly selected UPEC strains isolated from community-acquired urinary tract infections in Denmark. In addition, E. coli CFT073 quiescence is not limited to glucose but occurs on agar plates containing a number of other sugars and acetate as sole carbon sources. It is also shown that a number of E. coli CFT073 mini-Tn5 metabolic mutants (gnd, gdhA, pykF, sdhA, and zwf) are nonquiescent on glucose M9 minimal agar plates and that quiescence requires a complete oxidative tricarboxylic acid (TCA) cycle. In addition, evidence is presented that, although E. coli CFT073 quiescence and persistence in the presence of ampicillin are alike in that both require a complete oxidative TCA cycle and each can be prevented by amino acids, E. coli CFT073 quiescence occurs in the presence or absence of a functional rpoS gene, whereas maximal persistence requires a nonfunctional rpoS. Our results suggest that interventions targeting specific central metabolic pathways may mitigate UPEC infections by interfering with quiescence and persistence. IMPORTANCE Recurrent urinary tract infections (UTIs) affect 10 to 40% of women. In up to 77% of those cases, the recurrent infections are caused by the same uropathogenic E. coli (UPEC) strain that caused the initial infection. Upon infection of urothelial transitional cells in the bladder, UPEC appear to enter a nongrowing quiescent intracellular state that is thought to serve as a reservoir responsible for recurrent UTIs. Here, we report that many UPEC strains enter a quiescent state when ?10(6) CFU are seeded on glucose M9 minimal medium agar plates and show that mutations in several genes involved in central carbon metabolism prevent quiescence, as well as persistence, possibly identifying metabolic pathways involved in UPEC quiescence and persistence in vivo.

Dataset Information

Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

Publications

Genome Dynamics of <i>Escherichia coli</i> during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements <i>In situ</i> of the Infant Gut.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets