Dataset Information

Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants.

ABSTRACT: The fitness cost to bacteria of acquisition of resistance determinants is critically under-investigated, and the identification and exploitation of these fitness costs may lead to novel therapeutic strategies that prevent the emergence of antimicrobial resistance. Here we used Escherichia coli and amoxicillin-clavulanic acid (AMC) resistance as a model to understand how the artificial environments utilized in studies of bacterial fitness could affect the emergence of resistance and associated fitness costs. Further, we explored the predictive value of this data when strains were grown in the more physiologically relevant environments of urine and urothelial organoids. Resistant E. coli isolates were selected for following 24-h exposure to sub-inhibitory concentrations of AMC in either M9, ISO, or LB, followed by growth on LB agar containing AMC. No resistant colonies emerged following growth in M9, whereas resistant isolates were detected from cultures grown in ISO and LB. We observed both within and between media-type variability in the levels of resistance and fitness of the resistant mutants grown in LB. MICs and fitness of these resistant strains in different media (M9, ISO, LB, human urine, and urothelial organoids) showed considerable variation. Media can therefore have a direct effect on the isolation of mutants that confer resistance to AMC and these mutants can exhibit unpredictable MIC and fitness profiles under different growth conditions. This preliminary study highlights the risks in relying on a single culture protocol as a model system to predict the behavior and treatment response of bacteria in vivo and highlights the importance of developing comprehensive experimental designs to ensure effective translation of diagnostic procedures to successful clinical outcomes.

SUBMITTER: Hubbard ATM

PROVIDER: S-EPMC6722461 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant <i>Escherichia coli</i> Mutants.

Hubbard Alasdair T M ATM Jafari Nazila V NV Feasey Nicholas N Rohn Jennifer L JL Roberts Adam P AP

Frontiers in microbiology 20190828

The fitness cost to bacteria of acquisition of resistance determinants is critically under-investigated, and the identification and exploitation of these fitness costs may lead to novel therapeutic strategies that prevent the emergence of antimicrobial resistance. Here we used <i>Escherichia coli</i> and amoxicillin-clavulanic acid (AMC) resistance as a model to understand how the artificial environments utilized in studies of bacterial fitness could affect the emergence of resistance and associ ...[more]

PMID: 31555237

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Project description:The role of canines in transmitting antibiotic resistant bacteria to humans in the urban environment is poorly understood. To elucidate this role, we utilized genomic sequencing and phylogenetics to characterize the burden and transmission dynamics of antibiotic resistant Escherichia coli (ABR-Ec) cultured from canine and human feces present on urban sidewalks in San Francisco, California. We collected a total of fifty-nine ABR-Ec from human (n=12) and canine (n=47) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antibiotic resistance (ABR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and canines from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Overall, we found human and canine samples to carry similar amounts and profiles of ABR genes. Our results provide evidence for multiple transmission events of ABR-Ec between humans and canines. In particular, we found one instance of likely transmission from canines to humans as well as an additional local outbreak cluster consisting of one canine and one human sample. Based on this analysis, it appears that canine feces act as an important reservoir of clinically relevant ABR-Ec within the urban environment. Our findings support that public health measures should continue to emphasize proper canine feces disposal practices, access to public toilets and sidewalk and street cleaning. Importance: Antibiotic resistance in E. coli is a growing public health concern with global attributable deaths projected to reach millions annually. Current research has focused heavily on clinical routes of antibiotic resistance transmission to design interventions while the role of alternative reservoirs such as domesticated animals remain less well understood. Our results suggest canines are part of the transmission network that disseminates high-risk multidrug resistance in E. coli within the urban San Francisco community. As such, this study highlights the need to consider canines, and potentially domesticated animals more broadly, when designing interventions to reduce the prevalence of antibiotic resistance in the community. Additionally, it showcases the utility of genomic epidemiology to reconstruct the pathways by which antimicrobial resistance spreads.

Dataset Information

Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants.

Publications

Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant <i>Escherichia coli</i> Mutants.

Similar Datasets

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