Abstract
BackgroundEmergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood.MethodsThis project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance.ResultsThere is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group).ConclusionsAntibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.
Highlights
Emergence of antibiotic resistance is a global public health concern
Antibiotic-induced changes in taxonomic composition of mouse gut Figure 1a-c presents the control samples allowing a comparison of species relative abundance before treatment with each antibiotic
This general trend in sample clustering was verified with ordination plots (PCoA) generated using 16S rRNA and Antibiotic resistance gene (ARG) abundance data, Figs. 6 and 8, respectively
Summary
Emergence of antibiotic resistance is a global public health concern. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. S. Centers for Disease Control and Prevention [1], the World Health Organization [2] as well as others [3] have identified proliferation of antimicrobial resistance as a global crisis. Antibiotics are globally used in the treatment of bacterial infections [4,5,6] and typically kill most antibioticsusceptible bacterial populations in a relatively short time. A small fraction of bacteria can survive and represent a major concern for emergent antibiotic resistance and recurrent infection [7]. When novel genetic mutations or resistance conducting plasmids appear, antibiotic-resistant strains can persist in the absence of this selective pressure contributing to the reservoir of antibiotic resistance [9]
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