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The human gut microbiome is the presumed site in which the emergence and evolution of antibiotic-resistant organisms constantly take place. To delineate the genetic basis of resistance formation in gut microbiome strains, we investigated the changes in the subpopulation structure of Escherichia coli in rat intestine before and after antimicrobial treatment. We observed that antibiotic treatment was selected for an originally minor subpopulation E. coli carrying the biofilm-forming genetic locus pgaABCD and the toxin-antitoxin system HipAB. Such strains possessed dramatically enhanced ability to withstand the detrimental effects of antibiotics, becoming a dominant subspecies upon antibiotic treatment and eventually evolving into resistant mutants. In contrast, E. coli strains that did not carry pgaABCD and HipAB were eradicated upon antibiotic treatment. Our findings, therefore, suggested that genes encoding biofilm-forming ability played an important role in conferring specific gut E. coli strains the ability to evolve into resistant strains upon a prolonged antibiotic treatment, and that such strains may therefore be considered bacterial antibiotic resistance progenitor cells in the gut microbiome.

The human gut microbiome is the presumed site in which the emergence and evolution of antibiotic-resistant organisms constantly take place. To delineate the genetic basis of resistance formation in gut microbiome strains, we investigated the changes in the subpopulation structure of Escherichia coli in rat intestine before and after antimicrobial treatment. We observed that antibiotic treatment was selected for an originally minor subpopulation E. coli carrying the biofilm-forming genetic locus pgaABCD and the toxin-antitoxin system HipAB . Such strains possessed dramatically enhanced ability to withstand the detrimental effects of antibiotics, becoming a dominant subspecies upon antibiotic treatment and eventually evolving into resistant mutants. In contrast, E. coli strains that did not carry pgaABCD and HipAB were eradicated upon antibiotic treatment. Our findings, therefore, suggested that genes encoding biofilm-forming ability played an important role in conferring specific gut E. coli strains the ability to evolve into resistant strains upon a prolonged antibiotic treatment, and that such strains may therefore be considered bacterial antibiotic resistance progenitor cells in the gut microbiome.