Gene flux and acid-imposed selection are the main drivers of antimicrobial resistance in broiler chicks infected withSalmonella entericaserovar Heidelberg
Authors: Oladeinde Adelumola , Abdo Zaid , Press Maximilian O. , Cook Kimberly , Cox Nelson A. , Zwirzitz Benjamin , Woyda Reed , Lakin Steven M. , Thomas Jesse C. , Looft Torey , Cosby Douglas E. , Hinton Arthur , Guard Jean , Line Eric , Rothrock Michael J. , Berrang Mark E. , Herrington Kyler , Zock Gregory , Lawrence Jodie Plumblee , Cudnik Denice , House Sandra , Ingram Kimberly , Lariscy Leah , Wagner Martin , Aggrey Samuel E. , Chai Lilong , Ritz Casey 
Published: February 2021

AbstractAntimicrobial resistance (AR) spread is a worldwide health challenge, stemming in large part, from the ability of microbes to share their genetic material through horizontal gene transfer (HGT). Overuse and misuse of antibiotics in clinical settings and in food production have been linked to this increased prevalence and spread of AR. Consequently, public health and consumer concerns have resulted in a remarkable recent reduction in antibiotics used for food animal production. This is driven by the assumption that removing this selective pressure will favor the recovery of antibiotic susceptible taxa and will limit AR sharing through HGT, allowing the currently available antibiotic arsenal to be effective for a longer period. In this study we used broiler chicks raised antibiotic-free andSalmonella entericaserovar Heidelberg (SH), as a model food pathogen, to test this hypothesis. Our results show that neonatal broiler chicks challenged with an antibiotic susceptible SH strain and raised without antibiotics carried susceptible and multidrug resistance SH strains 14 days after challenge. SH infection perturbed the microbiota of broiler chicks and gavaged chicks acquired antibiotic resistant SH at a higher rate. We determined that the acquisition of a plasmid from commensalEscherichia colipopulation conferred multidrug resistance phenotype to SH recipients and carriage of this plasmid increased the fitness of SH under acidic selection pressure. These results suggest that HGT of AR shaped the evolution of SH and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria toSalmonella.ImportanceThe reported increase in antibiotic resistant bacteria in humans have resulted in a major shift away from antibiotics use in food animal production. This has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, and this in turn will allow the currently available antibiotic arsenal to be more effective. This shift in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic susceptibleSalmonellaHeidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggests that simply removing antibiotics from food-animal production might not be sufficient to limit the spread of antimicrobial resistance.