Bacteria Share Drug Resistance Plasmids in Chickens without Drug Selection
In an effort to halt selection for drug-resistant bacterial growth in livestock, the FDA has changed the way that antibiotics will be used on farms. While antibiotics are allowed for treating sick animals, or to prevent illness when disease is likely, the use of antibiotic drugs in animal feed as growth promoters is no longer permitted. These changes are aimed at halting the selection and spread of drug-resistant bacteria in livestock animals, which play an important role in drug-resistant infections in people.
But will halting the use of antibiotics in livestock work? Will it stop resistant bacteria from growing or passing their resistance genes to other organisms? The underlying concept is that plasmids have a high fitness cost to bacteria carrying them, so bacterial populations without resistant plasmids will outgrow the resistant population when the drug is not present. A new Antimicrobial Agents and Chemotherapy report counters this often-cited narrative by demonstrating the in vivo transfer of a plasmid conferring carbapenem resistance between Salmonella enterica subsp. enterica serovar Corvallis (S. Corvallis) and other bacterial species in the guts of broiler chickens.
First author Sean Hadziabdic and senior scientist Istvan Szabo and the scientific team examined the spread of both resistant bacteria and resistance genes in the absence of drug selection. They mimicked livestock-raising conditions as closely as possible for broiler chickens, which they then infected orally with S. Corvallis containing a carbapenem-resistance gene on a plasmid.
Within a week, the chickens were excreting S. Corvallis in their feces—but Salmonella weren’t the only bacteria now resistant to carbapenems. All experimental groups contained resistant E. coli in their feces, and one group contained resistant Klebsiella. Excretion of S. Corvallis continued for several weeks, suggesting the bacteria had taken residence and was replicating within the animals.
Whole-genome sequencing confirmed that the plasmid transferred to several E. coli sequence types. Although the bacteria shared carbapenem resistance, the plasmid itself was altered after moving into other Enterobacteriaceae. Plasmid rearrangements did not affect carbapenem or other plasmid-encoded resistance genes. The discovery of multiple plasmid rearrangements along with the original plasmid sequence suggested that multiple plasmid-containing populations were growing inside the chickens.
Many microbiologists are taught that plasmid carriage has a high fitness cost; this is the reason why all selection media for cloning must contain antibiotic, to avoid plasmid loss and subsequent outgrowth of a plasmid-free strain. The Antimicrobial Agents and Chemotherapy report suggests that drug use is unnecessary either for the maintenance of a plasmid-containing population or for the transfer of that resistance plasmid. The data help explain the spread of plasmid-mediated carbapenemase resistance not only within livestock populations, but also among wild birds presumably naïve to antibiotic exposure.
What does this mean for farms that have transitioned to using antibiotics only when needed, rather than administering small doses as growth promoters? The good news is that new mutations are less likely to be selected for without the presence of drug (although it is not impossible!). However, resistant bacterial strains that once colonized the farm or nearby animals may continue to propagate and transfer their resistance genes within the animals. The take-home message is that eliminating drug-resistant bacteria from our food supply may be more complicated than simply decreasing antibiotic use.