Researchers Discover New Ways Plasmids Work to Make Bacteria More Resistant

Public health officials know that our ability to combat antibiotic resistance requires that we find solutions to the problem of superbugs faster than they can evolve and become stronger. In a recent study looking at bacterial genetics, researchers in Europe have found a new answer on just how pathogens quickly develop resistance.

Plasmids are small DNA molecules mostly found in bacterial cells, which are separate from and reproduce independently of chromosomal DNA. According to the Centers for Disease Control and Prevention, at least 2 million illnesses and 23,000 deaths in the United States each year are due to antibiotic resistance, as bacterial pathogens have continued to develop new ways to dodge treatment with antibiotic drugs. Public health experts studying the issue of resistance on a molecular level have noted the important role of plasmids in spreading the genes that make bacteria increasingly dangerous, but now new findings show that plasmids play an additional role in driving resistance.

Researchers from the University of Oxford in the United Kingdom, Hospital Universitario Ramon y Cajal in Spain, and Institut Pasteur in France conducted a recent study on how plasmids affect gene evolution in Escherichia coli. In their paper, which was recently published in the journal, Nature Ecology & Evolution, the authors note previous findings on how plasmids aid in horizontal gene transfer between bacteria, such as in the case of the plasmid-mediated gene mcr-1. Health officials have found the gene that creates resistance to the antibiotic colistin in strains of E. coli and are increasingly concerned due to its ability to spread resistance between bacterial species. “Many of the most important resistance genes are found on plasmids, which are small, circular DNA molecules that live inside bacteria,” explained study author R. Craig MacLean in a recent press release from the University of Oxford. “Plasmids are capable of moving between bacteria and are usually thought of as being important ‘vehicles’ that transfer resistance genes between bacteria.”

The new study looked at how plasmids act as catalysts of gene evolution, with the researchers constructing an experimental model using E.coli strains carrying the beta-lactam resistance gene blaTEM-1 on both the chromosomes and the plasmids of the bacteria. When the strains were exposed to increasing concentrations of the antibiotic ceftazidime, the research team noted that the plasmids acted to speed up resistance development by increasing the rate of novel mutations and heightening the mutations’ effects.

“Our paper demonstrates that plasmids can also act as evolutionary catalysts that accelerate the evolution of new forms of resistance,” explained Dr. MacLean. “This occurs because bacteria usually carry more than one copy of a plasmid, which allows resistance genes carried by plasmids to rapidly evolve new functions — in this case, the ability to degrade an antibiotic. Additionally, plasmids automatically amplify the number of copies of these new and improved resistance genes.”

According to the authors, their results prove that plasmids go well beyond mediating horizontal gene transfer to give pathogens an evolutionary advantage. “In the short term, carrying blaTEM-1 on a multicopy plasmid (pBGT) is associated with an increase in fitness under conditions of strong selection for β-lactam resistance,” the authors explained in their paper. “In the long term, plasmid pBGT acts as an evolutionary catalyst that facilitates the evolution of novel variants of blaTEM-1 and allows bacterial populations to evolve clinically relevant levels of ceftazidime resistance.” In demonstrating this new role for plasmids in accelerating antibiotic resistance, the authors say that they’ve highlighted the threat plasmids pose to public health.