Significant Increase in Antibiotic Resistance Genes Found in Humans and Livestock

Biomedical engineers at Duke University have discovered a significant connection between the dissemination of antibiotic resistance genes and the development of resistance to new drugs in specific pathogens.

The research demonstrates that bacteria exposed to elevated levels of antibiotics frequently possess numerous identical copies of protective antibiotic resistance genes. These duplicated resistance genes are often associated with “jumping genes” known as transposons, which can transfer between strains. This mechanism not only facilitates the spread of resistance but also provides a platform for evolutionary processes to generate resistance to new classes of drugs.

The findings were published in the journal Nature Communications.

Previous research from the Lingchong You lab indicated that 25% of bacterial pathogens can disseminate antibiotic resistance through horizontal gene transfer. They also demonstrated that the presence of antibiotics does not accelerate the rate of horizontal gene transfer, suggesting that other factors drive the spread of these genes.

Bacteria are constantly evolving under many pressures, and elevated duplication of certain genes is like a fingerprint left at the crime scene that allows us to see what kinds of functions are evolving really rapidly. We hypothesized that bacteria under attack from antibiotics would often have multiple copies of protective resistance genes, but until recently we didn’t have the technology to find the smoking gun.”

Rohan Maddamsetti, Postdoctoral Fellow, Duke University Pratt School of Engineering

Rohan Maddamsetti works in the laboratory of Lingchong You, the James L. Meriam Distinguished Professor of Biomedical Engineering at Duke

Traditional DNA-reading methods involve copying short snippets of genes and tallying them, which can make it challenging to discern whether high counts of specific sequences are genuinely present in the sample or if they are artificially amplified during the reading process. However, in the last five years, complete genome sequencing using long-read technology has become more prevalent. This advancement enables researchers to identify high levels of genetic repetition with greater accuracy.

In their study, Maddamsetti and colleagues quantified the repetitions of resistance genes in samples of bacterial pathogens collected from various environments. They found that bacterial pathogens residing in environments with elevated levels of antibiotic use, such as humans and livestock, exhibited an enrichment of multiple identical copies of antibiotic resistance genes. In contrast, such duplications were rare in bacteria found in wild plants, animals, soil, and water.

“Most bacteria have some basic antibiotic resistance genes in them, but we rarely saw them being duplicated out in nature. By contrast, we saw lots of duplication happening in humans and livestock where we’re likely hammering them with antibiotics,” You stated.

Additionally, the researchers discovered that the levels of resistance duplication were even greater in samples obtained from clinical datasets, where patients are likely to undergo antibiotic treatment. This observation is crucial, as the escalation in copying antibiotic resistance genes also heightens the probability of bacteria evolving resistance to new forms of treatments.

Constantly creating copies of genes for resistance to penicillin, for example, may be the first step toward being able to break down a new kind of drug. It gives evolution more rolls of the dice to find a special mutation.”

Rohan Maddamsetti, Postdoctoral Fellow, Duke University Pratt School of Engineering

You adds, “Everyone recognizes there is a growing antibiotic resistance crisis, and the knee-jerk reaction is to develop new antibiotics. But what we find time and again is that, if we can figure out how to use antibiotics more efficiently and effectively, we can potentially address this crisis much more effectively than simply developing new drugs.”

“The majority of antibiotics used in the United States are not used on patients, they’re used in agriculture,” You noted. “So this is an especially important message for the livestock industry, which is a major driver of why antibiotic resistance is always out there and becoming more serious.”