The arms race between bacteria and antibiotics is nothing new — antimicrobial resistance has been an emerging issue in human and animal health for a long time. But in a new review, NC State researchers used a One Health approach to study the results of whole genome sequencing data and the role of plasmids — small DNA molecules with the ability to pass genes from one bacterial species to another — in the spread of antimicrobial resistance. One Health refers to the concept that the health of the environment, wild and domestic animals, and people are linked.

The Abstract sat down with the review’s authors: Siddhartha Thakur, executive director of the Global One Health Academy and professor of molecular epidemiology; and Daniel Monte, assistant research professor in the College of Veterinary Medicine’s Department of Population Health and Pathobiology, to talk about what plasmids are doing and what – if anything – we can do to stop them.

The Abstract (TA): Whole genome sequencing has revealed that plasmid transfer between different pathogens, like salmonella and E. coli, is a more widespread phenomenon than previously thought. Let’s start with a brief explanation of what a plasmid is and how that transfer occurs.

Thakur and Monte: Plasmids are small, circular DNA molecules that exist separately from a bacterium’s chromosome. Unlike the chromosome, which carries the genes essential for survival, plasmids often carry “extra” genes that can provide important advantages, such as resistance to antibiotics.

One remarkable feature of plasmids is that they can move from one bacterium to another through a process called horizontal gene transfer. You can think of them as portable genetic packages that bacteria are able to exchange, even between different bacterial species, such as salmonella and E. coli. When a plasmid carries an antibiotic resistance gene, that resistance can spread much faster than if it relied only on bacterial reproduction.

Whole genome sequencing has transformed our ability to track these events. Rather than looking only at the bacteria themselves, we can now identify and compare the plasmids they carry, allowing us to follow the movement of resistance genes across humans, animals, foods and the environment. This has fundamentally changed our understanding of how antimicrobial resistance spreads and why a One Health approach is essential.

TA: Does plasmid transfer always confer antimicrobial resistance to the pathogen? Are there instances where there’s been a transfer but no resistance?

Thakur and Monte: No. Plasmid transfer does not always result in antimicrobial resistance. Plasmids are remarkably diverse and can carry many different types of genes. Some carry antibiotic resistance genes, while others carry genes that help bacteria survive in specific environments, produce virulence factors or adapt to different hosts.

What makes certain plasmids particularly concerning is that they can carry several advantageous genes at the same time. For example, a single plasmid may contain genes for antimicrobial resistance, virulence and stress tolerance. When that plasmid is transferred to another bacterium, it can provide multiple survival advantages at once.

Our review focuses on plasmids that carry antimicrobial resistance genes because they play a major role in the global spread of resistance. However, plasmid transfer itself is a natural biological process that has been occurring for millions of years. It only becomes a public health concern when the transferred plasmids carry genes that reduce the effectiveness of antibiotics or otherwise increase the ability of bacteria to cause disease.

TA: What are some of the most concerning examples of plasmid transfer?

Thakur and Monte: Some of the most concerning examples involve plasmids carrying resistance to antibiotics that are considered last-resort treatments for serious infections.

One example is the global spread of plasmids carrying the mcr genes, which confer resistance to colistin, an antibiotic often reserved for infections that no longer respond to other drugs. Another is the spread of plasmids carrying blaNDM, which provides resistance to carbapenems, another critically important class of antibiotics used to treat life-threatening infections.

We are also seeing widespread dissemination of plasmids carrying blaCTX-M genes, which make bacteria resistant to many commonly used cephalosporin antibiotics. These plasmids have been identified in bacteria from food-producing animals, retail meat, humans and the environment, highlighting how resistance can move across interconnected One Health sectors.

Perhaps the most important message is that it is often the plasmids, not the bacteria themselves, that are spreading. The same resistance plasmid can move into different bacterial species, allowing antimicrobial resistance to spread much more rapidly than scientists once appreciated.

TA: How does this impact human and animal health?

Thakur and Monte: Plasmid-mediated antimicrobial resistance affects both human and animal health because it allows resistance genes to spread quickly across different bacteria and environments. As more bacteria acquire these genes, infections become harder to treat, increasing the risk of treatment failure, longer hospital stays and, in some cases, higher mortality.

In food-animal production, resistant bacteria can spread among animals and contaminate meat products or the farm environment. While food safety measures greatly reduce these risks, the food chain remains one of the important pathways through which resistant bacteria and resistance genes can move between animals and people.

Our review highlights that humans, animals, food and the environment are all interconnected. This is why antimicrobial resistance cannot be addressed by focusing on only one sector. Effective surveillance and control require a One Health approach that recognizes these connections and brings together experts in human health, veterinary medicine, food safety and environmental science.

TA: What can we do going forward to prevent plasmid transfer and increased antimicrobial resistance?

Thakur and Monte: There is no single solution, but there are several important steps we can take. First, we need to use antibiotics responsibly in both human and veterinary medicine to reduce the selective pressure that drives the spread of resistance.

Second, we need stronger surveillance. Advances in whole genome sequencing now allow us to track not only resistant bacteria but also the plasmids that carry resistance genes. Detecting these high-risk plasmids early can help us identify emerging threats before they become widespread.

Finally, addressing antimicrobial resistance requires a true One Health approach. Physicians, veterinarians, microbiologists, food producers, environmental scientists and public health professionals all have a role to play. Resistant bacteria and their plasmids do not respect the boundaries between people, animals, food and the environment, so our response cannot be divided by those boundaries either.

The good news is that genomic technologies are giving us powerful new tools to better understand how resistance spreads. By combining these technologies with coordinated surveillance and responsible antimicrobial use, we have a much better opportunity to slow the spread of antimicrobial resistance.

The paper appears in JAC-Antimicrobial Resistance.

This post was originally published in NC State News.