NEW mechanisms in bacteria that contribute to antibiotic resistance by rapidly increasing the number of resistance gene copies have been discovered by researchers at Uppsala University, Uppsala, Sweden. The newly discovered mechanisms promote heteroresistance, a phenomenon in which a small fraction of resistant bacteria in a population (around 1 in 100,000 bacteria) coexist with largely susceptible populations. These small, resistant subpopulations can continue to grow despite antibiotic treatment, posing a significant challenge for the treatment of infectious diseases.
The study elucidates the role of plasmids—small, free-standing DNA rings that bacteria use to store genes outside their chromosomes. The researchers discovered two mechanisms by which the number of plasmids carrying resistance genes can multiply up to 90-fold, significantly increasing bacterial resistance. Along with a third known mechanism involving gene amplification, these processes can occur simultaneously within a bacterium, causing a temporary but complex and rapid increase in antibiotic resistance.
“It was completely unknown until now that these mechanisms could promote heteroresistance,” explained Helen Wang, an author of the study. “Our study shows that they can accelerate the selection and growth of resistant bacteria during antibiotic treatment. This study, which partly involved animals, makes it more relevant to understanding these processes in humans.”
The temporary nature of heteroresistance makes detection challenging during clinical examinations, as resistant bacteria can rapidly revert to susceptibility in the absence of antibiotics. “All three mechanisms are unstable and can quickly revert to sensitivity in the absence of antibiotics,” Wang added. “This makes it more difficult to detect the resistant bacteria during a clinical examination, as they disappear so quickly. Given what we now know, it is important to be able to develop better diagnostic methods that can detect increased antibiotic resistance.”
The study’s insights are pivotal for understanding the role of bacterial resistance in human health, especially as the research involved both laboratory and animal models, enhancing its relevance to clinical settings. By shedding light on these new mechanisms, this research paves the way for improved diagnostic and treatment strategies to combat antibiotic-resistant infections.
Reference
Nicoloff H et al. Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance. Nature Communications. 2024;15(1).
