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Researchers at Uppsala University have identified two newly discovered mechanisms in bacteria that contribute to the rapid development of antibiotic resistance. Published in Nature Communications, the study highlights how changes in the number of copies of resistance genes in bacteria can swiftly increase antibiotic resistance, posing a significant challenge to current treatments.
The research focused on heteroresistance, a phenomenon where the majority of bacteria in a population are sensitive to antibiotics, but a very small subpopulation exhibits heightened resistance. This resistant subgroup, typically around 1 in 100,000 bacteria, can continue to grow despite antibiotic treatment, making infections harder to treat and potentially accelerating the spread of antibiotic resistance.
Helen Wang, the last author of the study, explains the significance of the findings: “It was completely unknown until now that these mechanisms could promote heteroresistance. 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.”
A critical aspect of the study was the role of plasmids in spreading resistance genes among bacteria. Plasmids are small, free-standing DNA rings that bacteria use to store genes outside their chromosomes. The researchers discovered two new mechanisms where the number of copies of plasmids carrying resistance genes can increase up to 90 times. These mechanisms, along with a third known mechanism involving gene amplification, can operate independently yet simultaneously within the same bacterial cell.
Hervé Nicoloff, the study’s first author, elaborates on the complexity of heteroresistance: “Heteroresistance involving an increased number of copies of resistance genes is much more complex than previously thought. Bacteria can actually use three different mechanisms, all of which can occur in parallel in the same bacterium, to temporarily increase the number of copies of resistance genes and thereby generate antibiotic resistance.”
One of the challenges in detecting these resistant bacteria is their instability. All three mechanisms can quickly revert to sensitivity when antibiotics are not present, making it difficult to identify resistant bacteria during clinical examinations. Wang emphasizes the need for improved diagnostic methods: “Given what we now know, it is important to be able to develop better diagnostic methods that can detect increased antibiotic resistance.”
The study underscores the urgency of understanding and addressing heteroresistance to enhance the effectiveness of antibiotic treatments and combat the growing threat of antibiotic-resistant bacteria.
