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  • The Role of Gene Duplication in the Spread and Evolution of Antibiotic Resistance

    In a recent study conducted by biomedical engineers at Duke University, a significant connection has been established between the proliferation of antibiotic resistance genes and the emergence of resistance to newer drugs in certain bacteria. Published in Nature Communications, this research provides a deeper understanding of how bacteria adapt to resist antibiotics, highlighting the role of gene duplication and transposons in this process.

    The study, led by postdoctoral fellow Rohan Maddamsetti in the laboratory of Lingchong You, the James L. Meriam Distinguished Professor of Biomedical Engineering at Duke, focused on the genetic mechanisms that facilitate the spread of antibiotic resistance. The researchers discovered that bacteria subjected to high levels of antibiotics tend to have multiple identical copies of antibiotic resistance genes. These genes are often associated with transposons, or "jumping genes," which can move between different strains of bacteria, facilitating the spread of resistance.

    Maddamsetti commented on the significance of their findings, stating, "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." This analogy underscores the detective-like approach the researchers took to uncover the mechanisms behind antibiotic resistance.

    The Duke University team employed advanced long-read genome sequencing technologies, which have become more prevalent in the past five years, to accurately identify repeated genetic sequences within bacterial genomes. This method overcomes the limitations of traditional DNA-reading technology, which can mistakenly amplify specific sequences, obscuring the true genetic composition of a sample.

    Their investigation revealed that bacteria from environments with high antibiotic usage, such as human and livestock populations, had a higher incidence of duplicated antibiotic resistance genes. In contrast, such genetic duplications were infrequent in bacteria isolated from wild plants, animals, soil, and water. Lingchong You highlighted the impact of antibiotic usage, noting, "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."

    Furthermore, the study found even greater levels of resistance gene duplication in clinical samples from patients undergoing antibiotic treatment. This suggests that the amplification of antibiotic resistance genes not only contributes to the spread of existing resistance but also enhances the potential for bacteria to develop resistance to new drugs.

    Addressing the broader implications of their findings, You emphasized the importance of efficient antibiotic usage, particularly in the agricultural sector, where the majority of antibiotics in the United States are used. "Everyone recognizes there is a growing antibiotic resistance crisis, and the knee-jerk reaction is to develop new antibiotics," You said. "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."

    This research sheds light on the genetic strategies employed by bacteria to resist antibiotics, underscoring the need for more judicious use of these drugs in both medical and agricultural settings. By understanding the mechanisms behind antibiotic resistance, scientists and policymakers can develop more effective strategies to combat this escalating health crisis.

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