Winter Macaulay, Vos Michiel, Buckling Angus, Johnsen Pål Jarle, Harms Klaus
European Centre for Environment and Human Health, University of Exeter Medical School, Penryn Campus, Exeter TR10 9FE, UK.
Environment and Sustainability Institute, University of Exeter, Penryn Campus, Penryn TR10 9FE, UK.
Access Microbiol. 2024 Jul 10;6(7). doi: 10.1099/acmi.0.000733.v4. eCollection 2024.
Natural transformation is the ability of a bacterial cell to take up extracellular DNA which is subsequently available for recombination into the chromosome (or maintenance as an extrachromosomal element). Like other mechanisms of horizontal gene transfer, natural transformation is a significant driver for the dissemination of antimicrobial resistance. Recent studies have shown that many pharmaceutical compounds such as antidepressants and anti-inflammatory drugs can upregulate transformation frequency in the model species . Chemotherapeutic compounds have been shown to increase the abundance of antimicrobial resistance genes and increase colonization rates of potentially pathogenic bacteria in patient gastrointestinal tracts, indicating an increased risk of infection and providing a pool of pathogenicity or resistance genes for transformable commensal bacteria. We here test for the effect of six cancer chemotherapeutic compounds on natural transformation frequency, finding two compounds, docetaxel and daunorubicin, to significantly decrease transformation frequency, and daunorubicin to also decrease growth rate significantly. Enhancing our understanding of the effect of chemotherapeutic compounds on the frequency of natural transformation could aid in preventing the horizontal spread of antimicrobial resistance genes.
自然转化是指细菌细胞摄取细胞外DNA的能力,这些DNA随后可用于重组到染色体中(或作为染色体外元件维持)。与其他水平基因转移机制一样,自然转化是抗菌药物耐药性传播的重要驱动因素。最近的研究表明,许多药物化合物,如抗抑郁药和抗炎药,可上调模式生物中的转化频率。化疗化合物已被证明可增加抗菌药物耐药基因的丰度,并增加患者胃肠道中潜在致病细菌的定植率,这表明感染风险增加,并为可转化的共生细菌提供了致病性或耐药基因库。我们在此测试六种癌症化疗化合物对自然转化频率的影响,发现多西他赛和柔红霉素这两种化合物可显著降低转化频率,且柔红霉素还可显著降低生长速率。加强我们对化疗化合物对自然转化频率影响的理解,有助于预防抗菌药物耐药基因的水平传播。