Effect of chemotherapeutic agents on natural transformation frequency in Acinetobacter baylyi

Macaulay Winter, M. Vos, A. Buckling, Pål J. Johnsen, Klaus Harms
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Abstract

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 Acinetobacter baylyi. 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 A. baylyi 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.
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化疗药物对巴氏不动杆菌自然转化频率的影响
自然转化是指细菌细胞吸收细胞外 DNA 的能力,这些 DNA 随后可重组到染色体中(或作为染色体外元件保持)。与其他横向基因转移机制一样,自然转化也是抗菌药耐药性传播的重要驱动力。最近的研究表明,许多药物化合物(如抗抑郁药和消炎药)可提高模式物种贝氏不动杆菌(Acinetobacter baylyi)的转化频率。化疗化合物已被证明会增加抗菌药耐药性基因的丰度,并增加潜在致病菌在患者胃肠道中的定植率,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性基因库。我们在这里测试了六种癌症化疗化合物对巴氏杀菌杆菌自然转化频率的影响,发现多西他赛和多诺霉素这两种化合物能显著降低转化频率,多诺霉素还能显著降低生长速度。进一步了解化疗化合物对自然转化频率的影响有助于防止抗菌药耐药性基因的水平传播。
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