Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA.
Équipe Pathogènes Hydriques Santé Environnements, UMR 5569 HSM, Université de Montpellier, Montpellier, France.
mBio. 2018 Jul 24;9(4):e01328-18. doi: 10.1128/mBio.01328-18.
Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont , a puzzling rise in Cp-resistant (Cp) infections has been reported. We report on the effects of subtherapeutic FQ concentrations on bacteria in an environmental reservoir, the medicinal leech, and describe the presence of multiple antibiotic resistance mutations and a gain-of-function resistance gene. We link the rise of Cp isolates to exposure of the leech microbiota to very low levels of Cp (0.01 to 0.04 µg/ml), <1/100 of the clinical resistance breakpoint for Using competition experiments and comparative genomics of 37 strains, we determined the mechanisms of resistance in clinical and leech-derived isolates, traced their origin, and determined that the presence of merely 0.01 µg/ml Cp provides a strong competitive advantage for Cp strains. Deep-sequencing the Cp-conferring region of enabled tracing of the mutation-harboring population in archived gut samples, and an increase in the frequency of the Cp-conferring mutation in 2011 coincides with the initial reports of Cp infections in patients receiving leech therapy. The role of subtherapeutic antimicrobial contamination in selecting for resistant strains has received increasing attention and is an important clinical matter. This study describes the relationship of resistant bacteria from the medicinal leech, , with patient infections following leech therapy. While our results highlight the need for alternative antibiotic therapies, the rise of Cp bacteria demonstrates the importance of restricting the exposure of animals to antibiotics approved for veterinary use. The shift to a more resistant community and the dispersion of Cp-conferring mechanisms via mobile elements occurred in a natural setting due to the presence of very low levels of fluoroquinolones, revealing the challenges of controlling the spread of antibiotic-resistant bacteria and highlighting the importance of a holistic approach in the management of antibiotic use.
氟喹诺酮类（FQs）和环丙沙星（Cp）是痕量污染环境的重要抗菌药物。尽管 Cp 已被推荐用于接受水蛭疗法的患者作为预防措施，以防止水蛭肠道共生菌感染，但据报道 Cp 耐药（Cp）感染却令人费解地上升。我们报告了亚治疗浓度的 FQ 对环境储层（药用蛭）中细菌的影响，并描述了多种抗生素耐药突变和功能获得性耐药基因的存在。我们将 Cp 分离株的上升与暴露于极低水平的 Cp（0.01 至 0.04 µg/ml）有关联，<1/100 的临床耐药折点 利用竞争实验和 37 株的比较基因组学，我们确定了临床和来源于水蛭的分离株的耐药机制，追踪了它们的起源，并确定仅仅 0.01 µg/ml 的 Cp 就为 Cp 菌株提供了强大的竞争优势。对赋予 Cp 能力的区域进行深度测序，使我们能够追踪存档肠道样本中携带突变的 种群，并在 2011 年，赋予 Cp 能力的突变频率增加与接受水蛭疗法的患者中首次报道 Cp 感染相吻合。在选择耐药菌株方面，亚治疗性抗菌药物污染的作用受到越来越多的关注，这也是一个重要的临床问题。本研究描述了药用蛭中的耐药细菌与接受水蛭疗法后的患者感染之间的关系。虽然我们的研究结果强调了需要替代抗生素疗法，但 Cp 细菌的出现突显了限制批准用于兽医的抗生素暴露于动物的重要性。由于存在非常低水平的氟喹诺酮类药物，耐氟喹诺酮类社区的转变和 Cp 赋予机制通过移动元件的传播在自然环境中发生，这揭示了控制抗生素耐药细菌传播的挑战，并强调了在抗生素使用管理中采取整体方法的重要性。
