Suprenant Mark P, Ching Carly, Gross Neila, Sutradhar Indorica, Anderson Jessica E, El Sherif Nourhan, Zaman Muhammad H
Department of Biomedical Engineering, Boston University, Boston, MA, United States.
Department of Materials Science and Engineering, Boston University, Boston, MA, United States.
Front Microbiol. 2024 Dec 9;15:1491532. doi: 10.3389/fmicb.2024.1491532. eCollection 2024.
Antimicrobial resistance (AMR) is a global health crisis that is predicted to worsen in the coming years. While improper antibiotic usage is an established driver, less is known about the impact of other endogenous and exogeneous environmental factors, such as metals, on AMR. One metal of interest is zinc as it is often used as a supplement for diarrhea treatment prior to antibiotics.
Here, we probed the impact of zinc on ciprofloxacin resistance in via altering zinc exposure time and order. We found that the order of exposure to zinc impacted resistance development. These impacted samples then underwent whole genome and RNA sequencing analysis.
Zinc pre-exposure led to a subsequent acceleration of ciprofloxacin resistance. Specifically, we saw that 5 days of zinc pre-exposure led samples to have nearly a 4× and 3× higher MIC after 2 and 3 days of subinhibitory antibiotics, respectively, compared to samples not pre-exposed to zinc, but only if ciprofloxacin exposure happened in the absence of zinc. Additionally, for samples that underwent the same pre-exposure treatment, those exposed to a combination of zinc and ciprofloxacin saw delayed ciprofloxacin resistance compared to those exposed to only ciprofloxacin resulting in up to a 5× lower MIC within the first 2 days of antibiotic exposure. We did not observe any genetic changes or changes in antibiotic tolerance in cells after zinc pre-exposure, suggesting changes in gene expression may underlie these phenotypes.
These results highlight the need to reexamine the role of zinc, and supplements more broadly, on antibiotic resistance evolution.
抗菌药物耐药性（AMR）是一场全球健康危机，预计在未来几年会恶化。虽然不当使用抗生素是一个公认的驱动因素，但对于其他内源性和外源性环境因素（如金属）对AMR的影响了解较少。一种受关注的金属是锌，因为它常用于在使用抗生素之前治疗腹泻。
在此，我们通过改变锌暴露时间和顺序，探究了锌对环丙沙星耐药性的影响。我们发现锌的暴露顺序会影响耐药性的发展。然后对这些受影响的样本进行全基因组和RNA测序分析。
预先暴露于锌会导致随后环丙沙星耐药性加速。具体而言，我们发现，与未预先暴露于锌的样本相比，预先暴露于锌5天的样本在亚抑菌浓度抗生素处理2天和3天后，其最低抑菌浓度（MIC）分别高出近4倍和3倍，但前提是环丙沙星暴露发生在无锌的情况下。此外，对于接受相同预先暴露处理的样本，与仅暴露于环丙沙星的样本相比，暴露于锌和环丙沙星组合的样本的环丙沙星耐药性出现延迟，在抗生素暴露的头2天内MIC降低多达5倍。我们在锌预先暴露后的细胞中未观察到任何基因变化或抗生素耐受性变化，这表明基因表达的变化可能是这些表型的基础。
这些结果凸显了重新审视锌以及更广泛的补充剂对抗生素耐药性演变的作用的必要性。
