Emory Antibiotic Resistance Center, Atlanta, Georgia, USA.
Emory Vaccine Center, Atlanta, Georgia, USA.
mBio. 2021 Jan 19;12(1):e02994-20. doi: 10.1128/mBio.02994-20.
The increasing frequency of antibiotic resistance poses myriad challenges to modern medicine. Environmental survival of multidrug-resistant bacteria in health care facilities, including hospitals, creates reservoirs for transmission of these difficult to treat pathogens. To prevent bacterial colonization, these facilities deploy an array of infection control measures, including bactericidal metals on surfaces, as well as implanted devices. Although antibiotics are routinely used in these health care environments, it is unknown whether and how antibiotic exposure affects metal resistance. We identified a multidrug-resistant clinical isolate that displayed heteroresistance to the antibiotic colistin, where only a minor fraction of cells within the population resist the drug. When this isolate was grown in the presence of colistin, a 9-kb DNA region was duplicated in the surviving resistant subpopulation, but surprisingly, was not required for colistin heteroresistance. Instead, the amplified region included a three-gene locus () that conferred resistance to the bactericidal metal, nickel. expression alone was sufficient to confer nickel resistance to K-12. Due to its selection for the colistin-resistant subpopulation harboring the duplicated 9-kb region that includes , colistin treatment led to enhanced nickel resistance. Taken together, these data suggest that the use of antibiotics may inadvertently promote enhanced resistance to antimicrobial metals, with potentially profound implications for bacterial colonization and transmission in the health care environment. To inhibit bacterial transmission and infection, health care facilities use bactericidal metal coatings to prevent colonization of surfaces and implanted devices. In these environments, antibiotics are commonly used, but their effect on metal resistance is unclear. The data described here reveal that exposure of a human isolate of to a last-line antibiotic, colistin, resulted in a DNA amplification that does not confer antibiotic resistance but instead facilitates resistance to the toxic metal nickel. This highlights a novel aspect of antibiotic and metal interplay. Concerningly, these data suggest the use of antibiotics could in some cases promote bacterial survival and colonization in the health care environment and ultimately increase transmission and infection of patients.
抗生素耐药性的频率不断增加，给现代医学带来了无数挑战。在医疗机构（包括医院）中，耐多药细菌在环境中的生存能力导致这些难以治疗的病原体传播的储库。为了防止细菌定植，这些设施部署了一系列感染控制措施，包括表面的杀菌金属以及植入物。尽管抗生素在这些医疗环境中经常使用，但尚不清楚抗生素暴露是否以及如何影响金属耐药性。我们鉴定了一种多药耐药的临床分离株，该分离株对抗生素粘菌素表现出异质性耐药性，即只有人群中的一小部分细胞对该药物具有耐药性。当该分离株在粘菌素存在下生长时，存活的耐药亚群中复制了一个 9kb 的 DNA 区域，但令人惊讶的是，该区域对于粘菌素异质性耐药性不是必需的。相反，扩增区域包括一个三基因座（），该基因座赋予了对杀菌金属镍的耐药性。 单独表达足以赋予 K-12 对镍的耐药性。由于其选择了携带包含的复制的 9kb 区域的粘菌素耐药亚群，粘菌素处理导致镍耐药性增强。综上所述，这些数据表明，抗生素的使用可能会无意中促进对抗菌金属的增强耐药性，这对医疗机构环境中的细菌定植和传播可能具有深远的影响。为了抑制细菌传播和感染，医疗机构使用杀菌金属涂层来防止表面和植入物的定植。在这些环境中，抗生素通常被使用，但它们对金属耐药性的影响尚不清楚。这里描述的数据表明，暴露于一种人类分离株 到一种最后一线抗生素粘菌素，导致 DNA 扩增，该扩增不赋予抗生素耐药性，但反而促进对有毒金属镍的耐药性。这突出了抗生素和金属相互作用的一个新方面。令人担忧的是，这些数据表明，在某些情况下，抗生素的使用可能会促进医疗机构环境中细菌的存活和定植，并最终增加患者的传播和感染。
