An In Vitro Chicken Gut Model Demonstrates Transfer of a Multidrug Resistance Plasmid from Salmonella to Commensal Escherichia coli.
An In Vitro Chicken Gut Model Demonstrates Transfer of a Multidrug Resistance Plasmid from Salmonella to Commensal Escherichia coli.
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DOI：
10.1128/mbio.00777-17
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发表时间：
2017-07-18
期刊：
影响因子：
6.4
通讯作者：
Anjum MF
中科院分区：
文献类型：
--
作者：
Card RM;Cawthraw SA;Nunez-Garcia J;Ellis RJ;Kay G;Pallen MJ;Woodward MJ;Anjum MF
鸡的胃肠道中有大量的肠道细菌，这些细菌对宿主发挥着各种有益的作用，包括帮助抵抗病原体的定植。它还可以促进多药耐药（MDR）质粒在大肠杆菌和病原菌之间的接合转移，这是一个重要的公共和动物健康问题，因为它可能影响我们治疗细菌感染的能力。我们使用体外恒化器系统来近似鸡盲肠微生物群，模拟MDR沙门氏菌病原体的定植，并检查其MDR质粒携带多个基因（包括超广谱β-内酰胺酶blaCTX-M1）的转移动力学。我们还评估了头孢噻肟对质粒转移和微生物多样性的影响。通过培养独立的方法获得的细菌群落概况表明，沙门氏菌接种导致细菌群落α多样性和β多样性没有显着变化，而头孢噻肟的管理引起显着改变，这两个措施的多样性，这在很大程度上恢复。从含头孢噻肟的琼脂平板纯化的分离株的PCR和全基因组测序证明了从沙门氏菌到大肠杆菌的MDR质粒转移。即使在不存在头孢噻肟的情况下，也以高速率转移到7种大肠杆菌序列类型，并在3天内分离出耐药菌株。我们的恒化器系统提供了一个很好的代表性的细菌相互作用，包括体内抗生素耐药性转移。它可以作为一种道德和相对便宜的方法来模拟任何动物或人类肠道内抗生素耐药性的传播，并在采用体内研究之前改进减轻其传播的干预措施。抗菌素耐药性的传播对公共卫生和动物健康构成严重威胁，并影响我们应对细菌感染的能力。通过质粒交换转移抗菌素耐药性是特别令人关注的，因为它使不相关的细菌获得耐药性。胃肠道充满了细菌，并为质粒在肠道和病原体之间转移提供了环境。在这里，我们使用鸡肠道微生物群作为范例来模拟细菌感染、抗生素施用和质粒转移的影响。我们表明，转移的多药耐药质粒从人畜共患病原体沙门氏菌到大肠杆菌的发生率很高，即使在没有抗生素管理。我们的工作表明，体外肠道模型提供了一个强大的筛选工具，可用于评估和改进干预措施，在进行动物研究之前减轻肠道中抗生素耐药性的传播。
The chicken gastrointestinal tract is richly populated by commensal bacteria that fulfill various beneficial roles for the host, including helping to resist colonization by pathogens. It can also facilitate the conjugative transfer of multidrug resistance (MDR) plasmids between commensal and pathogenic bacteria which is a significant public and animal health concern as it may affect our ability to treat bacterial infections. We used an in vitro chemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase blaCTX-M1. We also evaluated the impact of cefotaxime administration on plasmid transfer and microbial diversity. Bacterial community profiles obtained by culture-independent methods showed that Salmonella inoculation resulted in no significant changes to bacterial community alpha diversity and beta diversity, whereas administration of cefotaxime caused significant alterations to both measures of diversity, which largely recovered. MDR plasmid transfer from Salmonella to commensal Escherichia coli was demonstrated by PCR and whole-genome sequencing of isolates purified from agar plates containing cefotaxime. Transfer occurred to seven E. coli sequence types at high rates, even in the absence of cefotaxime, with resistant strains isolated within 3 days. Our chemostat system provides a good representation of bacterial interactions, including antibiotic resistance transfer in vivo. It can be used as an ethical and relatively inexpensive approach to model dissemination of antibiotic resistance within the gut of any animal or human and refine interventions that mitigate its spread before employing in vivo studies. The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies.