Abstract：
IncX3 plasmids carrying the New Delhi metallo-β-lactamase-encoding gene, blaNDM-5, are rapidly spreading globally in both humans and animals. Given that carbapenems are listed on the WHO AWaRe watch group and are prohibited for use in animals, the drivers for the successful dissemination of Carbapenem-Resistant Enterobacterales (CRE) carrying blaNDM-5-IncX3 plasmids still remain unknown. We observe that E. coli carrying blaNDM-5-IncX3 can persist in chicken intestines either under the administration of amoxicillin, one of the largest veterinary β-lactams used in livestock, or without any antibiotic pressure. We therefore characterise the blaNDM-5-IncX3 plasmid and identify a transcription regulator, VirBR, that binds to the promoter of the regulator gene actX enhancing the transcription of Type IV secretion systems (T4SS); thereby, promoting conjugation of IncX3 plasmids, increasing pili adhesion capacity and enhancing the colonisation of blaNDM-5-IncX3 transconjugants in animal digestive tracts. Our mechanistic and in-vivo studies identify VirBR as a major factor in the successful spread of blaNDM-5-IncX3 across one-health AMR sectors. Furthermore, VirBR enhances the plasmid conjugation and T4SS expression by the presence of copper and zinc ions, thereby having profound ramifications on the use of universal animal feeds.
摘要：
携带新德里金属β-内酰胺酶编码基因的IncX3质粒，blaNDM-5在人类和动物中迅速传播。鉴于碳青霉烯被列入WHOAWaRe观察小组，禁止在动物中使用，携带blaNDM-5-IncX3质粒的耐碳青霉烯类肠杆菌(CRE)成功传播的驱动因素仍然未知.我们观察到携带blaNDM-5-IncX3的大肠杆菌可以在阿莫西林给药的情况下在鸡肠中持续存在，用于牲畜的最大的兽用β-内酰胺之一，或者没有任何抗生素压力。因此，我们表征了blaNDM-5-IncX3质粒并鉴定了转录调节因子，VirBR,与调节基因actX的启动子结合，增强IV型分泌系统（T4SS）的转录；从而，促进IncX3质粒的缀合，增加菌毛粘附能力并增强blaNDM-5-IncX3转结合体在动物消化道中的定植。我们的机制和体内研究确定VirBR是blaNDM-5-IncX3在单健康AMR部门成功传播的主要因素。此外，VirBR通过铜和锌离子的存在增强质粒接合和T4SS表达，从而对通用动物饲料的使用产生了深远的影响。
