摘要
      食用动物是已知的耐多药（MDR）大肠杆菌的宿主，但缺乏关于影响这些生物定殖的因素的信息。在此，我们报道了来自非冗余小牛粪便样本的66个耐多药大肠杆菌分离株的基因组分析。对氨基糖苷类、β-内酰胺类、磺酰胺类和四环素类产生耐药性的基因是检测到的最常见的抗微生物耐药性基因（ARGs），包括对具有临床意义的抗生素（blaCMY-2、blaCTX-M、mph（A）、erm（B）、aac（6'）Ib-cr和qnrS1）产生耐药性的那些基因。共现分析表明，多个ARGs显著地相互共现，并与金属和杀生物剂抗性基因（MRGs和BRGs）显著共现。基因组分析还表明，从小牛身上分离的耐多药大肠杆菌具有高度的多样性。最常见的基因型是门群A-ST Cplx 10。高比例的分离株（50%）被鉴定为肠外感染（ExPECs）的病原体序列类型，如ST69、ST410、ST117、ST88、ST617、ST648、ST10、ST58和ST167，并且这些分离株中有相当数量的分离株编码参与人类尿路定植和感染的毒力因子。耐多药菌株和易感菌株在多种副毒力因子（VFs）的存在方面存在显著差异。与肠出血性感染相关的VFs，如stx、tir和eae，更有可能由抗微生物敏感菌株携带，而与肠外感染相关的因素，如sit系统、需氧菌素和pap菌毛基因，更有可能编码在耐药菌株中。对菌株之间SNPs的比较分析表明，从不同农场的动物身上回收了几种密切相关的菌株，这表明抗性菌株有可能在农场之间传播。这些结果表明，小牛是多种耐多药大肠杆菌的宿主，这些大肠杆菌携带与人类感染相关的各种抗性基因和毒力因子。ARGs与MRGs、BRGs和铁清除基因（sit和需氧菌素）共存的证据可能导致减少耐药细菌在小牛肠道定植的管理策略。
Abstract
Food animals are known reservoirs of multidrug-resistant (MDR) Escherichia coli, but information regarding the factors influencing colonization by these organisms is lacking. Here we report the genomic analysis of 66 MDR E. coli isolates from non-redundant veal calf fecal samples. Genes conferring resistance to aminoglycosides, β-lactams, sulfonamides, and tetracyclines were the most frequent antimicrobial resistance genes (ARGs) detected and included those that confer resistance to clinically significant antibiotics (blaCMY-2, blaCTX-M, mph(A), erm(B), aac(6’)Ib-cr, and qnrS1). Co-occurrence analyses indicated that multiple ARGs significantly co-occurred with each other, and with metal and biocide resistance genes (MRGs and BRGs). Genomic analysis also indicated that the MDR E. coli isolated from veal calves were highly diverse. The most frequently detected genotype was phylogroup A-ST Cplx 10. A high percentage of isolates (50%) were identified as sequence types that are the causative agents of extra-intestinal infections (ExPECs), such as ST69, ST410, ST117, ST88, ST617, ST648, ST10, ST58, and ST167, and an appreciable number of these isolates encoded virulence factors involved in the colonization and infection of the human urinary tract. There was a significant difference in the presence of multiple accessory virulence factors (VFs) between MDR and susceptible strains. VFs associated with enterohemorrhagic infections, such as stx, tir, and eae, were more likely to be harbored by antimicrobial-susceptible strains, while factors associated with extraintestinal infections such as the sit system, aerobactin, and pap fimbriae genes were more likely to be encoded in resistant strains. A comparative analysis of SNPs between strains indicated that several closely related strains were recovered from animals on different farms indicating the potential for resistant strains to circulate among farms. These results indicate that veal calves are a reservoir for a diverse group of MDR E. coli that harbor various resistance genes and virulence factors associated with human infections. Evidence of co-occurrence of ARGs with MRGs, BRGs, and iron-scavenging genes (sit and aerobactin) may lead to management strategies for reducing colonization of resistant bacteria in the calf gut.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265445