Fluoroquinolones and cephalosporins are critically important antimicrobial classes for both human and veterinary medicine. We previously found a drastic increase in enrofloxacin resistance in clinical Escherichia coli isolates collected from diseased pigs from the United States over 10 years (2006 to 2016). However, the genetic determinants responsible for this increase have yet to be determined. The aim of the present study was to identify and characterize the genetic basis of resistance against fluoroquinolones (enrofloxacin) and extended-spectrum cephalosporins (ceftiofur) in swine E. coli isolates using whole-genome sequencing (WGS). bla_CMY-2 (carried by IncA/C2, IncI1, and IncI2 plasmids), bla_CTX-M (carried by IncF, IncHI2, and IncN plasmids), and bla_SHV-12 (carried by IncHI2 plasmids) genes were present in 87 (82.1%), 19 (17.9%), and 3 (2.83%) of the 106 ceftiofur-resistant isolates, respectively. Of the 110 enrofloxacin-resistant isolates, 90 (81.8%) had chromosomal mutations in gyrA, gyrB, parA, and parC genes. Plasmid-mediated quinolone resistance genes [qnrB77, qnrB2, qnrS1, qnrS2, and aac-(6)-lb′-cr] borne on ColE, IncQ2, IncN, IncF, and IncHI2 plasmids were present in 24 (21.8%) of the enrofloxacin-resistant isolates. Virulent IncF plasmids present in swine E. coli isolates were highly similar to epidemic plasmids identified globally. High-risk E. coli clones, such as ST744, ST457, ST131, ST69, ST10, ST73, ST410, ST12, ST127, ST167, ST58, ST88, ST617, ST23, etc., were also found in the U.S. swine population. Additionally, the colistin resistance gene (mcr-9) was present in several isolates. This study adds valuable information regarding resistance to critical antimicrobials with implications for both animal and human health.

中文翻译：

---

美国病猪分离出的大肠杆菌对超广谱头孢菌素和氟喹诺酮类耐药的遗传决定因素

氟喹诺酮类和头孢菌素类是人类医学和兽医学中极为重要的抗菌药物类别。我们之前发现10 年（2006 年至 2016 年）从美国患病猪收集的临床大肠杆菌分离株中恩诺沙星耐药性急剧增加。然而，导致这种增加的遗传决定因素尚未确定。本研究的目的是使用全基因组测序 (WGS)鉴定和表征猪大肠杆菌分离株对氟喹诺酮类（恩诺沙星）和超广谱头孢菌素（头孢噻呋）的耐药性的遗传基础。bla _CMY-2（由 IncA/C2、IncI1 和 IncI2 质粒携带）、bla _CTX-M（由 IncF、IncHI2 和 IncN 质粒携带）和bla _SHV-12（由 IncHI2 质粒携带）基因存在于 106 个头孢噻呋-分别为耐药菌株。在 110 株恩诺沙星耐药株中，90 株 (81.8%) 在gyrA、gyrB、parA和parC基因中有染色体突变。质粒介导的喹诺酮抗性基因 [ qnrB77、qnrB2、qnrS1、qnrS2和aac-(6)-lb'-cr] 携带 CoE、IncQ2、IncN、IncF 和 IncHI2 质粒的菌株存在于 24 种 (21.8%) 的恩诺沙星耐药菌株中。猪大肠杆菌分离株中存在的毒性 IncF 质粒与全球鉴定的流行质粒高度相似。在美国猪群中也发现了高危大肠杆菌克隆，如 ST744、ST457、ST131、ST69、ST10、ST73、ST410、ST12、ST127、ST167、ST58、ST88、ST617、ST23 等。此外，在几个分离株中存在粘菌素抗性基因 ( mcr-9 )。这项研究增加了有关对关键抗菌素的耐药性的宝贵信息，这些信息对动物和人类健康都有影响。