摘要

用于生物医学研究的非人灵长类动物（NHPs）通常感染志贺氏菌。可引起急性痢疾或慢性发作性腹泻。这些动物经常用喹诺酮类抗生素预防性和临床治疗以根除这些可能的感染。然而，染色体和质粒介导的抗生素耐药性已成为肠杆菌科中物种的新兴关注点。在这项研究中，从三只猕猴的粪便中分离出五种单独的多药耐药福氏志贺菌分离株。抗生素药敏试验证实对氨苄西林，阿莫西林 - 克拉维酸，头孢菌素，庆大霉素，四环素，环丙沙星，恩诺沙星，左氧氟沙星和萘啶酮酸的耐药性降低或易感性降低。福氏志贺菌分离株对甲氧苄氨嘧啶 - 磺胺甲恶唑敏感，并且该药物用于根除两只猕猴的感染。来自所有分离株的质粒DNA对于质粒编码的喹诺酮抗性基因qnrS是阳性的，但对qnrA和qnrB不是。将来自若干福氏志贺菌分离株的质粒DNA缀合和转化为抗生素敏感的大肠杆菌菌株赋予受体对喹诺酮和β-内酰胺的耐药性或降低的易感性。两个代表性福氏志贺氏菌分离株的基因组测序鉴定了质粒样重叠群上的qnrS基因。这些重叠群与先前表征自喹诺酮耐药志贺氏菌福氏志贺氏菌2a和肠道沙门氏菌菌株的质粒序列显示出> 99％的同源性。在这些基因组的染色体和质粒序列中也鉴定出其他抗生素抗性基因和毒力因子基因。这项研究的结果表明猕猴拥有染色体和质粒编码的抗生素抗性基因的致病性福氏志贺菌菌株。据我们所知，这是首次报道质粒介导的喹诺酮类抗生素在从NHPs中分离出来的福氏志贺菌中，并且在预防性或治疗性地用喹诺酮治疗猕猴之前保证肠道病原体的分离和抗生素测试。

Non-human primates (NHPs) for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants isolation and antibiotic testing of enteric pathogens before treating macaques with quinolones prophylactically or therapeutically.

https://www.ncbi.nlm.nih.gov/pubmed/29556221