摘要
      细菌的抗微生物耐药性对人类和动物健康都是一种威胁。我们旨在了解驯化和抗菌治疗对马肠道微生物组中耐药细菌、抗生素耐药基因（ARGs）和1类整合子（C1I）的类型和数量的影响。从野马、健康的农场马和接受兽医治疗的马中分离出抗生素耐药性的粪便细菌，并通过PCR对分离物（9083个菌落）进行C1I筛选；这些频率分别为9.8%（兽医马）、0.31%（农场马）和0.05%（野马）。对71个独特的C1I+分离株（17个放线菌属和54个变形菌属）进行耐药性分析和基因组测序。农场马主要产C1I+放线菌（红球菌、微球菌、微杆菌、关节杆菌、谷氨酸杆菌、柯库氏菌），而兽医马主要产C1 I+变形菌（埃希氏菌、克雷伯菌、肠杆菌、泛球菌、不动杆菌、勒克莱尔菌、Ochrobactrum）；vet分离株在C1Is中具有更广泛的抗性和更强的PC启动子。放线菌中的所有整合子两侧都有IS6100的拷贝，微球菌除外，其中一种新的IS5家族元件（ISMcte1）与动员有关。在变形杆菌中，C1Is主要与IS26、IS1、Tn21、Tn1721、Tn 512和一种假定的耐甲醛转座子（Tn7489）有关。检索到几个含有C1I的大型质粒重叠群；其中两种（质粒类型Y和F）也具有广泛的金属抗性基因，包括一种新的铜抗性转座子（Tn7519）。兽医处理和驯化都会增加马肠道微生物群中C1Is的频率，而这些人为因素中的每一个都会选择一组不同的含整合素的细菌。
重要性人们越来越认识到，需要采取“一个健康”的方法来解决日益严重的抗微生物耐药性问题。这要求不仅从人类医学的角度来研究这个问题，还包括考虑抗菌药物在兽医和农业中的作用，并认识到其他生态区在ARGs和C1I等流动遗传元素传播中的重要性。我们已经表明，驯化和兽医治疗增加了马肠道微生物群中C1I的发生频率，在健康的农场马中，在放线菌中意外发现了C1I，而在接受抗微生物兽医治疗的马中，发生了分类转变，发现了更典型的含整合子的变形菌。我们在含有整合子的马细菌的基因组重叠群上鉴定了几种新的可移动遗传元件（质粒、插入序列[IS]和转座子）。
ABSTRACT
Antimicrobial resistance in bacteria is a threat to both human and animal health. We aimed to understand the impact of domestication and antimicrobial treatment on the types and numbers of resistant bacteria, antibiotic resistance genes (ARGs), and class 1 integrons (C1I) in the equine gut microbiome. Antibiotic-resistant fecal bacteria were isolated from wild horses, healthy farm horses, and horses undergoing veterinary treatment, and isolates (9,083 colonies) were screened by PCR for C1I; these were found at frequencies of 9.8% (vet horses), 0.31% (farm horses), and 0.05% (wild horses). A collection of 71 unique C1I+ isolates (17 Actinobacteria and 54 Proteobacteria) was subjected to resistance profiling and genome sequencing. Farm horses yielded mostly C1I+ Actinobacteria (Rhodococcus, Micrococcus, Microbacterium, Arthrobacter, Glutamicibacter, Kocuria), while vet horses primarily yielded C1I+ Proteobacteria (Escherichia, Klebsiella, Enterobacter, Pantoea, Acinetobacter, Leclercia, Ochrobactrum); the vet isolates had more extensive resistance and stronger PC promoters in the C1Is. All integrons in Actinobacteria were flanked by copies of IS6100, except in Micrococcus, where a novel IS5 family element (ISMcte1) was implicated in mobilization. In the Proteobacteria, C1Is were predominantly associated with IS26 and also IS1, Tn21, Tn1721, Tn512, and a putative formaldehyde-resistance transposon (Tn7489). Several large C1I-containing plasmid contigs were retrieved; two of these (plasmid types Y and F) also had extensive sets of metal resistance genes, including a novel copper-resistance transposon (Tn7519). Both veterinary treatment and domestication increase the frequency of C1Is in equine gut microflora, and each of these anthropogenic factors selects for a distinct group of integron-containing bacteria.
IMPORTANCE There is increasing acknowledgment that a “one health” approach is required to tackle the growing problem of antimicrobial resistance. This requires that the issue is examined from not only the perspective of human medicine but also includes consideration of the roles of antimicrobials in veterinary medicine and agriculture and recognizes the importance of other ecological compartments in the dissemination of ARGs and mobile genetic elements such as C1I. We have shown that domestication and veterinary treatment increase the frequency of occurrence of C1Is in the equine gut microflora and that, in healthy farm horses, the C1I are unexpectedly found in Actinobacteria, while in horses receiving antimicrobial veterinary treatments, a taxonomic shift occurs, and the more typical integron-containing Proteobacteria are found. We identified several new mobile genetic elements (plasmids, insertion sequences [IS], and transposons) on genomic contigs from the integron-containing equine bacteria.

https://journals.asm.org/doi/abs/10.1128/aem.01590-22?casa_token=XqAoh64fKwkAAAAA:o61Cj32IGgNJ7rFibdgU1f5tMvZvD7QDj8lSUXK0q7ecCGSKBIlmjC9hCEZxnOZaS2VcWlaV3_8cxhM