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基因组分析揭示了全球分布的人畜共患病原体 spp. 中与抗生素耐药性相关的遗传决定因素。

Genomic Analysis Reveals the Genetic Determinants Associated With Antibiotic Resistance in the Zoonotic Pathogen spp. Distributed Globally.

作者信息

Rivera-Mendoza Daniel, Martínez-Flores Irma, Santamaría Rosa I, Lozano Luis, Bustamante Víctor H, Pérez-Morales Deyanira

机构信息

Programa de Maestría en Biotecnología, Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico.

Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.

出版信息

Front Microbiol. 2020 Sep 11;11:513070. doi: 10.3389/fmicb.2020.513070. eCollection 2020.

Abstract

The genus groups 32 Gram-negative bacteria species, several being zoonotic pathogens and a major cause of human gastroenteritis worldwide. Antibiotic resistant is considered by the World Health Organization as a high priority pathogen for research and development of new antibiotics. Genetic elements related to antibiotic resistance in the classical and species, which infect humans and livestock, have been analyzed in numerous studies, mainly focused on local geographical areas. However, the presence of these resistance determinants in other species, as well as in and strains distributed globally, remains poorly studied. In this work, we analyzed the occurrence and distribution of antibiotic resistance factors in 237 closed genomes available in NCBI, obtained from isolates collected worldwide, in different dates, from distinct hosts and comprising 22 species. Our data revealed 18 distinct genetic determinants, genes or point mutations in housekeeping genes, associated with resistance to antibiotics from aminoglycosides, β-lactams, fluoroquinolones, lincosamides, macrolides, phenicols or tetracyclines classes, which are differentially distributed among the species tested, on chromosomes or plasmids. Three resistance determinants, the and genes, putatively related to β-lactams resistance, as well as the (AN2) gene, putatively related to lincosamides resistance, had not been reported in ; thus, they represent novel determinants for antibiotic resistance in spp., which expands the insight on the resistome. Interestingly, we found that some of the genetic determinants associated with antibiotic resistance are species-specific; e.g., the gene and the T86V mutation in were found only in the group, whereas genes associated with aminoglycosides resistance were found only in and . Additional analyses revealed how are distributed the resistance and multidrug resistance genotypes assessed, with respect to hosts, geographical locations, and collection dates. Thus, our findings further expand the knowledge on the factors that can determine or favor the antibiotic resistance in species distributed globally, which can be useful to choose a suitable antibiotic treatment to control the zoonotic infections by these bacteria.

摘要

该属包含32种革兰氏阴性细菌,其中几种是人畜共患病原体,也是全球人类肠胃炎的主要病因。世界卫生组织将其抗生素耐药性视为新抗生素研发的高度优先病原体。在众多主要聚焦于局部地理区域的研究中,已对感染人类和牲畜的经典种和种中与抗生素耐药性相关的遗传元件进行了分析。然而,这些耐药决定因素在其他种以及全球分布的种和菌株中的存在情况仍研究不足。在这项工作中,我们分析了从全球收集的不同日期、来自不同宿主且包含22种种的237个种封闭基因组中抗生素耐药因子的发生和分布情况。我们的数据揭示了18种不同的遗传决定因素,即管家基因中的基因或点突变,它们与对氨基糖苷类、β-内酰胺类、氟喹诺酮类、林可酰胺类、大环内酯类、酚类或四环素类抗生素的耐药性相关,这些在受试种、染色体或质粒之间存在差异分布。三种耐药决定因素,即假定与β-内酰胺类耐药性相关的基因和基因,以及假定与林可酰胺类耐药性相关的(AN2)基因,在种中尚未见报道;因此,它们代表了种抗生素耐药性的新决定因素,这扩展了对种耐药组的认识。有趣的是,我们发现一些与抗生素耐药性相关的遗传决定因素是种特异性的;例如,基因和中的T86V突变仅在组中发现,而与氨基糖苷类耐药性相关的基因仅在和中发现。进一步的分析揭示了评估的耐药性和多药耐药性基因型相对于宿主、地理位置和收集日期的分布情况。因此,我们的研究结果进一步扩展了对可决定或促进全球分布的种抗生素耐药性的因素的认识,这有助于选择合适的抗生素治疗来控制这些细菌引起的人畜共患感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e26/7518152/ca5b0be9e7e2/fmicb-11-513070-g001.jpg

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