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PRL2020:抗生素耐药谱及抗生素耐药决定因素的基因组检测

PRL2020: Antibiotic-Resistant Profile and Genomic Detection of Antibiotic Resistance Determinants.

作者信息

Di Pierro Francesco, Campedelli Ilenia, De Marta Patrick, Fracchetti Fabio, Del Casale Antonio, Cavecchia Ilaria, Matera Mariarosaria, Cazzaniga Massimiliano, Bertuccioli Alexander, Guasti Luigina, Zerbinati Nicola

机构信息

Scientific & Research Department, Velleja Research, 20125 Milan, Italy.

Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.

出版信息

Microorganisms. 2023 Jun 24;11(7):1649. doi: 10.3390/microorganisms11071649.

Abstract

Antibiotics are one of the greatest scientific achievements of modern medicine, but excessive use is creating challenges for the future of medicine. Antibiotic resistance (AR) is thought to cause changes in bowel habits and an increased risk of gastroenteritis, but it may also increase the risk of overweight, obesity, autoimmune and atopic diseases, and a low response to vaccines and cancer, likely mediated by antibiotic-induced gut dysbiosis. Probiotic add-on therapy could partially prevent antibiotic-induced gut dysbiosis, but their antibiotic sensitivity features likely limits this potential. The EFSA (European Food Safety Authority) guidelines consider the use of probiotics whose antibiotic-resistant profile could be transferable an important hazard. Recently, a strain of (PRL2020) has shown to be resistant to amoxicillin and amoxicillin-clavulanate (AC) by applying the microdilution protocol according EFSA guidelines. After verifying that horizontal gene transfer is unlikely to take place, this feature suggests its concomitant use with these specific antibiotics. The results of our tests demonstrated that the strain PRL2020 is indeed endowed with amoxicillin- and AC-resistant properties and that it is also insensitive to ampicillin. In-depth analysis of the annotated genome sequence of PRL2020 was employed to query the Comprehensive Antibiotic Resistance Database (CARD) using Resistance Gene Identifier (RGI) software (version 5.2.1). The similarity among the AR determinants found was studied through nucleotide sequence alignment, and it was possible to verify not only the absence of genes explaining these features in the flanking regions but also the presence of genetic sequences ( and ) putatively responsible for rifampicin and erythromycin resistance. Both features are not phenotypically expressed, and for these antibiotics, the strain is within the EFSA limits. Analysis of the flanking regions of these genes revealed possible mobile elements upstream and downstream only in the case of the gene, but the features of the Insertion Sequences (IS) are described as not to cause horizontal transfer. Our findings on strain PRL2020 demonstrate that its AR profile is compatible with antibiotics when taken with the aim of reducing the risk of dysbiosis.

摘要

抗生素是现代医学最伟大的科学成就之一,但过度使用正给医学的未来带来挑战。抗生素耐药性(AR)被认为会导致肠道习惯改变和肠胃炎风险增加,但它也可能增加超重、肥胖、自身免疫性和过敏性疾病的风险,以及对疫苗和癌症的低反应性,这可能是由抗生素引起的肠道微生物群失调介导的。益生菌辅助治疗可以部分预防抗生素引起的肠道微生物群失调,但其抗生素敏感性特征可能限制了这种潜力。欧洲食品安全局(EFSA)的指南认为,使用其抗生素耐药性特征可能会转移的益生菌是一个重要危害。最近,一株(PRL2020)通过按照EFSA指南应用微量稀释方案,已显示出对阿莫西林和阿莫西林-克拉维酸(AC)具有耐药性。在验证不太可能发生水平基因转移后,这一特征表明它可与这些特定抗生素同时使用。我们的测试结果表明,菌株PRL2020确实具有对阿莫西林和AC的耐药特性,并且对氨苄西林也不敏感。对PRL2020注释基因组序列进行深入分析,使用耐药基因标识符(RGI)软件(版本5.2.1)查询综合抗生素耐药数据库(CARD)。通过核苷酸序列比对研究发现的AR决定因素之间的相似性,不仅可以验证侧翼区域中不存在解释这些特征的基因,还可以验证可能负责利福平耐药性和红霉素耐药性的遗传序列(和)的存在。这两种特征在表型上均未表达,对于这些抗生素,该菌株在EFSA规定的范围内。对这些基因侧翼区域的分析仅在基因的情况下揭示了上下游可能存在的移动元件,但插入序列(IS)的特征被描述为不会导致水平转移。我们对菌株PRL2020的研究结果表明,其AR特征在旨在降低微生物群失调风险时与抗生素是相容的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc8/10383950/8fab62eb946d/microorganisms-11-01649-g001.jpg

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