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临床耐药链球菌中对大环内酯类、拉科酰胺和链阳菌素耐药的表型和基因型特征及其与杀菌剂敏感性降低的相关性。

Phenotypic and genotypic characteristics of macrolide, lacosamide, and streptogramin resistance in clinically resistant Streptococci and their correlation with reduced biocide susceptibility.

作者信息

Abdel-Karim Safaa A, Serry Fathy M, Elmasry Eman M, Hegazy Wael A H

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.

出版信息

BMC Med. 2025 May 13;23(1):281. doi: 10.1186/s12916-025-04097-9.

DOI:10.1186/s12916-025-04097-9
PMID:40361106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12076902/
Abstract

BACKGROUND

Gram-positive Streptococci is a huge group of different species that are classified based on its hemolytic effect besides the C-substance in the cell wall. This study focuses on the investigation of the prevalence and genetic basis of resistance to macrolides, lincosamides, and streptogramins (MLS) in α- and β-hemolytic Streptococci.

METHODS

Streptococcal isolates were identified and their resistance was assessed to MLS antibiotics through phenotypic analysis and genotypic screening of resistance genes. Isolates were also tested for susceptibility to antiseptics/disinfectants. The correlation between high MLS antibiotic resistance and reduced susceptibility to biocides was assessed. Efflux pump activity in the most resistant isolates (to both MLS antibiotics and biocides) was investigated.

RESULTS

The susceptibility testing indicates an increasing resistance to MLS, particularly macrolides (erythromycin, azithromycin, and clarithromycin) and lincomycin. By screening the resistance, the most predominant phenotype is the constitutive (cMLS) one, while the erm genes, particularly ermB, are the most detected genotype. Furthermore, the esterase-encoding gene ereA is widely distributed in the streptococcal isolates. By evaluating the minimum inhibitory concentrations (MICs) to different biocides, there was a strong relation between the increased MIC values to both MLS antibiotics and tested biocides. This can be attributed mainly to the transferable ermB gene and the enhanced bacterial efflux.

CONCLUSIONS

A significant correlation exists between reduced biocide susceptibility and resistance to MLS antibiotics. Elevated efflux pump activity in MLS-resistant isolates suggests efflux mechanisms may contribute to dual resistance to antibiotics and biocides. However, cross-resistance is primarily driven by the horizontally transferable ermB gene, which confers resistance by targeting the 50S ribosomal subunit.

摘要

背景

革兰氏阳性链球菌是一大类不同的菌种,除了细胞壁中的C物质外,还根据其溶血作用进行分类。本研究重点调查α和β溶血链球菌对大环内酯类、林可酰胺类和链阳菌素(MLS)耐药性的流行情况及其遗传基础。

方法

对链球菌分离株进行鉴定,并通过表型分析和耐药基因的基因型筛选评估其对MLS抗生素的耐药性。还对分离株进行了防腐剂/消毒剂敏感性测试。评估了对MLS抗生素的高耐药性与对杀菌剂敏感性降低之间的相关性。研究了最耐药分离株(对MLS抗生素和杀菌剂均耐药)中的外排泵活性。

结果

药敏试验表明对MLS的耐药性在增加,尤其是对大环内酯类(红霉素、阿奇霉素和克拉霉素)和林可霉素。通过筛选耐药性,最主要的表型是组成型(cMLS),而erm基因,尤其是ermB,是最常检测到的基因型。此外,酯酶编码基因ereA在链球菌分离株中广泛分布。通过评估对不同杀菌剂的最低抑菌浓度(MIC),对MLS抗生素和测试杀菌剂的MIC值增加之间存在很强的相关性。这主要可归因于可转移的ermB基因和增强的细菌外排。

结论

对杀菌剂敏感性降低与对MLS抗生素耐药之间存在显著相关性。MLS耐药分离株中外排泵活性升高表明外排机制可能导致对抗生素和杀菌剂的双重耐药。然而,交叉耐药主要由水平可转移的ermB基因驱动,该基因通过靶向50S核糖体亚基赋予耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/7562109211b5/12916_2025_4097_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/7562109211b5/12916_2025_4097_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/27ee7499c7f6/12916_2025_4097_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/c3d1ea652fd7/12916_2025_4097_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/48005edcf497/12916_2025_4097_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/3fb7e3e43837/12916_2025_4097_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/3e151f7e52ef/12916_2025_4097_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/12076902/7562109211b5/12916_2025_4097_Fig8_HTML.jpg

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