氟西地酸对金黄色葡萄球菌作用模式(MoA)和耐药模式(MoR)的代谢分析。

IF 2.2 4区 生物学 Q3 MICROBIOLOGY
Dan Luo, Juanjuan Ma, Weile Xie, Zhe Wang
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引用次数: 0

摘要

了解细菌对抗生素的反应对于确定耐药机制和开发新的治疗方法至关重要。本研究评估了100例皮肤和软组织感染(SSTIs)患者的金黄色葡萄球菌(S. aureus)对夫西地酸(FD)的耐药性,揭示了对FD的敏感性,尽管对其他抗生素有耐药性。通过适应性实验室进化,我们培育出了一株高度耐fd的菌株E10,并通过全基因组测序鉴定出3个基因突变(fusA、BPENGOFF-00211和rplF)。fusA突变是产生耐药性的主要因素。此外,进化的fusA突变株(H457Y)表现出凝血功能受损和生长速度降低。我们还分析了祖先ATCC 25923和进化的E10菌株的代谢组学特征,发现fusA基因可以独立诱导代谢重编程。这些变化主要影响中枢碳代谢、核苷酸代谢和氨基酸合成的途径。这项研究强调了金黄色葡萄球菌FD耐药的复杂性,并提供了与抗生素耐药相关的代谢途径的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolic analysis of the mode of action and mode of resistance of fusidic acid against Staphylococcus aureus.

Understanding bacterial responses to antibiotics is essential for identifying resistance mechanisms and developing novel therapies. This study evaluated the resistance of Staphylococcus aureus (S. aureus) to fusidic acid (FD) in 100 patients with skin and soft tissue infections (SSTIs), revealing susceptibility to FD despite resistance to other antibiotics. Through adaptive laboratory evolution, we developed a highly FD-resistant strain, E10, and identified three gene mutations (fusA, BPENGOFF-00211, and rplF) using whole-genome sequencing. The fusA mutation was the primary contributor to resistance. Furthermore, the evolved fusA mutant strain (H457Y) displayed impaired coagulation function and reduced growth rates. We also analyzed the metabolomic profiles of ancestral ATCC 25923 and evolved E10 strains, both treated and untreated with FD, revealing that the fusA gene can independently induce metabolic reprogramming. These changes primarily impacted pathways involved in central carbon metabolism, nucleotide metabolism, and amino acid synthesis. This study highlights the complexity of FD resistance in S. aureus and offers insights into the metabolic pathways associated with antibiotic resistance.

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来源期刊
Fems Microbiology Letters
Fems Microbiology Letters 生物-微生物学
CiteScore
4.30
自引率
0.00%
发文量
112
审稿时长
1.9 months
期刊介绍: FEMS Microbiology Letters gives priority to concise papers that merit rapid publication by virtue of their originality, general interest and contribution to new developments in microbiology. All aspects of microbiology, including virology, are covered. 2019 Impact Factor: 1.987, Journal Citation Reports (Source Clarivate, 2020) Ranking: 98/135 (Microbiology) The journal is divided into eight Sections: Physiology and Biochemistry (including genetics, molecular biology and ‘omic’ studies) Food Microbiology (from food production and biotechnology to spoilage and food borne pathogens) Biotechnology and Synthetic Biology Pathogens and Pathogenicity (including medical, veterinary, plant and insect pathogens – particularly those relating to food security – with the exception of viruses) Environmental Microbiology (including ecophysiology, ecogenomics and meta-omic studies) Virology (viruses infecting any organism, including Bacteria and Archaea) Taxonomy and Systematics (for publication of novel taxa, taxonomic reclassifications and reviews of a taxonomic nature) Professional Development (including education, training, CPD, research assessment frameworks, research and publication metrics, best-practice, careers and history of microbiology) If you are unsure which Section is most appropriate for your manuscript, for example in the case of transdisciplinary studies, we recommend that you contact the Editor-In-Chief by email prior to submission. Our scope includes any type of microorganism - all members of the Bacteria and the Archaea and microbial members of the Eukarya (yeasts, filamentous fungi, microbial algae, protozoa, oomycetes, myxomycetes, etc.) as well as all viruses.
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