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Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK
Evolution, Medicine, and Public Health ( IF 5.143 ) Pub Date : 2020-09-07 , DOI: 10.1093/emph/eoaa031
Nicholas F Brazeau 1, 2 , Kara J Levinson 3, 4 , Asher Schranz 5 , Kara A Moser 1 , Ian Hollis 6 , Prashanth Iyer 6 , Christopher Chien 7 , Amanda Bowen 7 , David van Duin 5 , Anne Lachiewicz 5 , Tessa Andermann 5 , Melissa Jones 4 , Melissa Miller 3, 4 , Jonathan J Juliano 1, 5, 8 , Luther A Bartelt 5
Affiliation  

Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections.

中文翻译:

临床表皮葡萄球菌感染中达托霉素敏感性下降WalK变异同时发生

达托霉素(DAP)是治疗耐多药葡萄球菌感染的关键。表皮葡萄球菌菌株对DAP的敏感性正在降低,尽管对非敏感性(NS)的机制仍知之甚少。我们报告一例持续性表皮葡萄球菌菌血症,其中在长期治疗期间DAP敏感性下降。全基因组测序在单一影响的基因WalK中鉴定了两个突变Q371del和P415L,与DAP-NS的出现相吻合。突变的蛋白质模型预测了WalK蛋白质构型的破坏。在暴露于DAP的过程中,单一基因中突变的出现引起了人们的关注,在一个越来越具有治疗抗性的感染时代。
更新日期:2020-09-07
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