Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK.
Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK.
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DOI：
10.1093/emph/eoaa031
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Bartelt LA
中科院分区：
文献类型：
--
作者：
Brazeau NF;Levinson KJ;Schranz A;Moser KA;Hollis I;Iyer P;Chien C;Bowen A;van Duin D;Lachiewicz A;Andermann T;Jones M;Miller M;Juliano JJ;Bartelt LA
达托霉素(DAP)是治疗耐多药葡萄球菌感染的关键药物。表皮葡萄球菌菌株对DAP的敏感性正在降低，尽管不敏感(NS)的机制仍然知之甚少。我们报告一例持续性表皮葡萄球菌菌血症，在长期治疗过程中出现DAP敏感性丧失。全基因组测序在单个受影响的基因Walk中发现了两个突变Q371del和P415L，这与DAP-NS的出现是一致的。突变的蛋白质模型预测了Walk蛋白质构型的破坏。在一个日益耐药的感染时代，在接触DAP期间出现单基因突变引起了人们的担忧。摘要：达托霉素是治疗葡萄球菌感染的重要抗生素。我们在一例临床表皮葡萄球菌感染中发现了与耐药性一致的Walk基因变异。临床医生、医院流行病学家和微生物学实验室需要意识到延长达托霉素治疗期间耐药性演变的可能性。
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. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.
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DOI：
10.1016/j.tig.2014.07.003
发表时间：
2014-09
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Köser CU;Ellington MJ;Peacock SJ
通讯作者：
Peacock SJ
影响因子：
--
作者：
Sakimura T;Kajiyama S;Adachi S;Chiba K;Yonekura A;Tomita M;Koseki H;Miyamoto T;Tsurumoto T;Osaki M
通讯作者：
Osaki M
影响因子：
4.9
作者：
Jiang, Jhih-Hang;Dexter, Carina;Peleg, Anton Y.
通讯作者：
Peleg, Anton Y.
影响因子：
5.2
作者：
Bayer AS;Schneider T;Sahl HG
通讯作者：
Sahl HG
影响因子：
3.7
作者：
Thomsen MC;Ahrenfeldt J;Cisneros JL;Jurtz V;Larsen MV;Hasman H;Aarestrup FM;Lund O
通讯作者：
Lund O