Multiple pathways towards reduced membrane potential and concomitant reduction in aminoglycoside susceptibility in Staphylococcus aureus
Multiple pathways towards reduced membrane potential and concomitant reduction in aminoglycoside susceptibility in Staphylococcus aureus
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DOI：
10.1016/j.ijantimicag.2017.08.024
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发表时间：
2018-01-01
影响因子：
10.8
通讯作者：
Ingmer, Hanne
中科院分区：
文献类型：
--
作者：
Vestergaard, Martin;Nohr-Meldgaard, Katrine;Ingmer, Hanne
金黄色葡萄球菌是世界范围内危及生命和难以治疗的感染的原因，抗菌素耐药性日益受到关注。虽然获得性耐药性已被广泛研究，但对染色体决定簇的作用知之甚少，这些决定簇在失活后可能降低S。金黄色葡萄球菌对抗生素的敏感性本研究的目的是鉴定灭活后降低链球菌对氨基糖苷类药物敏感性的遗传决定因素。金黄色。内布拉斯加转座子突变库的1920个单基因失活的S。筛选金黄色葡萄球菌菌株JE2对庆大霉素的敏感性降低。Etest证实了9个突变体对这种抗生素的敏感性降低了2至16倍。所有被鉴定的基因都与电子传递链和能量代谢相关。四种突变株（menD、hemB、aroC和SAUSA300_0355）使庆大霉素敏感性降低最大，三种表现出小菌落变体表型，而其余突变株（qoxA、qoxB、qoxC、ndh和hemX）表现出与野生型相似的菌落形态。除hemX外，所有突变体均显示膜电位降低，表明庆大霉素摄取减少是导致敏感性降低的主要机制。本研究结果表明，S。金黄色葡萄球菌具有多个基因，这些基因在通过诱变失活时降低膜电位，从而降低庆大霉素的致死活性。(c)2017 Elsevier B.V.和国际化疗学会。All rights reserved.
Staphylococcus aureus is responsible for life-threatening and difficult-to-treat infections worldwide and antimicrobial resistance is an increasing concern. Whilst acquired resistance has been widely studied, little is known of the contributions from chromosomal determinants that upon inactivation may reduce the susceptibility of S. aureus to antibiotics. The aim of this study was to identify genetic determinants that upon inactivation reduce aminoglycoside susceptibility in S. aureus. The Nebraska Transposon Mutant Library of 1920 single-gene inactivations in S. aureus strain JE2 was screened for reduced susceptibility to gentamicin. Nine mutants were confirmed by Etest to display between 2- and 16-fold reduced susceptibility to this antibiotic. All of the identified genes were associated with the electron transport chain and energy metabolism. Four mutant strains (menD, hemB, aroC and SAUSA300_0355) conferred the largest decrease in gentamicin susceptibility and three exhibited a small colony variant phenotype, whereas the remaining mutants (qoxA, qoxB, qoxC, ndh and hemX) displayed colony morphology similar to the wild-type. All of the mutants, except hemX, displayed reduced membrane potential suggesting that reduced uptake of gentamicin is the predominant mechanism leading to reduced susceptibility. The results of this study demonstrate that S. aureus possesses multiple genes that upon inactivation by mutagenesis reduce the membrane potential and thereby reduce the lethal activity of gentamicin. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.