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首页> 外文期刊>Frontiers in Microbiology >Factors Determining Staphylococcus aureus Susceptibility to Photoantimicrobial Chemotherapy: RsbU Activity, Staphyloxanthin Level, and Membrane Fluidity
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Factors Determining Staphylococcus aureus Susceptibility to Photoantimicrobial Chemotherapy: RsbU Activity, Staphyloxanthin Level, and Membrane Fluidity

机译：确定金黄色葡萄球菌对光抗菌药物化疗敏感性的因素：RsbU活性，葡萄球菌黄素水平和膜流动性

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Photoantimicrobial chemotherapy (PACT) constitutes a particular type of stress condition, in which bacterial cells induce a pleiotropic and as yet unexplored effect. In light of this, the key master regulators are of putative significance to the overall phototoxic outcome. In Staphylococcus aureus , the alternative sigma factor σ~(B)controls the expression of genes involved in the response to environmental stress. We show that aberration of any sigB operon genes in S. aureus USA300 isogenic mutants causes a pronounced sensitization (>5 log_(10)reduction in CFU drop) to PACT with selected photosensitizers, namely protoporphyrin diarginate, zinc phthalocyanine and rose bengal. This effect is partly due to aberration-coupled staphyloxanthin synthesis inhibition. We identified frequent mutations in RsbU, a σ~(B)activator, in PACT-vulnerable clinical isolates of S. aureus , resulting in σ~(B)activity impairment. Locations of significant changes in protein structure (IS256 insertion, early STOP codon occurrence, substitutions A230T and A276D) were shown in a theoretical model of S. aureus RsbU. As a phenotypic hallmark of PACT-vulnerable S. aureus strains, we observed an increased fluidity of bacterial cell membrane, which is a result of staphyloxanthin content and other yet unidentified factors. Our research indicates σ~(B)as a promising target of adjunctive antimicrobial therapy and suggests that enhanced cell membrane fluidity may be an adjuvant strategy in PACT.
机译：光抗菌化学疗法（PACT）构成了一种特殊的应激状态，其中细菌细胞诱导多效且尚未探索的作用。有鉴于此，关键的主调节剂对总体光毒性结果具有假定的重要性。在金黄色葡萄球菌中，替代的西格玛因子σ〜（B）控制与环境胁迫有关的基因的表达。我们显示，在金黄色葡萄球菌USA300同基因突变体中，任何sigB操纵子基因的畸变都会对PACT产生明显的敏化作用（CFU下降> 5 log_（10）降低），即选择了原卟啉二精氨酸盐，酞菁锌和玫瑰红。此作用部分归因于像差耦合的金黄色素合成抑制。我们在易受PACT感染的金黄色葡萄球菌临床分离株中鉴定了σ〜（B）活化剂RsbU的频繁突变，导致σ〜（B）活性受损。在金黄色葡萄球菌RsbU的理论模型中显示了蛋白质结构显着变化的位置（IS256插入，早期STOP密码子出现，替代A230T和A276D）。作为易受PACT感染的金黄色葡萄球菌菌株的表型特征，我们观察到细菌细胞膜的流动性增加，这是葡萄黄素含量和其他未知因素的结果。我们的研究表明σ〜（B）是辅助抗菌治疗的有希望的靶标，并表明增强细胞膜流动性可能是PACT的辅助策略。

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