Department of Rheumatology and Inflammation Research, University of Gothenburg, Göteborg, Sweden.
PLoS One. 2010 Dec 2;5(12):e14209. doi: 10.1371/journal.pone.0014209.
Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s) transported by Ecs is (are) still unknown.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine.
CONCLUSIONS/SIGNIFICANCE: Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.
Ecs 是一种位于需氧和兼性厌氧革兰阳性Firmicutes 中的三磷酸腺苷结合盒（ABC）转运蛋白。枯草芽孢杆菌 Ecs 的失活导致细菌表型发生多种变化，包括内膜蛋白水解的抑制。Ecs 转运的分子（s）仍不清楚。
方法/主要发现：在本研究中，我们在两种金黄色葡萄球菌菌株 Newman 和 LS-1 中突变了 ecsAB 操纵子。这些 Ecs 缺陷突变体的表型和功能特征表明生长缺陷、自溶增加和溶葡萄球菌素敏感性增加、细胞壁蛋白组成改变，包括葡萄球菌激酶前体形式以及细菌表面纹理改变。DNA 微阵列分析表明，Ecs 缺乏改变了毒力因子调节蛋白 Rot 的表达，同时改变了膜转运蛋白，特别是 ABC 转运蛋白和磷酸盐特异性转运系统、蛋白 A、黏附素和荚膜多糖生物合成蛋白的表达。在金黄色葡萄球菌血源性感染的小鼠模型中研究了 ecs 突变体的毒力。与野生型菌株接种的小鼠相比，接种 ecs 突变株的小鼠感染明显较轻，死亡率较低，体重减轻较轻，关节炎较轻，肾脏中金黄色葡萄球菌的持续时间较短。ecs 突变体对核糖体抗生素和植物生物碱 Chelerythrine 和血根碱的敏感性更高。
结论/意义：我们的结果表明，Ecs 是金黄色葡萄球菌毒力和抗菌耐药性所必需的，可能是因为 Ecs 的转运功能对于细胞壁的正常结构和功能是必需的。因此，靶向 Ecs 可能是对抗金黄色葡萄球菌感染的一种新方法。
