Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, United Kingdom.
Antimicrob Agents Chemother. 2010 Jan;54(1):380-7. doi: 10.1128/AAC.00155-09. Epub 2009 Oct 26.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are complicated by the ability of the organism to grow in surface-adhered biofilms on a multitude of abiotic and biological surfaces. These multicellular communities are notoriously difficult to eradicate with antimicrobial therapy. Cells within the biofilm may be exposed to a sublethal concentration of the antimicrobial due to the metabolic and phenotypic diversity of the biofilm-associated cells or the protection offered by the biofilm structure. In the present study, the influence of a sublethal concentration of tigecycline on biofilms formed by an epidemic MRSA-16 isolate was investigated by transcriptome analysis. In the presence of the drug, 309 genes were upregulated and 213 genes were downregulated by more than twofold in comparison to the levels of gene regulation detected for the controls not grown in the presence of the drug. Microarray data were validated by real-time reverse transcription-PCR and phenotypic assays. Tigecycline altered the expression of a number of genes encoding proteins considered to be crucial for the virulence of S. aureus. These included the reduced expression of icaC, which is involved in polysaccharide intercellular adhesin production and biofilm development; the upregulation of fnbA, clfB, and cna, which encode adhesins which attach to human proteins; and the downregulation of the cap genes, which mediate the synthesis of the capsule polysaccharide. The expression of tst, which encodes toxic shock syndrome toxin 1 (TSST-1), was also significantly reduced; and an assay performed to quantify TSST-1 showed that the level of toxin production by cells treated with tigecycline decreased by 10-fold (P < 0.001) compared to the level of production by untreated control cells. This study suggests that tigecycline may reduce the expression of important virulence factors in S. aureus and supports further investigation to determine whether it could be a useful adjunct to therapy for the treatment of biofilm-mediated infections.
耐甲氧西林金黄色葡萄球菌（MRSA）感染的复杂性在于该生物体能够在多种非生物和生物表面的表面附着生物膜中生长。这些多细胞群落对抗微生物治疗具有很强的抗性，极难消除。由于生物膜相关细胞的代谢和表型多样性或生物膜结构提供的保护，生物膜内的细胞可能会暴露于亚致死浓度的抗生素。在本研究中，通过转录组分析研究了亚致死浓度替加环素对流行的 MRSA-16 分离株形成的生物膜的影响。与未用药物生长的对照相比，药物存在时，有 309 个基因的表达上调，213 个基因的表达下调超过两倍。微阵列数据通过实时逆转录-PCR 和表型测定进行了验证。替加环素改变了许多编码被认为对金黄色葡萄球菌毒力至关重要的蛋白质的基因的表达。其中包括参与多糖细胞间黏附素产生和生物膜形成的 icaC 的表达减少；编码与人体蛋白结合的黏附素的 fnbA、clfB 和 cna 的上调；以及介导荚膜多糖合成的 cap 基因的下调。编码毒性休克综合征毒素 1 (TSST-1) 的 tst 的表达也显著降低；并且进行了一项定量测定 TSST-1 的实验，结果表明用替加环素处理的细胞产生的毒素水平比未处理的对照细胞减少了 10 倍（P < 0.001）。这项研究表明，替加环素可能会降低金黄色葡萄球菌中重要毒力因子的表达，并支持进一步研究，以确定它是否可作为治疗生物膜介导感染的辅助治疗方法。
