Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility
Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility
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DOI：
10.1128/aac.50.4.1463-1469.2006
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Shirtliff, ME
中科院分区：
文献类型：
--
作者：
Jabra-Rizk, MA;Meiller, TF;Shirtliff, ME
金黄色葡萄球菌是导致血流感染的主要病原体之一，它能够在宿主组织和留置的医疗设备上形成生物膜，并持续存在和引发疾病。由于对抗生素的耐药性不断增加，金黄色葡萄球菌引起的感染越来越难以治疗。特别是在生物膜环境中，微生物对抗菌剂表现出更强的耐药性。最近，法尼醇被描述为一种具有可能的抗菌特性的群体感应分子。在这项研究中，研究了法尼醇对耐甲氧西林和甲氧西林敏感的金黄色葡萄球菌菌株的影响。通过活力测定、生物膜形成评估和溴化乙锭摄取试验，表明法尼醇能够抑制生物膜形成并损害细胞膜完整性。通过琼脂圆盘扩散法和肉汤微量稀释法评估了法尼醇使金黄色葡萄球菌对抗菌剂敏感的能力。对于两种葡萄球菌菌株，法尼醇仅在高浓度（150μM）时能够逆转耐药性。然而，它在提高菌株对所有有一定敏感性的抗生素的抗菌效力方面非常成功。因此，对法尼醇和庆大霉素进行了协同试验，用暴露于不同浓度的这两种试剂的静态生物膜进行试验。在处理后0、4和24小时对收获的生物膜细胞进行平板计数表明，庆大霉素为最低抑菌浓度的2.5倍和法尼醇为100μM（22μg/ml）的联合作用能够使细菌数量减少超过2个对数单位，证明了这两种抗菌剂之间的协同作用。观察到的耐药菌株对抗菌剂的敏感性以及与庆大霉素的协同作用表明法尼醇作为一种辅助治疗剂在预防生物膜相关感染和促进耐药性逆转方面具有潜在应用。
Staphylococcus aureus is among the leading pathogens causing bloodstream infections able to form biofilms on host tissue and indwelling medical devices and to persist and cause disease. Infections caused by S. aureus are becoming more difficult to treat because of increasing resistance to antibiotics. In a biofilm environment particularly, microbes exhibit enhanced resistance to antimicrobial agents. Recently, farnesol was described as a quorum-sensing molecule with possible antimicrobial properties. In this study, the effect of farnesol on methicillin-resistant and -susceptible strains of S. aureus was investigated. With viability assays, biofilm formation assessment, and ethidium bromide uptake testing, farnesol was shown to inhibit biofilm formation and compromise cell membrane integrity. The ability of farnesol to sensitize S. aureus to antimicrobials was assessed by agar disk diffusion and broth microdilution methods. For both strains of staphylococci, farnesol was only able to reverse resistance at a high concentration (150 mu M). However, it was very successful at enhancing the antimicrobial efficacy of all of the antibiotics to which the strains were somewhat susceptible. Therefore, synergy testing of farnesol and gentamicin was performed with static biofilms exposed to various concentrations of both agents. Plate counts of harvested biotilm cells at 0, 4, and 24 h posttreatment indicated that the combined effect of gentamicin at 2.5 times the MIC and farnesol at 100 mu M (22 mu g/ml) was able to reduce bacterial populations by more than 2 log units, demonstrating synergy between the two antimicrobial agents. This observed sensitization of resistant strains to antimicrobials and the observed synergistic effect with gentamicin indicate a potential application for farnesol as an adjuvant therapeutic agent for the prevention of biofilm-related infections and promotion of drug resistance reversal.