RUI: Effects of the Antimicrobial Agent Triclosan on the Emergence of Antibiotic Resistant Staphylococcus Aureus

三氯生是一种广谱抗菌剂，目前在许多消费品中都有发现。三氯生抑制细菌酶烯丙酰基载体蛋白（ACP）还原酶。这种酶催化微生物体内脂肪酸生物合成的最后一步。一些研究表明，对三氯生的敏感性降低与喹诺酮类抗生素耐药性有关。喹诺酮类药物抑制细菌DNA代谢酶、DNA回转酶和拓扑异构酶IV。对喹诺酮类抗生素的耐药性与编码DNA回转酶、拓扑异构酶IV的基因或编码多药物外排泵的基因有关。三氯生耐药性也映射到编码多药物外排泵的基因或编码控制这些泵表达的调节蛋白的基因。该项目的主要重点是确定三氯生耐药性是否有助于金黄色葡萄球菌的抗生素耐药性。金黄色葡萄球菌是一种人类病原体，治疗由这种生物引起的感染的治疗方法已经变得有限。本实验室的初步研究证实了12株金黄色葡萄球菌临床和实验室菌株对三氯生的敏感性。其中10株检测到三氯生耐药性。在10株对三氯生耐药的菌株中，4株对喹诺酮类抗生素也耐药。该项目将利用分子生物学和生物化学实验进一步表征这些耐三氯生菌株的性质。抗生素耐药性的出现是致病菌中日益严重的问题。该项目的结果将导致更深入地了解消费者使用抗菌产品对抗生素耐药细菌出现的影响。

Triclosan is a broad spectrum antimicrobial agent that is currently found in many consumer goods. Triclosan inhibits the bacterial enzyme enoyl acyl carrier protein (ACP) reductase. This enzyme catalyzes the last step in fatty acid biosynthesis in microorganisms. Several studies have indicated that decreased susceptibility to triclosan correlates with quinolone antibiotic resistance. The quinolones inhibit the bacterial DNA metabolic enzymes, DNA gyrase and topoisomerase IV. Resistance to the quinolone antibiotics maps to the genes encoding DNA gyrase, topoisomerase IV, or to genes encoding multi-drug efflux pumps. Triclosan resistance also maps to genes encoding multi-drug efflux pumps or to genes encoding regulatory proteins that control the expression of these pumps. The primary focus of this project is to determine whether triclosan resistance contributes to antibiotic resistance in Staphylococcus aureus. S. aureus is a human pathogen for which therapeutic options for the treatment of infections caused by this organism have become limited. Preliminary studies by this laboratory have demonstrated the triclosan susceptibility profiles of 12 S. aureus clinical and laboratory strains. Triclosan resistance was detected in 10 of these strains. Among the 10 triclosan resistant strains, 4 are also resistant to the quinolone antibiotics. This project will use molecular biological and biochemical experiments to further characterize the nature of these triclosan resistant strains. The emergence of antibiotic resistance is a growing problem among pathogenic bacteria. The results of this project will lead to a deeper understanding of the impact of antimicrobial product usage by consumers on the emergence of antibiotic resistant bacteria.