华东师大生命科学学院吴自荣教授指导的博士研究生赖玉平与美国国家卫生研究所米歇尔·奥托博士合作，研究发现了控制革兰氏阳性菌感应抗菌肽的三原素感应系统。该研究成果以赖玉平为并列第一作者发表于美国科学院院刊PNAS上。日前，权威的《自然微生物学》杂志将该成果评为微生物领域2007年上半年的突出研究成果。
三原素感应系统就像一把钥匙，控制着细菌细胞膜表面抗抗菌肽基因（Dlt和mprF）的开关。这项研究成果解答了为什么一些细菌能生存于人的表皮从而与人共生的机理，同时为开发新型抗菌药物提供了新的靶点。
据介绍，表皮葡萄球菌是人皮肤上的主要共生菌，通常情况下不会引起人类疾病。但是一旦附着在一些人造器官上，当这些器官移植入人体后，就会使病人产生许多并发症。而这些表皮葡萄球菌很难被抗生素杀死，但其机理尚不清楚。
赖玉平利用基因芯片技术发现表皮葡萄球菌在被人抗菌肽防御素3刺激后，许多基因的表达发生改变，其中最重要的一个是ABC转运子表达的上调。接着，她们又利用基因敲除技术，证明了三原素的调节子是感应抗菌肽、从而调节表皮葡萄球菌抗抗菌肽的独特调节子，而这一调节子与目前所发现的革兰氏阴性菌抗抗菌肽的二元素调节子完全不同，是革兰氏阳性菌所特有的。
专家表示，由于长期抗生素的滥用，导致许多细菌，特别是致病菌产生了耐药性，这已经成为目前医学界一个世界性难题。研究致病菌的耐药机制以及研发出新型抗菌药物迫在眉睫。美国国家卫生研究所过敏与感染所所长Anthony S.Fauci,M.D高度评价了赖玉平等人的此项研究成果，“这为解决抗生素耐药性问题、设计新型抗菌药物开辟了新的道路。”
原始出处:
Published online before print May 21, 2007, 10.1073/pnas.0702159104
PNAS | May 29, 2007 | vol. 104 | no. 22 | 9469-9474
Gram-positive three-component antimicrobial peptide-sensing system
Min Li*, Yuping Lai*,,, Amer E. Villaruz*, David J. Cha*, Daniel E. Sturdevant, and Michael Otto*,¶
*Laboratory of Human Bacterial Pathogenesis and Research and Technology Branch, Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and School of Life Science, East China Normal University, Shanghai 200062, China
Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved April 19, 2007 (received for review March 8, 2007)
To survive during colonization or infection of the human body, microorganisms must circumvent mechanisms of innate host defense. Antimicrobial peptides represent a key component of innate host defense, especially in phagocytes and on epithelial surfaces. However, it is not known how the clinically important group of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed defensive response. By determining the genome-wide gene regulatory response to human -defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we discovered an antimicrobial peptide sensor system that controls major specific resistance mechanisms of Gram-positive bacteria and is unrelated to the Gram-negative PhoP/PhoQ system. It contains a classical two-component signal transducer and an unusual third protein, all of which are indispensable for signal transduction and antimicrobial peptide resistance. Furthermore, our data indicate that a very short, extracellular loop with a high density of negative charges in the sensor protein is responsible for antimicrobial peptide binding and the observed specificity for cationic antimicrobial peptides. Our study shows that Gram-positive bacteria have developed an efficient and unique way of controlling resistance mechanisms to antimicrobial peptides, which may provide a promising target for antimicrobial drug development.
innate host defense | Staphylococcus epidermidis
