ESAT-6 Secretion in Staphylococcus Aureus

由金黄色葡萄球菌引起的人类感染是一种严重的治疗方法， 由于出现了耐药菌株而受到挑战。主要关注的是 耐甲氧西林链球菌感染。金黄色葡萄球菌（MRSA），高毒力微生物 也是美国医院里最常见的传染病MRSA已获得 对所有已知抗生素的耐药机制，许多分离株具有广泛的耐药性 对抗大多数抗感染药物未来的研究必须着眼于了解 MRSA发病机制的分子生物学和特异性疫苗的开发， 预防MRSA感染性疾病。这个提议揭示了一种特殊的分泌物 系统的S.金黄色葡萄球菌，其参与人类和动物感染的发病机制。 色葡萄金黄色葡萄球菌ESS（ESAT-6分泌系统）基因座由一簇8个基因组成， 其中三个（esxA，esxB和esaC）编码由一种 需要机械基因essABC的机制。在感染过程中， 人类宿主对EsxA、EsxB和EsaC产生体液免疫应答，表明 所有临床S.金黄色葡萄球菌分离株在体内参与Ess分泌。我们证明了S.金黄色 导致实验动物持续感染，类似于葡萄球菌病， 人类葡萄球菌感染的发病机制需要Ess途径， 因为esxB突变体不能形成寄生物或在宿主组织中持续存在，而 影响EsaC分泌的突变体最初复制，但随后不能持续。动物 首先感染野生型S.金黄色葡萄球菌仍然对随后的葡萄球菌 感染，而感染esxB突变体的动物对随后的感染产生免疫力。 S.金黄色葡萄球菌感染在这里，我们将探讨S的Ess途径。金黄色的解开 脓肿形成和持续感染的分子基础。此外，委员会认为， 询问葡萄球菌esxB突变体的遗传要求， 抗S.金黄色葡萄球菌病

Human infections caused by Staphylococcus aureus present a serious therapeutic challenge due to the emergence of antibiotic-resistant strains. Of major concern are infections with methicillin-resistant S. aureus (MRSA), highly virulent microorganisms and the most common infectious disease in American hospitals. MRSA have acquired resistance mechanisms to all known antibiotics and many isolates are broadly resistant against most antiinfective agents. Future research must aim at understanding the molecular biology of MRSA pathogenesis and the development of specific vaccines that prevent MRSA infectious diseases. This proposal reveals a specialized secretion system of S. aureus that is involved in the pathogenesis of human and animal infections. The S. aureus ess (ESAT-6 secretion system) locus consists of a cluster of eight genes, three of which (esxA, esxB and esaC) encode products that are secreted by a mechanism requiring the machinery genes essABC. During infection, both murine and human hosts generate humoral immune responses to EsxA, EsxB and EsaC, suggesting that all clinical S. aureus isolates engage Ess secretion in vivo. We show that S. aureus causes persistent infections in experimental animals, similar to staphylococcal disease in humans. The Ess pathway is required for the pathogenesis of staphylococcal infections, as esxB mutants are unable to form abscesses or persist in host tissues, whereas mutants that impact EsaC secretion initially replicate but then fail to persist. Animals first infected with wild-type S. aureus remain susceptible to subsequent staphylococcal infection, whereas animals infected with esxB mutants develop immunity to subsequent S. aureus infections. Here we will explore the Ess pathway of S. aureus to unravel the molecular basis of abscess formation and persistent infections. Moreover, staphylococcal esxB mutants are interrogated for the genetic requirements of generating protective immunity against S. aureus disease.