生物谷:在过去的三十年中,链球菌感染(strep infection)引发了越来越多的疾病,而这一切的“始作俑者”就是一类称作M1T1的链球菌菌株。加州大学圣地亚哥分校医学院和澳大利亚的卧龙岗大学(University of Wollongong)的研究者,发现了这个菌株的来历:30年前,一个病毒感染了链球菌,从而诞生出了一个致命性菌株,并一步一步地演变成为今日可引起多种人类传染病的菌株。
链球菌可引起许多疾病,如简单的喉咙、皮肤感染,到致命的感染症状,包括坏死性筋膜炎(又名“食肉病”)和毒性休克综合症。据估计,链球菌大约每年引起了7亿次感染事件,其中超过65万次为危险性的感染事件。“正如计算机病毒可能侵入并操控你的电脑一样,这个病毒重组了M1T1链球菌,让它呈现出了更多的病毒特征,” 文章通讯作者Victor Nizet介绍,“这个侵入事件的危害直到30年后,人类仍然能够感受到。”
研究者揭示出了入侵性M1T1链球菌毒性如此高的内在机制。他们发现,在简单的皮肤感染早期,一小部分的链球菌会在人类的血液中,“劫持”一类称作血纤维蛋白溶酶原(plasminogen)的蛋白。链球菌的表面与此蛋白接触,随后将之激活成一种蛋白酶,一种可消化蛋白、破坏细胞和组织的酶,这就为细菌在体内的暴发和传播创造好条件。
此项研究的成果刊登在了7月15日的Nature Medicine在线期刊上。(生命经纬)
原始出处:
Nature Medicine
Published online: 15 July 2007 | doi:10.1038/nm1612
DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection
Mark J Walker1, Andrew Hollands1, Martina L Sanderson-Smith1, Jason N Cole1, Joshua K Kirk1, Anna Henningham1, Jason D McArthur1, Katrin Dinkla2, Ramy K Aziz3,4, Rita G Kansal4,5, Amelia J Simpson6, John T Buchanan6, Gursharan S Chhatwal2, Malak Kotb4,5 & Victor Nizet6,7
Most invasive bacterial infections are caused by species that more commonly colonize the human host with minimal symptoms. Although phenotypic or genetic correlates underlying a bacterium's shift to enhanced virulence have been studied, the in vivo selection pressures governing such shifts are poorly understood. The globally disseminated M1T1 clone of group A Streptococcus (GAS) is linked with the rare but life-threatening syndromes of necrotizing fasciitis and toxic shock syndrome1. Mutations in the GAS control of virulence regulatory sensor kinase (covRS) operon are associated with severe invasive disease, abolishing expression of a broad-spectrum cysteine protease (SpeB)2, 3 and allowing the recruitment and activation of host plasminogen on the bacterial surface4. Here we describe how bacteriophage-encoded GAS DNase (Sda1), which facilitates the pathogen's escape from neutrophil extracellular traps5, 6, serves as a selective force for covRS mutation. The results provide a paradigm whereby natural selection exerted by the innate immune system generates hypervirulent bacterial variants with increased risk of systemic dissemination.
School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
Department of Microbial Pathogenesis and Vaccine Development, Helmholtz Centre for Infection Research, Braunschweig D-38124, Germany.
Department of Microbiology and Immunology, Cairo University, Cairo, Egypt.
The Veterans Affairs Medical Center, Memphis, Tennessee 38163, USA.
The MidSouth Center for Biodefense and Security, Memphis, Tennessee 38163, USA.
Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0687, USA.
Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0687, USA.
Correspondence to: Mark J Walker1 e-mail: mwalker@uow.edu.au