生物谷：在過去的三十年中,，鏈球菌感染（strep infection）引發(fā)了越來越多的疾病,，而這一切的“始作俑者”就是一類稱作M1T1的鏈球菌菌株。加州大學圣地亞哥分校醫(yī)學院和澳大利亞的臥龍崗大學(University of Wollongong)的研究者,，發(fā)現(xiàn)了這個菌株的來歷：30年前,，一個病毒感染了鏈球菌，從而誕生出了一個致命性菌株,，并一步一步地演變成為今日可引起多種人類傳染病的菌株,。
鏈球菌可引起許多疾病，如簡單的喉嚨,、皮膚感染,，到致命的感染癥狀，包括壞死性筋膜炎（又名“食肉病”）和毒性休克綜合癥,。據(jù)估計,，鏈球菌大約每年引起了7億次感染事件，其中超過65萬次為危險性的感染事件,。“正如計算機病毒可能侵入并操控你的電腦一樣,，這個病毒重組了M1T1鏈球菌，讓它呈現(xiàn)出了更多的病毒特征,，” 文章通訊作者Victor Nizet介紹,，“這個侵入事件的危害直到30年后，人類仍然能夠感受到,。”
研究者揭示出了入侵性M1T1鏈球菌毒性如此高的內(nèi)在機制,。他們發(fā)現(xiàn)，在簡單的皮膚感染早期,，一小部分的鏈球菌會在人類的血液中,，“劫持”一類稱作血纖維蛋白溶酶原（plasminogen）的蛋白。鏈球菌的表面與此蛋白接觸,，隨后將之激活成一種蛋白酶,，一種可消化蛋白、破壞細胞和組織的酶,，這就為細菌在體內(nèi)的暴發(fā)和傳播創(chuàng)造好條件,。
此項研究的成果刊登在了7月15日的Nature Medicine在線期刊上。（生命經(jīng)緯）
原始出處:
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: [email protected]
