美國(guó)科學(xué)家的一項(xiàng)最新研究,，揭開了“超級(jí)細(xì)菌”橫行霸道的作用機(jī)制,。他們發(fā)現(xiàn)，這類抗藥性最強(qiáng),、最為兇殘的金黃色葡萄球菌(S. aureus)能通過釋放一種致命的“分子炸彈”,，摧毀人體免疫系統(tǒng)。相關(guān)論文11月9日在線發(fā)表于《自然—醫(yī)學(xué)》上,。
抗藥性金黃色葡萄球菌(MRSA)可以抵抗最強(qiáng)力的抗生素和藥物,，并能夠引起各種感染,，因此也被稱為“超級(jí)細(xì)菌”(Superbug)。美國(guó)每年因“超級(jí)細(xì)菌”導(dǎo)致的死亡人數(shù)可達(dá)到18000例,，超過了2005年美國(guó)死于艾滋病的16000人,。同時(shí)，感染“超級(jí)細(xì)菌”的人數(shù)也在越來(lái)越多,，1974年感染葡萄球菌的人中只有2%是MRSA,，而到了2003年，這一數(shù)字達(dá)到了64%,。感染“超級(jí)細(xì)菌”后的癥狀包括丘疹,、肺炎等。
在最新的研究中,，美國(guó)國(guó)立過敏和傳染病研究所(NIAID)的微生物學(xué)家Michael Otto和同事發(fā)現(xiàn),，MRSA可以產(chǎn)生一類酚可溶性蛋白(PSMs)，這賦予了它們強(qiáng)大的威力,。值得注意的是,，這很可能是MRSA眾多“詭計(jì)”的其中之一。
Otto的小組在實(shí)驗(yàn)室中培育出了一些PSM分子,，并且將其應(yīng)用于人類嗜中性粒細(xì)胞(neutrophil,，一種人類免疫細(xì)胞，人體抵御葡萄球菌的第一道防線),。結(jié)果發(fā)現(xiàn),，數(shù)分鐘后，這些免疫細(xì)胞開始變平,，一個(gè)小時(shí)后,，許多免疫細(xì)胞都遭到破壞。Otto表示,，“我們認(rèn)為,，這就是金黃色葡萄球菌擺脫主要‘敵人’的方式。”
研究人員還對(duì)醫(yī)院和社區(qū)獲得性MRSA菌系進(jìn)行了對(duì)比研究,。盡管后者比前者抵抗的藥物種類略少,，但卻更加兇殘，往往在數(shù)天內(nèi)就能致人于死地,。研究結(jié)果表明,，幾種社區(qū)獲得性MRSA菌系能夠制造更多的PSM，而大多數(shù)的醫(yī)院菌系并不制造該蛋白,。研究人員認(rèn)為,，這可能就是社區(qū)獲得性MRSA威力更加強(qiáng)大的原因。
進(jìn)一步的研究證實(shí)了這一觀點(diǎn)。當(dāng)研究人員移除與編碼PSM相關(guān)的基因后,，社區(qū)獲得性MRSA對(duì)小鼠的威脅程度降低,，同時(shí)在小鼠皮膚上留下的膿腫塊也較少。
美國(guó)加州大學(xué)舊金山分校的微生物學(xué)家和醫(yī)師Henry Chambers表示,，盡管PSM對(duì)理解社區(qū)獲得性MRSA十分重要，但它只是“冰山一角”,。“認(rèn)為葡萄球菌具有‘一刀切’的機(jī)制是一種天真的想法,，因?yàn)樗鼈兊姆N類太多了，”Chambers說(shuō),。
Otto的小組正致力于創(chuàng)造PSM抗血清,，并在小鼠身上進(jìn)行試驗(yàn)。(科學(xué)網(wǎng)任霄鵬/編譯)
原始出處:
Nature Medicine
Published online: 11 November 2007 | doi:10.1038/nm1656
Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA
Rong Wang1, Kevin R Braughton1, Dorothee Kretschmer2, Thanh-Huy L Bach1, Shu Y Queck1, Min Li1, Adam D Kennedy1, David W Dorward3, Seymour J Klebanoff4, Andreas Peschel2, Frank R DeLeo1 & Michael Otto1
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings1, 2. In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room3. It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
Cellular and Molecular Microbiology Unit, Medical Microbiology and Hygiene Department, University of Tübingen, Elfriede-Auhorn-Str. 6, 72076 Tübingen, Germany.
Microscopy Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, Washington 98195, USA.
Correspondence to: Michael Otto1 e-mail: [email protected]
