近日，來(lái)自加拿大阿爾伯塔大學(xué)的研究者在致病菌鮑氏不動(dòng)桿菌的分子保護(hù)層中發(fā)現(xiàn)了其“裂縫”,，這將為新型抗生素的開(kāi)發(fā)提供一些線索,，鮑氏不動(dòng)桿菌是20世紀(jì)70年代首次發(fā)現(xiàn)，在上個(gè)世紀(jì),，該菌已經(jīng)產(chǎn)生了極強(qiáng)的耐藥性,。
研究者Feldman識(shí)別出了一種新的機(jī)制，即鮑氏不動(dòng)桿菌可以以糖蛋白類來(lái)保護(hù)其菌體表面免受傷害,。這就引導(dǎo)這研究者去拉開(kāi)另一個(gè)發(fā)現(xiàn),，如果鮑氏不動(dòng)桿菌不能產(chǎn)生糖蛋白類，則細(xì)菌將變得低毒而且會(huì)產(chǎn)生較少的生物被膜（生物被膜可以保護(hù)細(xì)菌免于抗生素傷害）,。
鮑氏不動(dòng)桿菌是一種狡猾的接觸傳染性病菌，可以在醫(yī)院內(nèi)廣泛傳染,。這種細(xì)菌僅僅通過(guò)身體接觸就可以在人群中進(jìn)行傳染,，而且在堅(jiān)硬表面可以生存數(shù)日，并且可以以導(dǎo)尿管和呼吸器為寄居地,。不動(dòng)桿菌感染也可以通過(guò)咳嗽和打噴嚏來(lái)傳播,。
免疫力低下的病人通常對(duì)鮑氏不動(dòng)桿菌有較強(qiáng)的敏感性，而且細(xì)菌感染傷口后可以擴(kuò)散至肺部,、血液中以及腦部,。研究者表示需要更為深入的工作來(lái)理解細(xì)菌是如何產(chǎn)生多糖類物質(zhì)的,，研究者希望他們當(dāng)前的研究可以為研發(fā)抵御或阻止多糖類產(chǎn)生的藥物提供思路，并且研究者希望通過(guò)深入研究最終找到徹底殺滅鮑氏不動(dòng)桿菌的方法,。
這項(xiàng)研究已于6月7日刊登在了國(guó)際著名雜志PLoS Pathogens上,。（生物谷Bioon.com）
編譯自：Killer Hospital Bacteria: Cracking a Superbug's Armour
編譯者：天使托
doi:10.1371/journal.ppat.1002758
PMC:
PMID:
Identification of a General O-linked Protein Glycosylation System in Acinetobacter baumannii and Its Role in Virulence and Biofilm Formation
Jeremy A. Iwashkiw1, Andrea Seper2, Brent S. Weber1, Nichollas E. Scott1,3, Evgeny Vinogradov4, Chad Stratilo5, Bela Reiz6, Stuart J. Cordwell3, Randy Whittal6, Stefan Schild2, Mario F. Feldman1*
Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening “superbugs” for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics.
