最近,，英國桑格研究所（Wellcome Trust Sanger Institute）和布里斯托爾大學(xué)的研究者們共同完成了一種名為Steno的超級細(xì)菌的基因測序工作,，研究結(jié)果顯示，這是一種具有顯著抗藥性的生物體,。對這種細(xì)菌基因組的了解將有助于研究者們發(fā)現(xiàn)如何應(yīng)對這種具有獨(dú)特抗藥性的生物體,。這一研究論文發(fā)表在《基因組生物學(xué)》（Genome Biology）上,。
在英國每年有接近1000例的Steno敗血病病例,，死亡率大約30%。這種細(xì)菌在許多患有囊性纖維化病的成年人肺部也有發(fā)現(xiàn),，可以引起呼吸機(jī)相關(guān)性肺炎,，在年長的重病護(hù)理患者中尤其顯著。
布里斯托爾大學(xué)的Matthew Avison教授表示,，“Steno是一類最新發(fā)現(xiàn)的名單不斷增加的醫(yī)院超級細(xì)菌,，它們顯示出的抗藥性程度令人擔(dān)憂。新出現(xiàn)的菌株可以抵抗所有的抗生素,，而當(dāng)前尚沒有開發(fā)出真對抗這種全耐菌株的新藥,。”
全耐Steno感染的治療難度不亞于已知的MRSA和C.diff，但這種傳染更加罕見,，只在醫(yī)院環(huán)境中獲得,。MRSA是一種金黃色葡萄球菌，它對甲氧苯青霉素和其它抗生素有抗藥性,。C. diff通常情況下存在于大腸中,，被認(rèn)為是對健康人體有益的細(xì)菌?？股氐氖褂脮沟肅. diff成倍滋生,，產(chǎn)生大量的毒素而導(dǎo)致感染。
Steno通常在潮濕的環(huán)境下繁殖,，可以粘附在導(dǎo)管表面形成生物薄層,，通過長期使用的導(dǎo)尿管或?qū)夤芸梢赃M(jìn)入人體。這些導(dǎo)管常用于重癥患者或者化療中的病人,。如果病人的免疫系統(tǒng)較為脆弱,，那么Steno就可以大量在體內(nèi)繁殖從而引起敗血病。這些病人會被用抗生素來治療,，而這些抗生素恰巧是Steno所抵抗的,，這一情況已經(jīng)在新的研究中得到了重視,。
科學(xué)家需要解決的關(guān)鍵性問題包括：Steno是如何粘附在導(dǎo)尿管和導(dǎo)氣管表面的？如何形成生物薄層并無法被清洗干凈,？為什么它可以抵抗抗生素,？桑格研究所的第一作者Lisa Crossman博士解釋了她們的研究可以解決上述問題：“基因組序列可以幫助我們對抗Steno的這些特性。比如,，如果我們知道了它通過哪一個(gè)蛋白質(zhì)粘附在導(dǎo)管表面,，我們就可以去開發(fā)生化試劑來干擾這一過程；如果我們掌握了它的抗藥性機(jī)理,，那么就可以設(shè)計(jì)抑制劑來使之封閉,。”
盡管Steno傳染還比較少，但趨勢卻是不斷增加,。另外兩種引起相似類型傳染的MRSA和C.diff卻比較常見,。Avison說，“這兩類生物體的基因組序列已經(jīng)存在,，所以現(xiàn)在我們可以著眼于研究這三種超級細(xì)菌在遺傳上的共同特性,，這將有助于解釋為何它們對抗生素具有如此的抵抗性。”（科學(xué)網(wǎng) 劉巍 任霄鵬/編譯）
生物谷推薦原始出處：
Genome Biology,，2008, 9:R74 doi:10.1186/gb-2008-9-4-r74,，Lisa C Crossman , Matthew B Avison
The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants
Lisa C Crossman1 , Virginia C Gould2 , J Maxwell Dow3 , Georgios S Vernikos1 , Aki Okazaki2 , Mohammed Sebaihia1 , David Saunders1 , Claire Arrowsmith1 , Tim Carver1 , Nicholas Peters1 , Ellen Adlem1 , Arnaud Kerhornou1 , Angela Lord1 , Lee Murphy1 , Katharine Seeger1 , Robert Squares1 , Simon Rutter1 , Michael A Quail1 , Mari-Adele Rajandream1 , David Harris1 , Carol Churcher1 , Stephen D Bentley1 , Julian Parkhill1 , Nicholas R Thomson1 and Matthew B Avison2
1Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK
2Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
3Biomerit Research Centre, Department of Microbiology, Biosciences Institute, National University of Ireland, Cork, Ireland
Abstract
Background
Stenotrophomonas maltophilia is a nosocomial opportunistic pathogen of the Xanthomonadaceae. The organism has been isolated from both clinical and soil environments in addition to the sputum of cystic fibrosis patients and the immunocompromised. Whilst relatively distant phylogenetically, the closest sequenced relatives of S. maltophilia are the plant pathogenic xanthomonads.
Results
The genome of the bacteremia-associated isolate S. maltophilia K279a is 4,851,126 bp and of high G+C content. The sequence reveals an organism with a remarkable capacity for drug and heavy metal resistance. In addition to a number of genes conferring resistance to antimicrobial drugs of different classes via alternative mechanisms, nine resistance-nodulation-division (RND)-type putative antimicrobial efflux systems are present. Functional genomic analysis confirms a role in drug resistance for several of the novel RND efflux pumps. S. maltophilia possesses potentially mobile regions of DNA and encodes a number of pili and fimbriae likely to be involved in adhesion and biofilm formation that may also contribute to increased antimicrobial drug resistance.
Conclusion
The panoply of antimicrobial drug resistance genes and mobile genetic elements found suggests that the organism can act as a reservoir of antimicrobial drug resistance determinants in a clinical environment, which is an issue of considerable concern.
