最近,英国桑格研究所(Wellcome Trust Sanger Institute)和布里斯托尔大学的研究者们共同完成了一种名为Steno的超级细菌的基因测序工作,研究结果显示,这是一种具有显著抗药性的生物体。对这种细菌基因组的了解将有助于研究者们发现如何应对这种具有独特抗药性的生物体。这一研究论文发表在《基因组生物学》(Genome Biology)上。
在英国每年有接近1000例的Steno败血病病例,死亡率大约30%。这种细菌在许多患有囊性纤维化病的成年人肺部也有发现,可以引起呼吸机相关性肺炎,在年长的重病护理患者中尤其显著。
布里斯托尔大学的Matthew Avison教授表示,“Steno是一类最新发现的名单不断增加的医院超级细菌,它们显示出的抗药性程度令人担忧。新出现的菌株可以抵抗所有的抗生素,而当前尚没有开发出真对抗这种全耐菌株的新药。”
全耐Steno感染的治疗难度不亚于已知的MRSA和C.diff,但这种传染更加罕见,只在医院环境中获得。MRSA是一种金黄色葡萄球菌,它对甲氧苯青霉素和其它抗生素有抗药性。C. diff通常情况下存在于大肠中,被认为是对健康人体有益的细菌。抗生素的使用会使得C. diff成倍滋生,产生大量的毒素而导致感染。
Steno通常在潮湿的环境下繁殖,可以粘附在导管表面形成生物薄层,通过长期使用的导尿管或导气管可以进入人体。这些导管常用于重症患者或者化疗中的病人。如果病人的免疫系统较为脆弱,那么Steno就可以大量在体内繁殖从而引起败血病。这些病人会被用抗生素来治疗,而这些抗生素恰巧是Steno所抵抗的,这一情况已经在新的研究中得到了重视。
科学家需要解决的关键性问题包括:Steno是如何粘附在导尿管和导气管表面的?如何形成生物薄层并无法被清洗干净?为什么它可以抵抗抗生素?桑格研究所的第一作者Lisa Crossman博士解释了她们的研究可以解决上述问题:“基因组序列可以帮助我们对抗Steno的这些特性。比如,如果我们知道了它通过哪一个蛋白质粘附在导管表面,我们就可以去开发生化试剂来干扰这一过程;如果我们掌握了它的抗药性机理,那么就可以设计抑制剂来使之封闭。”
尽管Steno传染还比较少,但趋势却是不断增加。另外两种引起相似类型传染的MRSA和C.diff却比较常见。Avison说,“这两类生物体的基因组序列已经存在,所以现在我们可以着眼于研究这三种超级细菌在遗传上的共同特性,这将有助于解释为何它们对抗生素具有如此的抵抗性。”(科学网 刘巍 任霄鹏/编译)
生物谷推荐原始出处:
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.