Krahn Thomas, Wibberg Daniel, Maus Irena, Winkler Anika, Bontron Séverine, Sczyrba Alexander, Nordmann Patrice, Pühler Alfred, Poirel Laurent, Schlüter Andreas
Institute for Genome Research and Systems Biology, Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany.
Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
Antimicrob Agents Chemother. 2016 Apr 22;60(5):3032-40. doi: 10.1128/AAC.00124-16. Print 2016 May.
The species Acinetobacter baumannii is one of the most important multidrug-resistant human pathogens. To determine its virulence and antibiotic resistance determinants, the genome of the nosocomial blaNDM-1-positive A. baumannii strain R2090 originating from Egypt was completely sequenced. Genome analysis revealed that strain R2090 is highly related to the community-acquired Australian A. baumannii strain D1279779. The two strains belong to sequence type 267 (ST267). Isolate R2090 harbored the chromosomally integrated transposon Tn125 carrying the carbapenemase gene blaNDM-1 that is not present in the D1279779 genome. To test the transferability of the metallo-β-lactamase (MBL) gene region, the clinical isolate R2090 was mated with the susceptible A. baumannii recipient CIP 70.10, and the carbapenem-resistant derivative R2091 was obtained. Genome sequencing of the R2091 derivative revealed that it had received an approximately 66-kb region comprising the transposon Tn125 embedding the blaNDM-1 gene. This region had integrated into the chromosome of the recipient strain CIP 70.10. From the four known mechanisms for horizontal gene transfer (conjugation, outer membrane vesicle-mediated transfer, transformation, and transduction), conjugation could be ruled out, since strain R2090 lacks any plasmid, and a type IV secretion system is not encoded in its chromosome. However, strain R2090 possesses three putative prophages, two of which were predicted to be complete and therefore functional. Accordingly, it was supposed that the transfer of the resistance gene region from the clinical isolate R2090 to the recipient occurred by general transduction facilitated by one of the prophages present in the R2090 genome. Hence, phage-mediated transduction has to be taken into account for the dissemination of antibiotic resistance genes within the species A. baumannii.
鲍曼不动杆菌是最重要的多重耐药人类病原体之一。为了确定其毒力和抗生素耐药决定因素,对源自埃及的医院内blaNDM-1阳性鲍曼不动杆菌菌株R2090的基因组进行了全测序。基因组分析表明,菌株R2090与社区获得性澳大利亚鲍曼不动杆菌菌株D1279779高度相关。这两个菌株属于序列类型267(ST267)。分离株R2090含有携带碳青霉烯酶基因blaNDM-1的染色体整合转座子Tn125,该基因不存在于D1279779基因组中。为了测试金属β-内酰胺酶(MBL)基因区域的可转移性,将临床分离株R2090与敏感的鲍曼不动杆菌受体CIP 70.10进行接合,获得了耐碳青霉烯衍生物R2091。R2091衍生物的基因组测序表明,它获得了一个约66 kb的区域,该区域包含嵌入blaNDM-1基因的转座子Tn125。该区域已整合到受体菌株CIP 70.10的染色体中。从水平基因转移的四种已知机制(接合、外膜囊泡介导的转移、转化和转导)来看,接合可以排除,因为菌株R2090缺乏任何质粒,并且其染色体中未编码IV型分泌系统。然而,菌株R2090拥有三个推定的原噬菌体,其中两个预计是完整的,因此具有功能。因此,推测耐药基因区域从临床分离株R2090转移到受体是由R2090基因组中存在的一个原噬菌体促进的一般转导所致。因此,在鲍曼不动杆菌物种内抗生素耐药基因的传播中必须考虑噬菌体介导的转导。