title: Evolution of carbapenem-resistant Acinetobacter baumannii revealed through whole-genome sequencing and comparative genomic analysis.
abstract: Acinetobacter baumannii is a globally important nosocomial pathogen characterized by an evolving multidrug resistance. A total of 35 representative clinical A. baumannii strains isolated from 13 hospitals in nine cities in China from 1999 to 2011, including 32 carbapenem-resistant and 3 carbapenem-susceptible A. baumannii strains, were selected for whole-genome sequencing and comparative genomic analysis. Phylogenetic analysis revealed that the earliest strain, strain 1999BJAB11, and two strains isolated in Zhejiang Province in 2004 were the founder strains of carbapenem-resistant A. baumannii. Ten types of AbaR resistance islands were identified, and a previously unreported AbaR island, which comprised a two-component response regulator, resistance-related proteins, and RND efflux system proteins, was identified in two strains isolated in Zhejiang in 2004. Multiple transposons or insertion sequences (ISs) existed in each strain, and these gradually tended to diversify with evolution. Some of these IS elements or transposons were the first to be reported, and most of them were mainly found in strains from two provinces. Genome feature analysis illustrated diversified resistance genes, surface polysaccharides, and a restriction-modification system, even in strains that were phylogenetically and epidemiologically very closely related. IS-mediated deletions were identified in the type VI secretion system region, the csuE region, and core lipooligosaccharide (LOS) loci. Recombination occurred in the heme utilization region, and intrinsic resistance genes (blaADC and blaOXA-51-like variants) and three novel blaOXA-51-like variants (blaOXA-424, blaOXA-425, and blaOXA-426) were identified. Our results could improve the understanding of the evolutionary processes that contribute to the emergence of carbapenem-resistant A. baumannii strains and help elucidate the molecular evolutionary mechanism in A. baumannii.
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Henan
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China whuibj@163.com huyf@im.ac.cn.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China whuibj@163.com huyf@im.ac.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D004251:DNA Transposable Elements / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D016680:Genome, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004251:DNA Transposable Elements