title: Clinical and Genomic Analysis of Liver Abscess-CausingKlebsiella pneumoniaeIdentifies New Liver Abscess-Associated Virulence Genes.
abstract: Hypervirulent variants ofKlebsiella pneumoniae(hvKp) that cause invasive community-acquired pyogenic liver abscess (PLA) have emerged globally. Little is known about the virulence determinants associated with hvKp, except for the virulence genesrmpA/A2and siderophores (iroBCD/iucABCD) carried by the pK2044-like large virulence plasmid. Here, we collected most recent clinical isolates of hvKp from PLA samples in China, and performed clinical, molecular, and genomic sequencing analyses. We found that 90.9% (40/44) of the pathogens causing PLA wereK. pneumoniae. Among the 40 LA-Kp, K1 (62.5%), and K2 (17.5%) were the dominant serotypes, and ST23 (47.5%) was the major sequence type. S1-PFGE analyses demonstrated that although 77.5% (31/40) of the LA-Kp isolates harbored a single large virulence plasmid varied in size, 5 (12.5%) isolates had no plasmid and 4 (10%) had two or three plasmids. Whole genome sequencing and comparative analysis of 3 LA-Kp and 3 non-LA-Kp identified 133 genes present only in LA-Kp. Further, large scale screening of the 133 genes in 45 LA-Kp and 103 non-LA-Kp genome sequences from public databases identified 30 genes that were highly associated with LA-Kp, includingiroBCD, iucABCDandrmpA/A2and 21 new genes. Then, these 21 new genes were analyzed in 40 LA-Kp and 86 non-LA-Kp clinical isolates collected in this study by PCR, showing that new genes were present 80-100% among LA-Kp isolates while 2-11% inK. pneumoniaeisolates from sputum and urine. Several of the 21 genes have been proposed as virulence factors in other bacteria, such as the gene encoding SAM-dependent methyltransferase andpagOwhich protects bacteria from phagocytosis. Taken together, these genes are likely new virulence factors contributing to the hypervirulence phenotype of hvKp, and may deepen our understanding of virulence mechanism of hvKp.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Ye
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Bioinformatics, SJTU-Yale Joint Center for Biostatistics, Shanghai Jiaotong University Shanghai, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: You
authors.affiliation: Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Yanliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Taohui
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Sixth Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Zuochun
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Chuxiao
authors.initials: C
authors.lastname: Shao
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Baixing
authors.initials: B
authors.lastname: Ding
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Fifth Affiliated Hospital of Wenzhou Medical University Lishui, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University Shanghai, China.
authors.forename: Minggui
authors.initials: M
authors.lastname: Wang
mesh_terms: D002681:China; D019295:Computational Biology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D005838:Genotype; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D008100:Liver Abscess / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D065288:Serogroup; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial; D037521:Virulence Factors
keywords: genome comparative analysis; hypervirulent Klebsiella pneumoniae; liver abscess; plasmid; virulence