Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution
单位：[1]Peking Union Medical College, Instituteof Respiratory Medicine, ChineseAcademy of Medical Sciences, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,Laboratory of Clinical Microbiology andInfectious Diseases, China-JapanFriendship Hospital, Beijing, People’sRepublic of China[3]Institute of InfectiousDiseases, Beijing Ditan Hospital, CapitalMedical University and Beijing KeyLaboratory of Emerging InfectiousDiseases, Beijing, People’s Republic ofChina[4]Clinical Center for PulmonaryInfections, Capital Medical University,Beijing, People’s Republic of China[5]National Clinical Research Center ofRespiratory Diseases, Beijing, People’sRepublic of China[6]Tsinghua University-Peking University Joint Center for LifeSciences, Beijing, People’s Republic ofChina
Background: Multidrug-resistant (MDR) ST11 hypervirulent Klebsiella pneumoniae (hvKp) is emerging in China. Purpose: The aim of this study was to track the transmission and evolution of hvKp. Materials and Methods: A retrospective study focused on Kp infection was conducted. Clinical data were collected from electronic medical records. Whole-genome sequencing of Kp strains was performed. Single-nucleotide polymorphisms (SNPs) were analyzed and a transmission map was constructed. Sequence type, and antimicrobial and virulence-associated genes were characterized. Strains with some combination of the virulence genes, (p)rmpA, (p)rmpA2, iucA, iroB, and peg-344, were defined as hvKp. Kp virulence phenotypes were evaluated using the Galleria mellonella model. Results: All 33 Kp strains were MDR-Kp and 13 (39.4%) were hvKp. Most hvKp strains (84.6%, 11/13) were hospital-acquired infections (HAIs). Two unique combinations of virulence-associated genes were detected among hvKp strains. Eleven cases were associated with (p)rmpA2+iucA and two strains presented with peg-344+(p)rmpA+(p)rmpA2+iucA. Surprisingly, two community-acquired MDR-hvKp infection cases were identified. Eight hvKp strains (61.5%, 8/13) exhibited a hypervirulent phenotype in the G. mellonella model. Five MDR-hvKp strains with the hypervirulence phenotype originated from a single cluster. Additionally, nine clones were identified among the two clades, six of which were hvKp. Moreover, the hvKp in clade 1 carried the IncHI1B plasmid replicon, whereas none of the hvKp strains in clade 2 harbored IncHI1B. These data, showing that different hvKp clones distributed into separate clades, indicate that transmission and evolution occurred within the hospital. Conclusion: During inter-host evolution and transmission, various virulence clusters of the epidemic clone, MDR-ST11, converged, conferring phenotypic virulence heterogeneity and spread within the hospital and possibly the community. Mobile/conjugative genetic elements associated with virulence-encoding gene clusters might emerge and have been transmitted within the hospital, suggesting that enhanced ongoing surveillance is essential.
基金：
Peking Union Medical College Graduate Innovation Foundation [2018-1002-01-25]; CAMS Innovation Fund for Medical Sciences [CIFMS 2018-I2M-1-003]; National Science Grant for Distinguished Young Scholars [81425001/H0104]
第一作者单位：[1]Peking Union Medical College, Instituteof Respiratory Medicine, ChineseAcademy of Medical Sciences, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,Laboratory of Clinical Microbiology andInfectious Diseases, China-JapanFriendship Hospital, Beijing, People’sRepublic of China
通讯作者：
通讯机构：[1]Peking Union Medical College, Instituteof Respiratory Medicine, ChineseAcademy of Medical Sciences, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,Laboratory of Clinical Microbiology andInfectious Diseases, China-JapanFriendship Hospital, Beijing, People’sRepublic of China[4]Clinical Center for PulmonaryInfections, Capital Medical University,Beijing, People’s Republic of China[5]National Clinical Research Center ofRespiratory Diseases, Beijing, People’sRepublic of China[6]Tsinghua University-Peking University Joint Center for LifeSciences, Beijing, People’s Republic ofChina
推荐引用方式(GB/T 7714)：
Chao Liu,Pengcheng Du,Jiankang Zhao,et al.Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution[J].INFECTION and DRUG RESISTANCE.2020,13:1713-1721.doi:10.2147/IDR.S243836.
APA：
Chao Liu,Pengcheng Du,Jiankang Zhao,Binbin Li,Chunlei Wang...&Bin Cao.(2020).Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution.INFECTION and DRUG RESISTANCE,13,
MLA：
Chao Liu,et al."Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution".INFECTION and DRUG RESISTANCE 13.(2020):1713-1721
