Infection and Drug Resistance (Jun 2020)
Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution
Abstract
Chao Liu, 1, 2 Pengcheng Du, 3 Jiankang Zhao, 2 Binbin Li, 2 Chunlei Wang, 2 Lingxiao Sun, 2, 4 Binghuai Lu, 2 Yimin Wang, 2 Yingmei Liu, 2 Bin Cao 1, 2, 4– 6 1Peking Union Medical College, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, People’s Republic of China; 4Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, People’s Republic of China; 5National Clinical Research Center of Respiratory Diseases, Beijing, People’s Republic of China; 6Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, People’s Republic of ChinaCorrespondence: Bin Cao Tel +86 10-84205288Email [email protected]: 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, prmpA, prmpA2, 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 prmpA2+iucA and two strains presented with peg-344+prmpA+prmpA2+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.Keywords: hypervirulent Klebsiella pneumoniae, multidrug resistance, whole-genome sequencing, hospital-acquired infection, community-acquired infection
