Differential mucosal tropism and dissemination of classical and hypervirulent Klebsiella pneumoniae infection
Teck-Hui Teo,
Nurul N. Ayuni,
Michelle Yin,
Jun Hao Liew,
Jason Q. Chen,
Natalia Kurepina,
Ravisankar Rajarethinam,
Barry N. Kreiswirth,
Liang Chen,
Pablo Bifani
Affiliations
Teck-Hui Teo
Agency for Science, Technology and Research (A∗STAR), Infectious Diseases (ID) Labs, Singapore 429621, Singapore; Corresponding author
Nurul N. Ayuni
Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Michelle Yin
Agency for Science, Technology and Research (A∗STAR), Infectious Diseases (ID) Labs, Singapore 429621, Singapore
Jun Hao Liew
Agency for Science, Technology and Research (A∗STAR), Infectious Diseases (ID) Labs, Singapore 429621, Singapore; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Jason Q. Chen
Agency for Science, Technology and Research (A∗STAR), Infectious Diseases (ID) Labs, Singapore 429621, Singapore
Natalia Kurepina
Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ 07110, USA
Ravisankar Rajarethinam
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore 138673, Singapore
Barry N. Kreiswirth
Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ 07110, USA
Liang Chen
Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ 07110, USA
Pablo Bifani
Agency for Science, Technology and Research (A∗STAR), Infectious Diseases (ID) Labs, Singapore 429621, Singapore; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E7HT, UK; Corresponding author
Summary: Klebsiella pneumoniae (Kp) infection is an important healthcare concern. The ST258 classical (c)Kp strain is dominant in hospital-acquired infections in North America and Europe, while ST23 hypervirulent (hv)Kp prevails in community-acquired infections in Asia. This study aimed to develop symptomatic mucosal infection models in mice that mirror natural infections in humans to gain a deeper understanding of Kp mucosal pathogenesis. We showed that cKp replicates in the nasal cavity instead of the lungs, and this early infection event is crucial for the establishment of chronic colonization in the cecum and colon. In contrast, hvKp replicates directly in the lungs to lethal bacterial load, and early infection of esophagus supported downstream transient colonization in the ileum and cecum. Here, we have developed an in vivo model that illuminates how differences in Kp tropism are responsible for virulence and disease phenotype in cKp and hvKp, providing the basis for further mechanistic study.
