SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE

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Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35

Suyeon Park, Hyunkeun Kim, Kwan Soo Ko

Journal of Biomedical Science
Klebsiella pneumoniae is one of the significant gram-negative pathogens that cause a variety of diseases including intra-abdominal infections, pneumonia and urinary tract infections. Due to the increased antimicrobial resistance in K. pneumoniae, tigecycline is often used as a last-resort antibiotic to multidrug-resistant K. pneumoniae. However, tigecycline resistance has been reported with increased frequency in K. pneumoniae.
In this study, we investigated the mechanisms that link tigecycline susceptibility to decreased virulence. Transcriptomic analyses demonstrated a significant decrease in the expression of ompK35 in the tigecycline resistant mutants. We observed that tigecycline-resistant mutants overexpressed ompR, and that the expression of ompK35 was regulated negatively by ompR. While tigecycline-resistant mutants and ompR-overexpressed mutants exhibited reduced hypermucoviscosity and virulence, deletion of ompR from tigecycline-resistant mutants restored their hypermucoviscosity and virulence.
In the present study, we demonstrated that ompR expression is regulated by exposure to tigecycline, thereby affecting the virulence associated phenotypes in K. pneumoniae strains. This study was published in Journal of biomedical science in March 2023 (https://doi.org/10.1186/s12929-023-00910-w)