- 作者: Suyeon Park, Hyunkeun Kim & Kwan Soo Ko
- 作者服務機構: 1.Department of Advanced Bioconvergence Product, Ministry of Food and Drug Safety, Cheongju, 28159, Republic of Korea 2.Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea
- 中文摘要:
- 英文摘要:
Background
The development of tigecycline resistance in hypervirulent Klebsiella pneumoniae strains has resulted in decreased virulence that is associated with reduced production of capsular polysaccharides (CPS). In this study, we investigated the mechanisms that link tigecycline susceptibility to decreased virulence.
Methods
We compared transcriptomes from tigecycline-susceptible wild-type strains and tigecycline-resistant mutants using mRNA sequencing. ompR-overexpressed and ompR-deleted mutants were constructed from wild-type strains and tigecycline-resistant mutants, respectively. Antibiotic susceptibility tests were performed, and string tests and precipitation assays were conducted to identify phenotypic changes related to tigecycline susceptibility and ompR expression. Bacterial virulence was assessed by serum resistance and Galleria mellonella infection assays.
Results
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.
Conclusions
In hypervirulent K. pneumoniae strains, ompR expression, which is regulated by exposure to tigecycline, may affect the production of CPS, leading to bacterial virulence. - 中文關鍵字:
- 英文關鍵字: Klebsiella pneumoniae, Tigecycline, ompK35, ompR, Hypermucoviscosity