2019年8月
Discovery of anti-mucoviscous activity of rifampicin and its potential as a candidate antivirulence agent against hypervirulent Klebsiella pneumoniae.
International journal of antimicrobial agents
- 巻
- 54
- 号
- 2
- 開始ページ
- 167
- 終了ページ
- 175
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.ijantimicag.2019.05.018
A recent increase in the incidence of hypervirulent Klebsiella pneumoniae (hvKP) infections, especially those caused by a sublineage of clonal group CG23 (CG23-I), is raising serious health concerns worldwide. The high virulence of hvKP is, at least in part, attributed to the overproduction of capsular polysaccharide (CPS), which is triggered by a positive regulator of capsular polysaccharide synthesis (cps) genes, named rmpA (regulator of mucoid phenotype A). Although extensive research has been conducted on the mechanisms of hvKP virulence, no study has focused on the development of antivirulence therapeutics. This study attempted to identify and validate an antimicrobial agent able to suppress hvKP hypermucoviscosity. A total of 18 commercially available antimicrobial agents, including β-lactams, quinolones and aminoglycosides, were tested. Rifampicin (RFP) was found to have strong anti-mucoviscous activity against CG23-I hvKP even at subinhibitory concentrations. Polysaccharide extracts from hvKP showed substantially lowered viscosity when cells were grown with RFP. Moreover, microscopic observations demonstrated that RFP treatment results in a drastic reduction in the thickness of the CPS layer around hvKP cells. RFP treatment decreased transcript levels of rmpA and rmpA-regulated cps genes, indicating that RFP suppresses mucoviscosity of hvKP through inhibition of rmpA transcription. These data suggest that RFP may serve as a potential antivirulence agent for refractory hvKP infection.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.ijantimicag.2019.05.018
- ISSN : 0924-8579
- PubMed ID : 31173862