The research to establish new therapeutic strategies for refractory hvKP infections

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16650
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Osaka Metropolitan University (2022); Osaka City University (2019-2021)
• Principal Investigator: Namikawa Hiroki 大阪公立大学, 大学院医学研究科, 講師 (60813417)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 高病原性肺炎桿菌 / RFP / rpoB

Outline of Final Research Achievements

We aimed to determine whether RFP exerts this effect at sub-growth-inhibitory concentrations via its binding to RpoB. Five spontaneous RFP-resistant mutants (R1～5) were prepared from an hvKP clinical isolate and subjected to whole genome sequencing and mucoviscosity analyses. Subsequently, we created a rpoB mutant R6 and revertants with wild-type rpoB from R1～5 (named R1'～5'). We evaluated transcription levels of rmpA and the capsular polysaccharide polymerase gene magA and capsule thickness of R1～5 and R1'～5' grown without or with RFP. R1～5 all had non-synonymous point mutations in rpoB and were highly resistant to the bacte- ricidal effects and anti-mucoviscous activity of RFP. While the properties of R6 were similar to those of R1～5,the responses of R1'～5' to RFP were identical to those of the wild type. rmpA and magA transcription levels and capsule thickness correlated well with the mucoviscosity levels. RFP exerts anti-mucoviscous activity by binding to RpoB.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

RFPの粘性抑制作用はrpoBの機能抑制を介して生じるという仮説が強く裏付けられた。このことから難治性hvKP感染症に対する新たなる治療戦略の確立に向けてまた一歩前進したと考える。しかしながら、その作用機序やin vivoでの効果については、まだ多くの疑問が残されている。今後、さらに詳細な反応機構を解明し、RFPのユニークで有用な活性を利用した抗菌療法を開発することが必要である。