Molybdate transporter ModABC contributes to Klebsiella pneumoniae muscle infection and new insight into its treatment

Abstract:

[Background] Klebsiella pneumoniae (Kp) is a major pathogen that causes nosocomial infections and community-acquired infections. In recent years, drug resistance in Kp has become more and more serious, making its treatment less effective. So it becomes a challenge in clinical treatment. At present, more unusual cases of pyomyositis caused by Kp have been reported. Infection in deep muscle may form an anaerobic environment. The molybdate transporter ModABC is essential for bacterial anaerobic nitrate respiration. Previous studies showed that ModA might be positively correlated with Kp virulence. [Objective] To investigate the effect of molybdate transporter ModABC on Kp muscle infection and the potential use of tungstate in treatment. [Methods] The modA traceless deletion mutant and complementary strain were constructed. Then the effect and mechanism of ModABC on Kp muscle infection were analyzed by monitoring anaerobic growth, nitrate reductase activity in vitro and mouse muscle infection experiments in vivo. The possibility and efficacy of tungstate treatment for Kp muscle infection were discussed in this study. [Results] The modA traceless deletion mutant and complementary strain were successfully constructed. This study found that deletion of modA led to significantly inhibited anaerobic growth of Kp and reduced nitrate reductase activity in vitro. The knockout strain ΔmodA showed greatly reduced muscle abscess, intramuscular growth and invasion in mouse muscle abscess model. In vitro tungstate treatment inhibited the anaerobic nitrate respiration of wild strain WT, and also significantly inhibited the growth of WT in muscle abscess model, but had no influence on strain ΔmodA. [Conclusion] The molybdate transporter ModABC contributes to Kp muscle infection by providing fitness advantage through enhancing invasiveness and promoting anaerobic nitrate respiration. Tungstate can reduce the fitness advantage conferred by ModA and has a certain therapeutic effect on Kp muscle infection. This study is helpful to elucidate the mechanism of molybdenum's effect on the pathogenicity of Kp. It also provides new insight into the treatment, laying a foundation for further studies, especially carbapenem-resistant hypervirulent Kp infection.