Inhibition ofKlebsiella pneumoniaeGrowth and Capsular Polysaccharide Biosynthesis byFructus mume

Abstract

Klebsiella pneumoniaeis the predominant pathogen isolated from liver abscess of diabetic patients in Asian countries. With the spread of multiple-drug-resistantK. pneumoniae, there is an increasing need for the development of alternative bactericides and approaches to block the production of bacterial virulence factors. Capsular polysaccharide (CPS), especially from the K1 and K2 serotypes, is considered the major determinant forK. pneumoniaevirulence. We found that extracts of the traditional Chinese medicineFructus mumeinhibited the growth ofK. pneumoniaestrains of both serotypes. Furthermore,Fructus mumedecreased the mucoviscosity, and the CPS produced in a dose-dependent manner, thus reducing bacterial resistance to serum killing. Quantitative reverse transcription polymerase chain reaction analyses showed thatFructus mumedownregulated the mRNA levels ofcpsbiosynthesis genes in both serotypes, possibly by increasing the intracellular iron concentration inK. pneumoniae. Moreover, citric acid, a major organic acid inFructus mumeextracts, was found to have an inhibitory effect on growth and CPS biosynthesis inK. pneumoniae. Taken together, our results indicate thatFructus mumenot only possesses antibacterial activity against highly virulentK. pneumoniaestrains but also inhibits bacterial CPS biosynthesis, thereby facilitating pathogen clearance by the host immune system.