Abstract
Antipathogenic compounds that target the virulence of pathogenic bacteria rather than their viability offer a promising alternative approach to treat infectious diseases. Using extracts from 30 Chinese herbs that are known for treating symptoms resembling infections, we identified an active compound falcarindiol from Notopterygium incisum Ting ex H. T. Chang that showed potent inhibitory activities against Pseudomonas aeruginosa multiple virulence factors. Falcarindiol significantly repressed virulence-related genes, including the type III secretion system (T3SS); quorum sensing synthase genes lasIR and rhlIR; lasB; motility-related genes fliC and fliG; and phenazine synthesis genes phzA1 and phzA2. P. aeruginosa swarming motility and pyocyanin production were reduced significantly. In a burned mouse model, falcarindiol treatment significantly reduced the mortality in mice infected with P. aeruginosa, indicating that falcarindiol is a promising antipathogenic drug candidate for treating P. aeruginosa infections.
Highlights
Antibiotic resistance in pathogenic bacteria has become one of the biggest threats to human health that we face today
We present data showing that falcarindiol significantly inhibited a broad range of important virulence factors in
In the initial screening for virulence inhibitors, we tested the effect of 30 herbal medicines known for the functions of “Qing Re Jie Du” [21], a term equivalent to “lowering fever and alleviating toxicity”
Summary
Antibiotic resistance in pathogenic bacteria has become one of the biggest threats to human health that we face today. Antibiotic resistance threatens to severely limit our ability to treat infectious diseases and our ability to perform various medical procedures, such as surgeries, tissue transplants, and cancer treatments [1]. All these procedures require preventing bacterial infections and the use of antibiotics are the only option. There is an urgent need to devise new therapeutic options for the treatment of infections caused by drug-resistant pathogens. Even though we are rapidly running out of effective antibiotics to treat infections, for Gram-negative bacteria, the search for new and potent antibiotics has been unsuccessful to date. Innovative approaches are needed to find new and effective antimicrobial therapeutics
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