A new anti-virulence strategy against pathogenic bacteria: Targeting spreading factors

The widespread use of antibiotics against bacterial pathogens has caused a surge in the emergence of drug resistant strains. Treating infections caused by drug resistant bacteria costs on average twice as much compared to their drug-susceptible counterparts, and is a burden on the economy and the healthcare system. A promising strategy is the anti-virulence approach, which targets bacterial pathogenicity, thereby facilitating clearance of the infection without pressuring the pathogen to become resistant. Here, we propose to target the enzyme hyaluronidase as an anti-virulence approach against bacterial pathogens such as Staphylococcus aureus and Streptococcus agalactiae. Hyaluronidase is an enzyme responsible for degrading hyaluronan in the body and contributes to bacterial growth and penetration. We have designed a mass spectrometry-based assay that can directly assess the anti-hyaluronidase activity of extracts and pure compounds. Additionally, we have identified several endophytic fungal species isolated from the roots of Anemopsis californica, a botanical used to treat skin infections, which produce compounds that inhibit hyaluronidase. This presentation will include the results of bioassay-guided fractionation experiments aimed at identifying hyaluronidase inhibitors from A. californica endophytes using the new assay.