Virulence inhibitors
Bacterial pathogens utilize a variety of tools to establish successful infections. These include a plethora of toxins, the formation of thick slimy biofilms, endotoxic lipopolysaccharides in the bacterial outer membrane, elastases that break down host connective tissue and flagellar motility, collectively referred to as bacterial virulence factors. The widespread use of, and dependence on, antibiotics to attempt to treat bacterial infections has inadvertently resulted in a strong rise in global encounters of drug resistance. Added to this, antibiotic-mediated killing of bacteria can also result in a massive sudden release of virulence factors, resulting in clinical deterioration of the patient. This has sparked interest in treatments that prioritize the targeting of bacterial virulence factors over bacterial killing.
We have discovered a group of therapeutics that interacts with two virulence factors simultaneously through a completely novel and not previously described Dual mechanism of Action. Both the mechanisms effectively target the bacterial virulence arsenal and collectively the dual functionality leads to a significantly reduced inflammation caused by pathogens in human epithelial cells. The treatment is highly effective against the clinically relevant Pseudomonas aeruginosa and Acinetobacter baumannii strains, including extensively antibiotic resistant clinical isolates.
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