Use of probenecid as an Anti-Virulence Agent Against Listeria monocytogenes

This technology repurposes the FDA-approved drug small molecule as an anti-virulence agent to combat Listeria monocytogenes by reducing its pathogenicity while having minimal effects on bacterial growth under the tested in-vitro conditions..

Background:

Listeria monocytogenes is a harmful bacterium responsible for listeriosis, a serious infection that poses risks to humans and animals. Traditional antibiotic treatments focus on killing bacteria or inhibiting their growth, which can lead to antimicrobial resistance. There is a growing demand for alternative strategies that target bacterial virulence—the ability to cause disease—rather than bacterial survival itself. This approach aims to suppress infection severity while exerting less selective pressure than conventional antibiotics. The development of this technology addresses this unmet need by exploring the drug repurposing of an established compound to safely and efficiently reduce bacterial pathogenicity.

Technology Overview:

This innovation involves the use of a small molecule, a well-known FDA-approved drug traditionally used for other medical purposes, as an anti-virulence agent targeting Listeria monocytogenes. Preliminary in vitro studies indicate that a small molecule attenuates virulence-associated phenotypes in Listeria monocytogenes while having minimal effects on bacterial growth under the conditions tested. The technology’s mechanism includes reducing the bacteria's hemolytic activity—the process by which they damage host cells—and interfering with their ability to persist within host cells. By targeting these specific pathogenic processes, small molecules diminish the bacteria’s ability to survive in phagocytic immune cells, effectively disarming them rather than destroying them. Because small molecules are already approved drugs with a well-understood safety profile, this approach offers a faster development and translational pathway for new infectious disease therapies. The technology also proposes using small molecules and their analogs in combination with traditional antibiotics to enhance treatment effectiveness while potentially reducing the development of resistance.

Advantages:

•    Anti-virulence approach: Targets bacterial pathogenicity without inhibiting growth, reducing selective pressure for resistance.
•    Drug repurposing: Utilizes an FDA-approved medication; therefore, existing pharmacology and human-safety information may provide advantages for subsequent development.Reduction in bacterial virulence factors: Suppresses genes linked to invasion and intracellular survival, decreasing disease severity.
•    Potential adjunct therapy. May be evaluated in combination with standard antibiotic therapy.
•    Broad application potential: Useful in both human medicine and veterinary or food safety contexts to manage listeriosis.
•    Well-characterized safety profile: Prior human-use and pharmacology data may inform evaluation for a new indication.

Applications:

•    Treatment of listeriosis infections in humans by reducing bacterial virulence.
•    Adjunctive therapy alongside antibiotics to enhance efficacy and limit resistance emergence.
•    Veterinary medicine applications to control L. monocytogenes infections in animals.
•    Research tool to study virulence mechanisms and develop new anti-infective strategies.

Intellectual Property Summary: Patent pending

Stage of Development: TRL 3 (early proof of concept)

Licensing Status: This technology is available for licensing.

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