Advancing Treatment for Antibiotic-Resistant Infections with Enterococcus Pore-Forming Toxin Technology

Background

Enterococcus faecalis and Enterococcus faecium have emerged as significant contributors to multidrug-resistant (MDR) infections, posing a substantial threat to public health due to their inherent and acquired resistance to antibiotics. The unmet medical need involves addressing the high mortality rates associated with these difficult-to-treat infections. These bacteria also play roles in conditions such as alcoholic liver disease and immune response regulation to tumor antigens. While some bacterial toxins have been harnessed for therapeutic and cosmetic applications, the Enterococcus species are not known to express potent protein toxin families targeting human and animal cells. Current standard care relies heavily on antibiotics, which are increasingly ineffective against MDR strains, leaving a critical gap for innovative treatments that can overcome antibiotic resistance and efficiently target bacterial pathogens.

Technology Overview

The disclosed technology involves isolated and modified Enterococci toxin polypeptides, known as Epx, that form nanopores. These polypeptides are part of the uncharacterized small β-barrel pore-forming toxins (PFTs) from E. faecalis, E. faecium, and E. hirae. Identified as members of the haemolysin family, these toxins interact specifically with the human HLA-I and homologous MHC-I receptors of certain animal species, demonstrating selective toxicity. Epx nanopores present a novel mechanism for potential therapeutic applications, including the translocation of biological polymers and the possibility of use in adjuvants or vaccines. There is proof-of-concept data indicating that certain Epx variants mediate virulence by inducing cell death and damaging cellular structures, offering a targeted approach to treating diseases associated with MHC class I dysregulation.

Applications

• Treatment of antibiotic-resistant Enterococcus infections
• Use in vaccines targeting MHC class I-related diseases
• Development of biotechnological tools leveraging nanopore formation

Advantages

• Specific targeting of human and animal cell receptors, reducing off-target toxicity
• Potential role in overcoming antibiotic resistance
• Opportunities for novel vaccine and adjuvant development
• Ability to form pores for biological polymer translocation