TECHNOLOGY

Imagine if antibiotics worked against complicated infections such as prosthetic joint infections, endocarditis, and osteomyelitis, and common infections were cured more quickly and effectively. 

This should be possible for the first time since Arietis is developing novel proprietary antibiotics that activate the ClpP protease and cause cells to self-digest. This unique “activating” mechanism causes rapid and exceptional killing of the highly resistant “ESKAPE” pathogens Staphylococcus aureus and Enterococcus faecium, as well as the leading cause of acute bacterial respiratory infections, Streptococcus pneumoniae.    

Killing by ClpP activation is effective against even non-growing cells, in contrast to other antibiotics, which target processes that are inactive in non-growing cells. Many bacteria can evade killing by traditional antibiotics, even surviving high concentrations for prolonged periods, by simply growing slowly or not at all. These survivors contribute to antibiotic resistance, cause recurrent infections, and explain why traditional antibiotics are unable to kill biofilms, which have restricted access to the immune system.  

However, bacteria cannot escape death by shutting down or waiting until antibiotic levels drop when ClpP is activated. Combining ClpP activators with traditional antibiotics prevented resistance development and caused eradication of MRSA infections in animal models where traditional antibiotics failed due to biofilms. This strategy may allow complicated infections to be cured with antibiotics for the first time and common infections to be treated more quickly and effectively with less recurrence.

It is important not to overlook the ongoing threat of antimicrobial resistance in Gram positive pathogens:

• There are more deaths in the US from infections caused by drug resistant gram positive pathogens (MRSA, VRE and drug resistant S. pneumoniae) compared to the gram negatives (carbapenem-resistant Enterobacteriaceae, multidrug-resistant Pseudomonas and Acinetobacter).
• There is still a high unmet need for novel antibiotics to treat drug resistant Gram positive infections especially for complicated infections such as endocarditis, osteomyelitis, diabetic ulcers, prosthetic joint and catheter related infections.