Novel quorum sensing inhibitors for anti-virulence treatment of skin infections caused by pathogenic Gram-positive bacteria

Grantee: Professor Christian Adam Olsen, Department of Drug Design and Pharmacology, University of Copenhagen

Grant:  2,110,500 DKK

Staphylococcal bacteria are the most common cause of skin and soft tissue infections (SSTI) and with the rise of methicillin-resistant Staphylococcus aureus (MRSA) minor infections can lead to severe medical conditions.

The increasing antibiotic resistance development demands the search for alternative medicines with differing profiles ranging from prophylactic treatment of small infections to combating life-threatening conditions.

In the present project, we aim to inhibit this quorum sensing through a novel concept and thereby develop pan-staphylococcal inhibitors that are capable of treating the virulence in skin infections without the use of antibiotics.

Targeting the virulence of a bacterial infection rather than the viability of the pathogen represents such an alternative, because it increases the chance of clearance through the human immune system and attenuates disease symptoms while minimizing the risk of emerging resistance.

The expression of virulence factors in Gram-positive bacteria, including staphylococci, is regulated through quorum sensing (QS), which is a mechanism that allows bacteria to change gene expression in response to cell density.

This cell-to-cell communication is mediated by the secretion and detection of molecules termed autoinducing peptides (AIPs).