New synergistic strategy to treat chronic wound infections

Principal Investigator: Lidija Senerovic, PhD

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide, affecting 422 million people. It is estimated that the number of patients will double in the next 20 years. In 2015 in Serbia there were over 864.000 diagnosed DM patients and about 375.000 undiagnosed cases. Approximately 20–25% of DM patients will develop foot ulceration during the course of their disease. Up to a quarter of them will develop infections that will require amputation. Treatment of chronic wounds in DM patients has become extremely difficult due to infections caused by multidrug resistant organisms like antibiotic resistant Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus. Frequently, the cause of bacterial low sensitivity or resistance to antibiotics is their ability to form biofilms. Impaired healing in diabetic wounds is correlated with P. aeruginosa ability to form biofilms within the patients’ tissue(s).

The aim of this project is to discover novel drug leads for new antimicrobial agents targeting bacterial virulence and to develop new strategy for the efficient treatment of P. aeruginosa infections residing in chronic wounds including diabetic foot ulcers. The new drugs should exhibit anti-biofilm activity with low potential to develop resistance. Therefore, we will explore soil bacteria diversity for structurally new molecules and, based on structure-activity studies, derivatize selected anti-virulence drugs to improve their performance. The best candidate will be conjugated with novel two-component multifunctional nano-carriers to improve its therapeutic index and enable simultaneous bacterial biofilm disruption and clearance of deep tissue infection. This synergistic strategy is expected to provide effective therapy of difficult-to-treat chronic wound infections thus helping their timely healing.