Investigation of bacteriophages and phage-derived enzyme activity against biofilm-embedded cells of multidrug resistant Acinetobacter baumannii

Principal Investigator: Dr Goran Vukotic, Faculty of Biology University of Belgrade 

Acinetobacter baumannii is considered one of the most insidious pathogens for which the development of new drug is considered a CRITICAL priority according to the last WHO report. A. baumannii is a prevalent cause of hospital acquired infections, which has increased dramatically worldwide, with Mediterranean countries (Italy and Serbia included) reporting among the highest percentages of invasive multi-drug resistant (MDR) isolates. Furthermore, the ability of A. baumannii strains to form biofilm on both biotic and abiotic surfaces plays a significant role in their persistence and relapse of infection, given that the treatment of biofilms of MDR A. baumannii is almost impossible with current therapies.

In the last decade, phages, natural viruses of bacteria, have re-emerged as a promising option for the treatment of infections due to MDR strains. The benefits of phage therapy are based in their high specificity for given bacterial hosts and in the ability to rapidly multiply at the expense of bacteria they kill, consequently proliferating in situ – i.e. at the exact site of infection. Pivotal role in this process is played by lysins, proteins produced by phages, which cleave cell wall of host bacterium eventually leading to cell death. In addition, some phages produce depolymerases, biofilm matrix-degrading enzymes, which expose sessile cells in deeper layers to phage attack. This feature can be additionally utilized to combine the application of phages with antibiotic therapy, in a way that depolymerases might break through polymeric matrix, thus facilitating antibiotic penetration and biofilm eradication.

The project will focus on the effect of phages and their enzymes on antibiofilm-embedded cells, either alone or in combinations with different classes of antibiotics. During the project new lytic bacteriophages will be characterized in detail (genome sequencing, life cycle parameters, TEM), and proteins of interest cloned, expressed and purified.