Background:

Worldwide, the global emergence of multidrug-resistant (MDR) bacteria is a growing threat to public health. Acinetobacter baumannii is a Gram-negative bacterium causing nosocomial infections worldwide. According to WHO, this strain is considered today as the most dangerous MDR pathogen among the twelve deadliest drug-resistant bacteria. Therefore, new approaches for controlling this pathogen are urgently needed. Enzybiotics (i.e. enzyme-antibiotic) are lytic enzymes (also known as endolysins or lysins) that encoded by bacteriophages or prophages and can act as weapons in the fight against drug-resistant bacteria. Enzybiotics have received considerable attention as potential antibacterial agents because they show high specificity, are bactericidal (not just bacteriostatic), act in a short contact time to promote killing of bacterial pathogens and they do not develop resistance.

 

Aims:

Drawing from the fields of enzymology, microbiology and omics technologies, the proposed project will apply a multidisciplinary scientific approach for the:

(a) Identification and characterization novel lytic enzymes towards the human pathogen Acinetobacter baumannii by mining available bacteriophage and prophage genomes and metagenomics libraries (created from clinical and hot spring environmental samples) through bioinformatics

(b) Cloning, heterologous expression and functional characterization selected lytic enzymes;

(c)Engineering novel specificities and catalytic activities by modifying natural lytic enzymes through in vitro directed evolution and fusion technologies with antimicrobial peptides for enhancing their catalytic activity towards Gram-negative pathogens,

(d) Study and analysis of the structural and physicochemical properties of engineered endolysins, using differential scanning calorimetry, fluorimetry, molecular modeling and X-ray crystallography.

 

Beyond the direct impact on R&D activities, the completion of the project will offer the opportunity for:
 

i) Reinforcement of the academic capacity in the fields of pharmaceutical biotechnology by exchanging complementary information related to well specified targets, developing joint activities and strengthening the links between different academic partners. The project envisages the establishment of joint activities and the strengthening of links between different partners, and it will contribute towards the establishment of lasting collaborations. 
 

ii) Know-how diffusion: help researchers to be trained on modern interdisciplinary biotechnological areas related to biotechnology and health sciences and allow them to have access to modern techniques and methods. The project will contribute to the national capacity in key scientific priorities, in particular, the fields of enzyme technology and pharmaceutical biotechnology.