Pseudomonas aeruginosa Bacteriophages
Antimicrobial Activity of Bacteriophages and Their Lytic Products in Respect to Pseudomonas aeruginosa Clinical Isolates
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- MED-DRG/Drug Discovery/Medicine
3 Approved without Funding
State Scientific Center of Genetics and Selection of Industrial Microorganisms (GosNIIGenetica), Russia, Moscow
- Institute of Immunological Engineering, Russia, Moscow reg., Lyubuchany
- Queen's University, Department of Microbiology and Immunology, Canada, ON, Kingston\nThe Evergreen State College, USA, MD, Washington\nUniversity of Turku / Finnish-Russian Joint Biotechnology Laboratory, Finland, Turku\nLaval University, Canada, QC, Quebec City
Project summaryThe aim of the Project – a search for new phages and their lytic products possessing activities against Pseudomonas aeruginosa clinic isolates.
Perennial use of antibiotics leads to a multi-drug resistance of many pathogenic bacterial strains. As the result, a search for new approaches to the therapy of bacterial infections is is being sought. One of such approaches is phagotherapy: the use of bacterial viruses (bacteriophages, phages).
Ideally in phagotherapy, with live phages, a mixture of truly virulent phages with a broad spectrum of lytic activity is used. One of the causes of the destruction of pathogenic bacteria using phages is the action of lytic products formed by the phages. Obtaining and using such phage lytic products presents a second approach enhancing phagotherapy efficacy. In order to obtain new lytic products with a widened spectrum of activity against various pathogenic bacteria, it is necessary to have new bacteriophages with unique spectra of lytic activity. A selection of such phages could be performed using natural (clinical) phage stable variants of bacteria or using especially selected mutants of model bacterial strains with multiple phage stability. The genome of such phages is a valuable source for the cloning of protein-enzyme genes with unique lytic properties. Lytic enzymes are unified under the general term «endolysins or lysins», though the chemical mechanisms of their action may be different. Moreover, even lytic enzymes, of different phage species, possessing similar mechanisms of action could possess different physico-chemical properties that may be critical for the preparation of the end product. Among the phages as possible sources of genes of lysozyme-like proteins, P. aeruginosa phages are of special interest. Primarily, they are extremely persified in species level. P. aeruginosa is a highly relevant pathogen since it possesses extremely high antibiotic resistance and is the agent of a number of serious infections or complications (post-burn infections, wound infections). Lung infection in patients with cystic fibrosis is of special importance. That is why the treatment of these diseases using phagotherapy could be of significant benefit in a number of cases in comparison with other approaches.
In the proposed work, a search for new phage species active against P. aeruginosa will be undertaken for comparative genetic studies. This will be accompanied by cloning of genes controlling the synthesis of potentially interesting lytic product, their expression studied, and the properties of the products compared in order to detect of possible differences contributing their stability or medicinal application. Lytic products of a group of unique phages will be isolated, purified, and their activity will be studied in clinical isolates of Pseudomonas aeruginosa. A group of unique P. aeruginosa bacteriophages, the lytic products of which are still unstudied, but could be of interest for phagotherapy, are available for the project participants. Phages of several different species active for P. aeruginosa including gigantic phiKZ- like phages (Myoviridae), phages of KMV species (Podoviridae), temperate transposable phages belonging to 4 different species (D3112, B3, HW12 and PM681) (Siphoviridae) will be included into the work.