Pesquisa de proteínas líticas fágicas e formulações lipossomais para a sua entrega a Helicobacter pylori

Abstract

Due to the increased antibiotic resistance of Helicobacter pylori, it is necessary to develop alternative strategies for its eradication, for example, the phage therapy, where it is possible to use phage lytic proteins. Some of the H. pylori prophage genomes integrate lytic genes, such as lysin or holin. 176 H. pylori strains were analysed to determine the presence of the gene coding for holin, which is usually located close to the lysin gene. This strategy has revealed the presence of holin in 32.4 % of the analysed strains, and from these, 87.7 % were also positive for the presence of integrase, the statistical association of this variables was verified. These results suggest the presence of phage lytic genes. The bacterium H. pylori is Gram-negative and therefore the peptidoglycan is covered with an outer membrane, preventing lysin to act on peptidoglycan. To overcome this barrier, liposomal formulation with different compositions were developed to find one that is more efficient in fusing with the outer membrane of H. pylori and release their contents (drugs or lysin) into the periplasmic space. A microbiology assay to determine the MIC of vancomycin and lysozyme in free form and encapsulated in two liposomal formulations was made. The results from the MIC determination and observation of the TEM images suggest that liposomes may be suitable for drug delivery to the periplasmic space of H. pylori.

Date of Award	2014
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Ana Filipa Vale (Supervisor) & Manuela Carvalheiro (Co-Supervisor)