Use of phage endolysins with membrane permeabilizer agents against multi-resistant gram-negative bacteria: a strategy for antibacterial therapy

Abstract

Gram negative bacteria has a complex morphology, composed of a plasma membrane and a cell wall, that are composed of a thin layer of peptidoglycan and a lipopolysaccharide outer membrane, which makes them relatively more resistant to drugs and bactercidal agents. In such context, with the increase in the use of antibiotics, bacteria have developed multidrug resistance. The multidrug resistance of pathogenic bacteria to antibiotics has become a major concern in modern times. This process is natural and occurs due to the selective pressure created by the use of antibiotics, having been accelerated by the exacerbated and inappropriate use. Consequently, a new strategy is required for this therapy, which arises with the use of phage. enzymes, endolysins. The target of action of these enzymes is peptidoglycan, a structure that maintains the integrity of the cell, which when hydrolyzed results in cell death. Even though, researchs have shown that the outer membrane is the pricipal barrier against the exogenous application of endolysins, as it is lipopolysaccharide and has low permeability to these enzymes. Thus, the present project aims to evaluate the antimicrobial activity of phage endolysin enzymes, produced in the lytic cycle, against multidrug-resistant Gram-negative bacteria, which will occur with enzymes available in the laboratory in the in vitro and in vivo models of Galleria mellonella, comparing the efficiency in the presence and absence of external membrane permeabilizing agents, having a great contribution in areas of clinical interest and contributing to the implementation of antibacterial therapies of multidrug-resistant pathogens, with great scientific impact for the country. This project is part of the Marco Túlio Pardini Gontijo master's degree project.