Study of microencapsulated biomodulators with antimicrobial and antivirulence activities in multi-drug resistant uropathogenic Escherichia coli strains

Abstract

Urinary tract infections are frequent worldwide, with Uropathogenic Escherichia coli (UPEC) being the pathogen responsible for 75% of these cases. In April 2019, the WHO and the UN published an article on the need for the development of new substances capable of combating infections caused by Multi-Drug Resistant bacteria (MDR), placing MDR UPECs on the priority pathogen list. The search for new molecules capable of combating infections caused by these microorganisms can be based on studies by the search for new molecular targets for drug action. Bacteria communicate with their environment through chemical signaling molecules that favor the process of colonization and establishment of pathogenesis. One of the systems responsible for detecting these molecules is composed of a membrane sensing protein (QseC) and another cytoplasmic response regulator (QseB), constituting the Two-Component System (TCS) QseBC, capable of recognizing in the environment signals produced by the host and by other bacteria, leading to regulation of pathogen virulence gene expression. Studies conducted by our group showed attenuation of the virulence of Gram-negative pathogens in the absence of the qseC gene, leading to the development of molecules that act by inhibiting this pathway, such as LED209. The objective of the present project is to study, through the construction of already characterized TCS gene mutants, the alterations in the virulence profile of these pathogens, in order to qualify these systems as molecular targets for the development of biomodulatory molecules that exert antimicrobial and anti-virulence activities. MDR UPECs, as well as LED209 microencapsulation to circumvent the solubility problem. (AU)