Study and characterization of antibacterial activities and mechanisms of action of compounds produced by microorganisms from MicroBioBank

Abstract

Antimicrobial resistance is a growing concern and is estimated to become the major cause of global death in the coming decades. Pathogens of clinical interest such as Acinetobacter baumannii and Pseudomonas aeruginosa are particularly worrisome due to their ability to develop resistance to multiple classes of antibiotics. In addition to these, agricultural pathogens such as Xanthomonas citri subsp. citri, the causal agent of citrus canker, is a major threat to citrus production, especially in Brazil. Studies suggest that metabolites from bacteria, fungi, and plants can be effective and sustainable alternatives for controlling bacterial diseases. This project aims to prospect metabolites produced by microorganisms from uncommon or extreme environments, which is part of the MicroBioBank project, to identify innovative biomolecules of interest for health and agribusiness. Extracts containing the most promising antibacterial bioactive compounds will be tested against three target bacteria (A. baumannii, P. aeruginosa, and X. citri) to evaluate their potential to inhibit bacterial growth (MIC/MBC), to determine their killing times (time-kill curves), their ability to induce resistance, and potential action on biofilm formation. Subsequently, isolated bioactive compounds will be produced on a large scale to confirm their chemical structures and to determine their mechanisms of action, such as interference with some known cellular pathways (cell division, chromosome segregation, and cell wall synthesis), inhibition of macromolecule synthesis, and/or using RNA-seq. The discovery of new antibacterial agents will contribute to the development of effective antibiotics against resistant pathogens of clinical and agronomic interest.