CHARACTERIZATION OF NUTRIENT UPTAKE MECHANISMS OF RESISTANT BACTERIA AND SEARCH FOR INHIBITORS USING BIOINFORMATICS

Acinetobacter baumannii and Klebsiella pneumoniae are gram-negative pathogens known for their antibiotic resistance, employing mechanisms of cellular communication and nutrient uptake mediated by ABC transporters. The substrate-binding proteins (SBPs) of these transporters play a crucial role in transport across the membrane and the absorption of nutrients, such as polyamines and taurine, which are essential for bacterial survival. This study aimed to characterize and predict the structures of SBPs that transport taurine and polyamines, as well as evaluate potential interactions with ligands and inhibitors. The FASTA sequences of PotD and TauA from A. baumannii, as well as PotD, PotF, and TauA from K. pneumoniae, were obtained from databases and analyzed using specific software to predict structure and interactions. Molecular docking performed on three-dimensional models of the proteins revealed favorable free energy for the binding of the proteins to their respective ligands, corroborating data from the literature; in particular, PotF from K. pneumoniaewas identified as a dual transporter of putrescine and spermidine. Additional tests showed that vigabatrin and GABA have the potential to interact with the TauA proteins, while cystamine was found to interact with PotD from A. baumannii. These results highlight the feasibility of using these molecules as targets to inhibit nutrient uptake in resistant bacteria, paving the way for the development of new antimicrobials. Identifying these interactions may open new avenues for treating infections caused by these pathogens, contributing to more effective therapeutic strategies in combating bacterial resistance.