Estudo estrutural e avaliação do efeito antibacteriano de três lectinas de algas marinhas vermelhas da família OAAH em combinação com antibióticos

Abstract

Lectins are proteins that recognize and bind to carbohydrates and glycoconjugates in a reversible manner. Due to their specificity for carbohydrates, these molecules can present a variety of interesting properties for the areas of biotechnology and biomedicine, such as antiviral, antibacterial and antitumor activities. There is currently a global urgency to bioprospect new molecules capable of combating resistant bacteria, which represent a serious problem for public health. In the present work, three lectins from red marine algae belonging to OAAH family (Oscillatoria agardhii agglutinin homologue), Amansia multifida (AML), Meristiella echinocarpa (MEL) and Solieria filiformis (SfL), were purified through ion-exchange chromatography in a DEAE-Sephacel matrix and the antibacterial potential of these lectins was evaluated. by the checkerboard method, together with oxacillin and tetracycline, against the strains Escherichia coli ATCC 11303, Staphylococcus aureus ATCC 25963 and S. aureus ATCC 700698 (MRSA). Three-dimensional models of AML and MEL were also constructed in silico and analyzed for the possible carbohydrate recognition site. Three-dimensional modeling of lectins revealed that, in general, they resemble β-barrel structures, with about 10 antiparallel strands on each chain, common in lectins of the OAAH family. By predicting of the binding sites, it was found that the amino acids that interact with carbohydrates are located at positions W145, R230, E258 and I261 for AML and W144, R229, E257 and I260 for MEL. According to the phylogenetic tree constructed based on their primary structure, MEL and SfL are well grouped among the lectins of the OAAH family, but AML is closer to the lectins of bacterial and cyanobacterial precursors of the family. AML, MEL and SfL together with oxacillin exhibited antagonistic interaction or no interaction with the antibiotic against the strains tested. However, AML and MEL exhibited a synergistic effect in conjunction with tetracycline against S. aureus ATCC 25963, in addition to an additive effect against MRSA and E. coli ATCC 11303. SfL together with tetracycline exhibited synergistic effect and additive effect against S. aureus ATCC 25963 and MRSA, respectively. We verified the antibacterial potential that lectins from the OAAH family have in combating resistant bacteria, in combination with tetracycline. Further studies are needed to understand how the interaction between proteins and antibiotics occurs.