Interação entre Lipoxina A4 (LXA4) e Padrões Moleculares Associados a Patógenos (PAMPs) de Streptococcus pneumoniae: análise in silico por bioinformática

Abstract

Streptococcus pneumoniae is a gram-positive diplococcus bacterium that colonizes the human nasopharynx and is one of the main causes of pneumonia. S. pneumoniae possesses various antigenic molecules, also considered Pathogen-Associated Molecular Patterns (PAMPs), such as pneumolysin, immunoglobulin A1 protease, zinc metalloprotease (ZmpC), pneumococcal surface adhesin A (PsaA), peptidoglycan N-acetylglucosamine deacetylase, which can trigger different types of immune responses. The lipid mediator Lipoxin A4 (LXA4) is derived from Arachidonic Acid (AA) and has been associated with specialized pro-resolving mediators (SPMs), considered over the past few decades as potential therapeutic targets related to improving the resolution of the inflammatory process. In this study, the general objective is to evaluate, in silico, the interaction between LXA4 and these PAMPs of the bacterium using bioinformatics platforms. The literature review was conducted through PubMed, Scielo, and Capes Journals. The UniProt, Protein Data Bank, Alphafold Protein Structure Database, LIPID MAPS, and KEGG databases were used to obtain the access codes for the targets and the ligand (LXA4), visualize the 3D protein structures of the PAMPs, analyze the lipid's chemical structure, and validate the LXA4 metabolic pathway. The molecular docking results showed hydrogen bonds and hydrophobic interactions between the ligand and the PAMPs. To validate the obtained interactions, molecular dynamics simulations were performed, showing stability and smooth fluctuations between LXA4 and ZmpC, pneumolysin, and IgA1 protease, suggesting that the lipid mediator may modify the structures and functions of these PAMPs, favoring and promoting the mechanisms of appropriate innate and humoral immune responses. To elucidate whether the interactions identified so far could positively interfere with the resolution of pneumonia by the bacterium, in vivo, in vitro or ex vivo experiments will be needed to validate the computational biology data obtained. Nevertheless, the present study provides new insights into the interaction between LXA4 and the described PAMPs of the pathogen,suggesting that the lipid mediator may play a positive role in the immune response against pneumonia induced by S. pneumoniae.