Mygalin interaction with immune cells and infection control by pathogenic microorganisms

• Grant number: 20/08182-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Monamaris Marques Borges
• Grantee: Monamaris Marques Borges
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Marcia Regina Franzolin ; Pedro Ismael da Silva Junior
• Associated scholarship(s): 23/08292-2 - Impact of mygalin interaction on the inflammatory response induced by TLR3 agonists, BP.TT; 23/07457-8 - Action of Mygalin in the control of in vitro infection of macrophages and epithelial cells by bacteria., BP.TT; 22/05535-9 - Action of Mygalin in the control of in vitro infection of macrophages and epithelial cells by bacteria., BP.TT

Abstract

The discovery of new bioactive molecules to help control infections by bacteria resistant to antibiotics, as well as immunomodulatory, is extremely necessary. The exploration of biodiversity as a source of products with therapeutic potential is an alternative to combat infections, immune modulation or treatment of other pathologies. Polyamines are a group of endogenous cationic compounds synthesized by all living cells. They influence several cellular functions since they bind to DNA, RNA, and proteins, controlling the growth, differentiation and survival of microorganisms and eukaryotic cells. Its analogues have been widely explored in the control of microorganisms, immune functions and cancer. Mygalin is a synthetic acyl polyamine similar to the natural polyamine spermidine and originates from spider hemolymph. This molecule differs from spermidine since it has microbicidal activity, causing disruption of the bacterial wall, DNA damage, in addition to modulating the innate immune response. These characteristics show that this molecule represents a therapeutic target to be explored against microorganisms resistant to antibiotics and its role as an immune regulator. The action of Mygalin in the interaction with phagocytic cells treated with molecules originating from microorganisms represented by agonists of Toll-like receptors (2,3 and 9) in the presence or not of cytokines and inhibitors of intracellular signal pathways, MAPKinases and NFkB will be investigated, to define its potential to modulate the inflammatory response. Its ability to control the synthesis of immune mediators in cells infected in vitro by gram negativa bacteria, as well as biofilm formation when associated with antibiotics or silver nanoparticles, will be investigated. (AU)