Research On The Effect And Mechanism Of Antimicrobial Peptides HPRP-A1/A2 Work Against Toxoplasma Gondii Infection

With increasing antibiotics resistance and drug safety,there is an urgent need for novel therapeutics for Toxoplasma gondii.Antimicrobial peptides(AMPs)are promising candidates that could address the spread of multidrug-resistant pathogen.HPRP-A1 and HPRP-A2 are known to display the antimicrobial activity against gram-negative bacteria,gram-positive bacteria,as well as some pathogenic fungi;however,the role of HPRP-A1 and HPRP-A2 on Toxoplasma gondii,an obligate intracellular protozoan,is still unknown.In this study,we evaluated the antimicrobial efficacy and mechanism of these two antimicrobial peptides on Toxoplasma gondii in mice in vivo and in vitro.Trypan blue was used to stain tachyzoites to evaluate the antimicrobial efficacy.Electron microscopy,flow cytometry and RT-PCR were conducted to study the mechanism.Both HPRP-A1 and HPRP-A2 treatment made more tachyzoites stained blue than untreatment.HPRP-A1 and HPRP-A2 treatment damaged the integrity of tachyzoites membrane,characterized by membrane disorganization and cytoplasm outflow of tachyzoites.Injection with HPRP-A1 and HPRP-A2 showed a significant decreased number of tachyzoites in Toxoplasma gondii-infected mice.Furthermore,HPRP-A1 and HPRP-A2-treated splenocytes exhibited a significant increase in Tc1 and Th1 response,HPRP-A1 and HPRP-A2-stimulated macrophages inhibited the growth of CFSE-labeled tachyzoites,which were accompanied by inducing higher mRNA levels of TNF-? and IL-12 production.Taken together,these results implicate both HPRP-A1 and HPRP-A2 are effective against Toxoplasma gondii through damaging the membrane of tachyzoites and inducing protective immune response,which would offer an alternative approach for the treatment of Toxoplasma gondii infection.