Research on the effect and mechanism of antimicrobial peptides HPRP-A1/A2 work against Toxoplasma gondii infection

With increasing antibiotic resistance and drug safety concerns, novel therapeutics are urgently needed. Antimicrobial peptides are promising candidates that could address the spread of multidrug-resistant pathogens. HPRP-A1/A2 are known to display antimicrobial activity against gram-negative bacteria, gram-positive bacteria and some pathogenic fungi, but whether HPRP-A1/A2 work on Toxoplasma gondii (T gondii) is unknown. In this study, we found that the viability of tachyzoites that received HPRP-A1/A2 treatment was significantly decreased, and there was a reduction in the adhesion to and invasion of macrophages by tachyzoites after HPRP-A1/A2 treatment. HPRP-A1/A2 damaged the integrity of tachyzoite membranes, as characterized by membrane disorganization in and cytoplasm outflow from tachyzoites. In addition, in vivo injection with HPRP-A1/A2 resulted in a significantly decreased number of tachyzoites and an accelerated Th1/Tc1 response, and elicited pro-inflammatory cytokines in T gondii-infected mice. Furthermore, HPRP-A1/A2-treated splenocytes exhibited a significantly increased Tc1/Th1 response, and HPRP-A1/A2-stimulated macrophages inhibited the growth of carboxyfluorescein succinimidyl amino ester (CFSE)-labelled tachyzoites, which had higher TNF-α/IL-12 mRNA levels. Altogether, these results imply that HPRP-A1/A2 are effective against T gondii through damaging the structure of tachyzoites and inducing a protective immune response, which could offer an alternative approach against T gondii infection.