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

Summary 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.