Impact of Protoporphyrin Lysine Derivatives on the Ability of Nosema ceranae Spores to Infect Honeybees

SIMPLE SUMMARY: Honeybees, which are important for the development and maintenance of natural ecosystems, are infected by microsporidia, Nosema apis and N. ceranae. These parasites induce a disease named nosemosis contributing to the impairment of digestion and nutrient absorption, ultimately leading to total colony collapse. The need for research into the control of N. ceranae has become increasingly important. Promising compounds for the treatment of nosemosis are porphyrins. In the present study, we examined the effects of three different porphyrins on the infectivity of N. ceranae microsporidia. A significantly lower level of infection was observed in the bees infected with the porphyrin-treated spores than in the control bees (infected with untreated spores). We showed that protoporphyrin lysine derivatives in particular prevented the development of Nosema spores and simultaneously extended bee life spans (up to 50%). The results also indicate that these porphyrins may contribute to the reduction in digestive nutrient absorption disorders in bees. The present findings can be used to develop a new class of drugs for combating nosemosis. These compounds may serve as preventive or disinfection agents through direct inactivation of Nosema both in the midgut and outside the host body, i.e., in the hive. ABSTRACT: The effect of two protoporphyrin IX derivatives conjugated with single (PP[Lys(TFA)-OH)](2)) or double (PP[Lys(TFA)-Lys(TFA)-OH](2)) lysine moieties on the infectious capacity of Nosema ceranae spores was examined, and their efficacies were compared with those of a cationic porphyrin (H(2)TTMePP). Honeybees were inoculated with spores preincubated with porphyrins or with untreated spores (control). A significantly lower level of infection was observed in the bees infected with the porphyrin-treated spores than in the infected control. Porphyrins 1 and 2 reduced the infectious capability of microsporidia more efficiently than porphyrin 3, with bee mortality declining to almost 50%. Confocal analysis of the midguts of infected bees revealed distinct differences in the number of spores between the control group and the group infected with PP[Lys(TFA)-Lys(TFA)-OH](2)-treated spores. Notably, bees with a reduced level of infection consumed less sucrose syrup than the control bees, indicating a reduction in digestive disorders and an improvement in food absorption.