Phosphoglycerate mutase 1 is implicated in maduramycin resistance and host cell invasion in Eimeria tenella.

Abstract

Avian coccidiosis, caused by apicomplexan parasites of the genus Eimeria, poses a major threat to the global poultry industry, with Eimeria tenella being a highly pathogenic species. The emergence of widespread drug resistance due to long-term anticoccidial use underscores the need to elucidate resistance mechanisms. This study focuses on phosphoglycerate mutase 1 (PGAM1), a key glycolytic enzyme implicated in drug resistance in other contexts like cancer. We cloned and characterized the EtPGAM1 gene from E. tenella, which encodes a 250-amino-acid protein that is relatively conserved among apicomplexans. Transcriptional analysis revealed significant upregulation of EtPGAM1 in a maduramycin-resistant strain and in field isolates exhibiting multi-drug resistance. Immunofluorescence localized EtPGAM1 to the cytoplasm and peripheral regions of sporozoites and merozoites. Importantly, an in vitro invasion inhibition assay demonstrated that anti-rEtPGAM1 antibody could concentration-dependently block sporozoite invasion of host cells.The elevated expression of EtPGAM1 under drug pressure indicates that it may be involved in the parasite's adaptive response to anticoccidial treatment. In conclusion, antibody targeting of EtPGAM1 inhibits sporozoite invasion in vitro, and offers a basis for further investigation into metabolic adaptation mechanisms associated with anticoccidial resistance.