A Plasmodium falciparum ATP-binding cassette transporter is essential for liver stage entry into schizogony
Debashree Goswami,
Sudhir Kumar,
William Betz,
Janna M. Armstrong,
Meseret T. Haile,
Nelly Camargo,
Chaitra Parthiban,
Annette M. Seilie,
Sean C. Murphy,
Ashley M. Vaughan,
Stefan H.I. Kappe
Affiliations
Debashree Goswami
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
Sudhir Kumar
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
William Betz
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
Janna M. Armstrong
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
Meseret T. Haile
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
Nelly Camargo
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA
Chaitra Parthiban
Department of Laboratory Medicine and Pathology and Department of Microbiology, University of Washington, Seattle, WA, USA
Annette M. Seilie
Department of Laboratory Medicine and Pathology and Department of Microbiology, University of Washington, Seattle, WA, USA
Sean C. Murphy
Department of Laboratory Medicine and Pathology and Department of Microbiology, University of Washington, Seattle, WA, USA
Ashley M. Vaughan
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA
Stefan H.I. Kappe
Center for Global Infectious Disease Research, Seattle Children’s Research Institute, 307 Westlake Avenue N, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Corresponding author
Summary: Plasmodium sporozoites invade hepatocytes and transform into liver stages within a parasitophorous vacuole (PV). The parasites then grow and replicate their genome to form exoerythrocytic merozoites that infect red blood cells. We report that the human malaria parasite Plasmodium falciparum (Pf) expresses a C-type ATP-binding cassette transporter, Pf ABCC2, which marks the transition from invasive sporozoite to intrahepatocytic early liver stage. Using a humanized mouse infection model, we show that Pf ABCC2 localizes to the parasite plasma membrane in early and mid-liver stage parasites but is not detectable in late liver stages. Pf abcc2— sporozoites invade hepatocytes, form a PV, and transform into liver stage trophozoites but cannot transition to exoerythrocytic schizogony and fail to transition to blood stage infection. Thus, Pf ABCC2 is an expression marker for early phases of parasite liver infection and plays an essential role in the successful initiation of liver stage replication.
