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A single nucleotide polymorphism in an AP2 transcription factor encoded in the malaria-causing Plasmodium berghei alters the development of host immunity

Wednesday, September 13, 2017 — Poster Session II

3:30 p.m. – 5:00 p.m.
FAES Terrace
NIAID
MICROBIO-5

Authors

  • CK Cimperman
  • P Sheehan
  • M Akkaya
  • A Bansal
  • G Arora
  • A Molina-Cruz
  • CF Qi
  • M Pena

Abstract

The Apetela2 (AP2) family of transcription factors is a major regulator of Plasmodium parasite gene expression. Twenty-seven members of this family have been identified since their discovery in 2005. However, our understanding that AP2 members regulate key features of Plasmodium biology is incomplete. Here we describe the impact of a single nucleotide polymorphism (SNP) in the active site of the AP2 protein, PBANKA_011210, on the outcome of infection in mice. Plasmodium berghei Anka (PbA), the only rodent parasite that causes experimental cerebral malaria (ECM), codes for a phenylalanine at position 1823. All other Plasmodium parasite strains, none of which cause ECM in mice, including PbNK65, have a serine in this position. Using CRISPR, we modified the PbNK65 parasite (PbNK65-WT) to encode the PbA SNP (PbNK65-PbA). The course of infection with PbNK65-WT or PbNK65-PbA were similar and showed no ECM pathology indicating that the PbA AP2 SNP is not sufficient to cause ECM. However, mice infected with PbNK65-PbA generated dramatically higher germinal center responses and produced higher titers of parasite-specific antibodies. When infected mice were treated with sub-therapeutic doses of the anti-malarial, chloroquine, PbNK65-PbA-infected mice cleared the infection whereas PbNK65-WT-infected mice were unable to control the infection resulting in severe anemia and death. These results reveal a novel role of AP2 proteins in controlling host immunity to Plasmodium infections.

Category: Microbiology and Infectious Diseases