PMID- 25092910
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 82
IP  - 10
DP  - 2014 Oct
TI  - A conserved apicomplexan microneme protein contributes to Toxoplasma gondii 
      invasion and virulence.
PG  - 4358-68
LID - 10.1128/IAI.01877-14 [doi]
AB  - The obligate intracellular parasite Toxoplasma gondii critically relies on host 
      cell invasion during infection. Proteins secreted from the apical micronemes are 
      central components for host cell recognition, invasion, egress, and virulence. 
      Although previous work established that the sporozoite protein with an altered 
      thrombospondin repeat (SPATR) is a micronemal protein conserved in other 
      apicomplexan parasites, including Plasmodium, Neospora, and Eimeria, no genetic 
      evidence of its contribution to invasion has been reported. SPATR contains a 
      predicted epidermal growth factor domain and two thrombospondin type 1 repeats, 
      implying a role in host cell recognition. In this study, we assess the 
      contribution of T. gondii SPATR (TgSPATR) to T. gondii invasion by genetically 
      ablating it and restoring its expression by genetic complementation. Deltaspatr 
      parasites were ~50% reduced in invasion compared to parental strains, a defect 
      that was reversed in the complemented strain. In mouse virulence assays, Deltaspatr 
      parasites were significantly attenuated, with ~20% of mice surviving infection. 
      Given the conservation of this protein among the Apicomplexa, we assessed whether 
      the Plasmodium falciparum SPATR ortholog (PfSPATR) could complement the absence 
      of the TgSPATR. Although PfSPATR showed correct micronemal localization, it did 
      not reverse the invasion deficiency of Deltaspatr parasites, because of an apparent 
      failure in secretion. Overall, the results suggest that TgSPATR contributes to 
      invasion and virulence, findings that have implications for the many genera and 
      life stages of apicomplexans that express SPATR.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Huynh, My-Hang
AU  - Huynh MH
AD  - Department of Microbiology and Immunology, University of Michigan School of 
      Medicine, Ann Arbor, Michigan, USA.
FAU - Boulanger, Martin J
AU  - Boulanger MJ
AD  - Department of Biochemistry & Microbiology, University of Victoria, Victoria, 
      British Columbia, Canada.
FAU - Carruthers, Vern B
AU  - Carruthers VB
AD  - Department of Microbiology and Immunology, University of Michigan School of 
      Medicine, Ann Arbor, Michigan, USA vcarruth@umich.edu.
LA  - eng
GR  - R01 AI046675/AI/NIAID NIH HHS/United States
GR  - R03 AI060838/AI/NIAID NIH HHS/United States
GR  - MOP82915/CAPMC/CIHR/Canada
GR  - R01AI046675/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140804
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Protozoan Proteins)
RN  - 0 (Thrombospondins)
RN  - 0 (Virulence Factors)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Deletion
MH  - Genetic Complementation Test
MH  - Mice
MH  - Protozoan Proteins/genetics/*metabolism
MH  - Survival Analysis
MH  - Thrombospondins/genetics/*metabolism
MH  - Toxoplasma/genetics/*pathogenicity
MH  - Toxoplasmosis, Animal
MH  - Virulence
MH  - Virulence Factors/genetics/*metabolism
PMC - PMC4187870
EDAT- 2014/08/06 06:00
MHDA- 2014/11/13 06:00
PMCR- 2015/04/01
CRDT- 2014/08/06 06:00
PHST- 2014/08/06 06:00 [entrez]
PHST- 2014/08/06 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - IAI.01877-14 [pii]
AID - 01877-14 [pii]
AID - 10.1128/IAI.01877-14 [doi]
PST - ppublish
SO  - Infect Immun. 2014 Oct;82(10):4358-68. doi: 10.1128/IAI.01877-14. Epub 2014 Aug 
      4.