Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants

ABSTRACT Malaria remains one of the most devastating parasitic diseases worldwide, with 90% of the malaria deaths in Africa in 2013 attributable to Plasmodium falciparum. The clinical symptoms of malaria include cycles of fever, corresponding to parasite rupture from red blood cells every 48 h. Para...

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Autores principales:	Phaedra Thomas, Jennifer Sedillo, Jenna Oberstaller, Suzanne Li, Min Zhang, Naresh Singh, Chengqi C. Q. Wang, Kenneth Udenze, Rays H. Y. Jiang, John H. Adams
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	forward genetics heat shock phenotype screen piggyBac transposon-mediated mutagenesis virulence factors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1a8eada6841d4355905b885d7c73688f
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spelling	oai:doaj.org-article:1a8eada6841d4355905b885d7c73688f2021-11-15T15:21:29ZPhenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants10.1128/mSphere.00273-162379-5042https://doaj.org/article/1a8eada6841d4355905b885d7c73688f2016-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00273-16https://doaj.org/toc/2379-5042ABSTRACT Malaria remains one of the most devastating parasitic diseases worldwide, with 90% of the malaria deaths in Africa in 2013 attributable to Plasmodium falciparum. The clinical symptoms of malaria include cycles of fever, corresponding to parasite rupture from red blood cells every 48 h. Parasite pathways involved in the parasite’s ability to survive the host fever response, and indeed, the functions of ~40% of P. falciparum genes as a whole, are still largely unknown. Here, we evaluated the potential of scalable forward-genetic screening methods to identify genes involved in the host fever response. We performed a phenotypic screen for genes linked to the parasite response to febrile temperatures by utilizing a selection of single-disruption P. falciparum mutants generated via random piggyBac transposon mutagenesis in a previous study. We identified several mutants presenting significant phenotypes in febrile response screens compared to the wild type, indicating possible roles for the disrupted genes in this process. We present these initial studies as proof that forward genetics can be used to gain insight into critical factors associated with parasite biology. IMPORTANCE Though the P. falciparum genome sequence has been available for many years, ~40% of its genes do not have informative annotations, as they show no detectable homology to those of studied organisms. More still have not been evaluated via genetic methods. Scalable forward-genetic approaches that allow interrogation of gene function without any pre-existing knowledge are needed to hasten understanding of parasite biology, which will expedite the identification of drug targets and the development of future interventions in the face of spreading resistance to existing frontline drugs. In this work, we describe a new approach to pursue forward-genetic phenotypic screens for P. falciparum to identify factors associated with virulence. Future large-scale phenotypic screens developed to probe other such interesting phenomena, when considered in parallel, will prove a powerful tool for functional annotation of the P. falciparum genome, where so much remains undiscovered.Phaedra ThomasJennifer SedilloJenna OberstallerSuzanne LiMin ZhangNaresh SinghChengqi C. Q. WangKenneth UdenzeRays H. Y. JiangJohn H. AdamsAmerican Society for Microbiologyarticleforward geneticsheat shockphenotype screenpiggyBactransposon-mediated mutagenesisvirulence factorsMicrobiologyQR1-502ENmSphere, Vol 1, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	forward genetics heat shock phenotype screen piggyBac transposon-mediated mutagenesis virulence factors Microbiology QR1-502
spellingShingle	forward genetics heat shock phenotype screen piggyBac transposon-mediated mutagenesis virulence factors Microbiology QR1-502 Phaedra Thomas Jennifer Sedillo Jenna Oberstaller Suzanne Li Min Zhang Naresh Singh Chengqi C. Q. Wang Kenneth Udenze Rays H. Y. Jiang John H. Adams Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
description	ABSTRACT Malaria remains one of the most devastating parasitic diseases worldwide, with 90% of the malaria deaths in Africa in 2013 attributable to Plasmodium falciparum. The clinical symptoms of malaria include cycles of fever, corresponding to parasite rupture from red blood cells every 48 h. Parasite pathways involved in the parasite’s ability to survive the host fever response, and indeed, the functions of ~40% of P. falciparum genes as a whole, are still largely unknown. Here, we evaluated the potential of scalable forward-genetic screening methods to identify genes involved in the host fever response. We performed a phenotypic screen for genes linked to the parasite response to febrile temperatures by utilizing a selection of single-disruption P. falciparum mutants generated via random piggyBac transposon mutagenesis in a previous study. We identified several mutants presenting significant phenotypes in febrile response screens compared to the wild type, indicating possible roles for the disrupted genes in this process. We present these initial studies as proof that forward genetics can be used to gain insight into critical factors associated with parasite biology. IMPORTANCE Though the P. falciparum genome sequence has been available for many years, ~40% of its genes do not have informative annotations, as they show no detectable homology to those of studied organisms. More still have not been evaluated via genetic methods. Scalable forward-genetic approaches that allow interrogation of gene function without any pre-existing knowledge are needed to hasten understanding of parasite biology, which will expedite the identification of drug targets and the development of future interventions in the face of spreading resistance to existing frontline drugs. In this work, we describe a new approach to pursue forward-genetic phenotypic screens for P. falciparum to identify factors associated with virulence. Future large-scale phenotypic screens developed to probe other such interesting phenomena, when considered in parallel, will prove a powerful tool for functional annotation of the P. falciparum genome, where so much remains undiscovered.
format	article
author	Phaedra Thomas Jennifer Sedillo Jenna Oberstaller Suzanne Li Min Zhang Naresh Singh Chengqi C. Q. Wang Kenneth Udenze Rays H. Y. Jiang John H. Adams
author_facet	Phaedra Thomas Jennifer Sedillo Jenna Oberstaller Suzanne Li Min Zhang Naresh Singh Chengqi C. Q. Wang Kenneth Udenze Rays H. Y. Jiang John H. Adams
author_sort	Phaedra Thomas
title	Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
title_short	Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
title_full	Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
title_fullStr	Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
title_full_unstemmed	Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants
title_sort	phenotypic screens identify parasite genetic factors associated with malarial fever response in <named-content content-type="genus-species">plasmodium falciparum</named-content><italic toggle="yes">piggybac</italic> mutants
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/1a8eada6841d4355905b885d7c73688f
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Phenotypic Screens Identify Parasite Genetic Factors Associated with Malarial Fever Response in <named-content content-type="genus-species">Plasmodium falciparum</named-content><italic toggle="yes">piggyBac</italic> Mutants

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