Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites.
BACKGROUND:In Plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. Further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. METHODOLOGY/PRINCIPAL FINDINGS:Reverse genetics was...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3528682?pdf=render |
_version_ | 1828748983639474176 |
---|---|
author | Godfree Mlambo Isabelle Coppens Nirbhay Kumar |
author_facet | Godfree Mlambo Isabelle Coppens Nirbhay Kumar |
author_sort | Godfree Mlambo |
collection | DOAJ |
description | BACKGROUND:In Plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. Further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. METHODOLOGY/PRINCIPAL FINDINGS:Reverse genetics was employed to examine the role of the meiotic specific recombinase Dmc1, a bacterial RecA homolog during sporogony in Plasmodium berghei. PbDmc1 knockout (KO) parasites showed normal asexual growth kinetics compared to WT parasites; however oocyst formation in mosquitoes was reduced by 50 to 80%. Moreover, the majority of oocysts were retarded in their growth and were smaller in size compared to WT parasites. Only a few Dmc1 KO parasites completed maturation resulting in formation of fewer sporozoites which were incapable of infecting naive mice or hepatocytes in vitro. PbDmc1 KO parasites were shown to be approximately 18 times more sensitive to Bizelesin, a DNA alkylating drug compared to WT parasites as reflected by impairment of oocyst formation and sporogonic development in the mosquito vector. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that PbDmc1 plays a critical role in malaria transmission biology. |
first_indexed | 2024-12-10T11:44:51Z |
format | Article |
id | doaj.art-d15ba1dd8d70448a99019bf6b72178b6 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-10T11:44:51Z |
publishDate | 2012-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-d15ba1dd8d70448a99019bf6b72178b62022-12-22T01:50:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5248010.1371/journal.pone.0052480Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites.Godfree MlamboIsabelle CoppensNirbhay KumarBACKGROUND:In Plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. Further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites. METHODOLOGY/PRINCIPAL FINDINGS:Reverse genetics was employed to examine the role of the meiotic specific recombinase Dmc1, a bacterial RecA homolog during sporogony in Plasmodium berghei. PbDmc1 knockout (KO) parasites showed normal asexual growth kinetics compared to WT parasites; however oocyst formation in mosquitoes was reduced by 50 to 80%. Moreover, the majority of oocysts were retarded in their growth and were smaller in size compared to WT parasites. Only a few Dmc1 KO parasites completed maturation resulting in formation of fewer sporozoites which were incapable of infecting naive mice or hepatocytes in vitro. PbDmc1 KO parasites were shown to be approximately 18 times more sensitive to Bizelesin, a DNA alkylating drug compared to WT parasites as reflected by impairment of oocyst formation and sporogonic development in the mosquito vector. CONCLUSIONS/SIGNIFICANCE:Our findings suggest that PbDmc1 plays a critical role in malaria transmission biology.http://europepmc.org/articles/PMC3528682?pdf=render |
spellingShingle | Godfree Mlambo Isabelle Coppens Nirbhay Kumar Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. PLoS ONE |
title | Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. |
title_full | Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. |
title_fullStr | Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. |
title_full_unstemmed | Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. |
title_short | Aberrant sporogonic development of Dmc1 (a meiotic recombinase) deficient Plasmodium berghei parasites. |
title_sort | aberrant sporogonic development of dmc1 a meiotic recombinase deficient plasmodium berghei parasites |
url | http://europepmc.org/articles/PMC3528682?pdf=render |
work_keys_str_mv | AT godfreemlambo aberrantsporogonicdevelopmentofdmc1ameioticrecombinasedeficientplasmodiumbergheiparasites AT isabellecoppens aberrantsporogonicdevelopmentofdmc1ameioticrecombinasedeficientplasmodiumbergheiparasites AT nirbhaykumar aberrantsporogonicdevelopmentofdmc1ameioticrecombinasedeficientplasmodiumbergheiparasites |