Plasmodium berghei PIMMS2 Promotes Ookinete Invasion of the Anopheles gambiae Mosquito Midgut

Ukegbu, Chiamaka V.; Akinosoglou, Karolina A.; Christophides, George K.; Vlachou, Dina

doi:10.1128/iai.00139-17

Cited by 15 publications

(23 citation statements)

References 55 publications

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“…SOPT exhibits subtilisin‐like structural features, however one or more catalytic residues are absent among many Plasmodium orthologs. While PbSOPT/PIMMS2 does possess the canonical catalytic triad, mutagenesis of the conserved Asp‐His‐Ser residues did not result in a loss‐of‐function phenotype as severe as that seen in knockout parasites (Ukegbu et al, ). Taken together, this indicates that the catalytic triad is not critical to the function of SOPT/PIMMS2 and suggest that it has a non‐enzymatic role in Plasmodium ookinete entry into the mosquito midgut epithelium, which is the first step of the traversal process.…”

Section: Discussionmentioning

confidence: 87%

“…stephensi midgut, consistent with a recent report that PIMMS2 is involved in midgut traversal in An. gambiae (Ukegbu et al, ). The similar loss‐of‐function phenotypes we observed using both P. falciparum and P. berghei mutants demonstrates that SOPT/PIMMS2 plays a conserved function in these two species during An.…”

Section: Resultsmentioning

confidence: 99%

“…Collectively, both this study and that of Ukegbu et al, () come to a similar conclusion that SOPT and PIMMS2 are involved in ookinete invasion of the mosquito midgut epithelium. While also apparently expressed/transcribed in merozoites and sporozoites (Florens et al, ; Lopez‐Barragan et al, ; Bunnik et al, ), genetic disruption of SOPT/PIMMS2 had no effect on asexual growth, gametocytogenesis, sporozoite infectivity or establishment of patent infections (Ukegbu et al, and this study).…”

Section: Discussionmentioning

confidence: 99%

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Plasmodium falciparum subtilisin‐like ookinete protein SOPT plays an important and conserved role during ookinete infection of the Anopheles stephensi midgut

Armistead

Jennison

O'Neill

et al. 2018

Molecular Microbiology

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Transmission of the malaria parasite Plasmodium falciparum involves infection of Anopheles mosquitoes. Here we characterize SOPT, a protein expressed in P. falciparum ookinetes that facilitates infection of the mosquito midgut. SOPT was identified on the basis that it contains a signal peptide, a PEXEL-like sequence and is expressed in asexual, ookinete and sporozoite stages, suggesting it is involved in infecting the human or mosquito host. SOPT is predicted to contain a subtilisin-like fold with a non-canonical catalytic triad and is orthologous to P. berghei PIMMS2. Localization studies reveal that SOPT is not exported to the erythrocyte but is expressed in ookinetes at the parasite periphery. SOPT-deficient parasites develop normally through the asexual and sexual stages and produce equivalent numbers of ookinetes to NF54 controls, however, they form fewer oocysts and sporozoites in mosquitoes. SOPT-deficient parasites were also unable to activate the immune-responsive midgut invasion marker SRPN6 after mosquito ingestion, suggesting they are defective for entry into the midgut. Disruption of SOPT in P. berghei (PIMMS2) did not affect other lifecycle stages or ookinete development but again resulted in fewer oocysts and sporozoites in mosquitoes. Collectively, this study shows that SOPT/PIMMS2 plays a conserved role in ookinetes of different Plasmodium species.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasmodium falciparum subtilisin‐like ookinete protein SOPT plays an important and conserved role during ookinete infection of the Anopheles stephensi midgut

Armistead

Jennison

O'Neill

et al. 2018

Molecular Microbiology

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“…A closer look at the genes found in cluster 7 from P. berghei revealed that it contains genes that are essential for the infectivity and maturation of ookinetes (Figure 3B). Specifically, a group of genes relating to the inner membrane complex, surface ookinete protein and secreted ookinete protein is required for efficient gliding motility and midgut traversal [ PBANKA_1354600 (ISC1), PBANKA_1025700 (IMC1l), PBANKA_0513000 (IMC1m) (36), PBANKA_1106900 (PIMMS2) (37), PBANKA_0714300 (HSP20) (38) and PBANKA_1432300 (CeITOS) (39)]. Another group of co-expressed genes contains perforins and a secreted protein, which are known to be important in midgut invasion where the parasite disrupts the membrane of the endothelial cell [ PBANKA_0824200 (PLP3), PBANKA_0711400 (PLP4), PBANKA_0711600 (PLP5) (40) and PBANKA_1037800 (SOAP) (41)].…”

Section: Resultsmentioning

confidence: 99%

www.Malaria.tools - comparative genomic and transcriptomic database for Plasmodium species

Tan

Mutwil

2019

Preprint

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10Malaria is a tropical parasitic disease caused by the Plasmodium genus, which resulted in an estimated 11 219 million cases of malaria and 435,000 malaria-related deaths in 2017. Despite the availability of the P. 12 falciparum genome since 2002, almost 50% of the genes remain unannotated. To remedy this paucity of 13 functional information, we used transcriptomic data to build gene co-expression networks for two 14 Plasmodium species (P. falciparum and P. berghei), and included genomic data of four other Plasmodium 15 species, P. yoleii, P. knowlesi, P. vivax and P. cynomolgi, as well as two non-Plasmodium species from 16 the Apicomplexa, Toxoplasma gondii and Theileria parva. The database is preloaded with tools that allow 17 the identification and cross-species comparison of co-expressed gene neighborhoods, clusters, and life 18 stage-specific expression, thus providing sophisticated tools to predict gene function. Moreover, we 19 exemplify how the tools can be used to easily identify genes relevant for pathogenicity and various life 20 stages of the malaria parasite. The database is freely available at https://malaria.tools. 21 22 Orthogroups D Kinesin-8, putative Radial spoke protein 3 Kinesin, putative GAS8-like protein Dynein light chain, putative Kinesin-like protein, putative MORN repeat Dynein light chain, putative Kinesin-8, putative Kinesin-like protein, putative Kinesin, putative

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“…These genes were given a candidate gene number preceded by the acronym PIMMS, for "Plasmodium Infection of the Mosquito Midgut Screen." We previously characterized PIMMS2 that encodes a subtilisin-like protein involved in midgut traversal (19). Here, we report the characterization of P. falciparum and P. berghei PIMMS43 that encodes a membrane-bound protein found on the surface of ookinetes and sporozoites.…”

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confidence: 98%

PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector

Ukegbu

Giorgalli

Tapanelli

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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After being ingested by a female Anopheles mosquito during a bloodmeal on an infected host, and before they can reach the mosquito salivary glands to be transmitted to a new host, Plasmodium parasites must establish an infection of the mosquito midgut in the form of oocysts. To achieve this, they must first survive a series of robust innate immune responses that take place prior to, during, and immediately after ookinete traversal of the midgut epithelium. Understanding how parasites may evade these responses could highlight new ways to block malaria transmission. We show that an ookinete and sporozoite surface protein designated as PIMMS43 (Plasmodium Infection of the Mosquito Midgut Screen 43) is required for parasite evasion of the Anopheles coluzzii complement-like response. Disruption of PIMMS43 in the rodent malaria parasite Plasmodium berghei triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing components of the complement-like system through RNAi largely restores ookinete-to-oocyst transition but oocysts remain small in size and produce a very small number of sporozoites that additionally are not infectious, indicating that PIMMS43 is also essential for sporogonic development in the oocyst. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African Plasmodium falciparum populations indicates allelic adaptation to sympatric vector populations. These data add to our understanding of mosquito–parasite interactions and identify PIMMS43 as a target of malaria transmission blocking.

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Plasmodium berghei PIMMS2 Promotes Ookinete Invasion of the Anopheles gambiae Mosquito Midgut

Cited by 15 publications

References 55 publications

Plasmodium falciparum subtilisin‐like ookinete protein SOPT plays an important and conserved role during ookinete infection of the Anopheles stephensi midgut

Plasmodium falciparum subtilisin‐like ookinete protein SOPT plays an important and conserved role during ookinete infection of the Anopheles stephensi midgut

www.Malaria.tools - comparative genomic and transcriptomic database for Plasmodium species

PIMMS43 is required for malaria parasite immune evasion and sporogonic development in the mosquito vector

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