Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification

Kolli, Surendra Kumar; Molina-Cruz, Alvaro; Araki, Toshiyuki; Geurten, Fiona J. A.; Ramesar, Jai; Chevalley-Maurel, Séverine; Kroeze, Hans; Bezemer, Sascha; Korne, Clarize M. de; Withers, Roxanne; Raytselis, Nadia; Hebieshy, Angela F. El; R, Kim; Child, Matthew A.; Kakuta, Soichiro; Hisaeda, Hajime; Kobayashi, Hirotaka; Annoura, Takeshi; Hensbergen, Paul J.; Franke-Fayard, Blandine; Barillas‐Mury, Carolina; Scheeren, Ferenc A.; Janse, Chris J.

doi:10.1073/pnas.2209729119

Cited by 15 publications

(14 citation statements)

References 70 publications

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“…Studies have shown that conformational changes or posttranslational modification (glutaminyl cyclase) of this surface protein prevents the melanization of oocysts and sporozoites of Plasmodium . 21 , 22 In the case of P. vivax , although it may evade the immunological response of An . darlingi , the vector’s ability to melanize free sporozoites in the hemocoel could be important in decreasing the transmission success of P. vivax .…”

Section: Discussionmentioning

confidence: 99%

Case Report: Plasmodium vivax Sporozoite Melanization in the Midgut and Salivary Gland of the Malaria Vector Anopheles darlingi

dos Santos,

Bastos,

Araújo

et al. 2024

The American Journal of Tropical Medicine and Hygiene

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Anopheles darlingi is the primary malaria vector in the Amazon region and is highly susceptible to both Plasmodium vivax and Plasmodium falciparum parasites. Although anopheline mosquitoes may develop melanotic encapsulation in response to Plasmodium parasites, there is no record of An. darlingi exhibiting a melanization response to P. vivax, the main malaria parasite in the Americas. Here, we report the occurrence of P. vivax sporozoite melanization in An. darlingi mosquitoes.

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Section: Discussionmentioning

confidence: 99%

Case Report: Plasmodium vivax Sporozoite Melanization in the Midgut and Salivary Gland of the Malaria Vector Anopheles darlingi

dos Santos,

Bastos,

Araújo

et al. 2024

The American Journal of Tropical Medicine and Hygiene

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“…The size and genetic complexity of Pf allows it during each infection to present thousands of elusive Ags, while in human host alone, the parasite changes the antigenic proteins at each life stage. In addition, the parasite has developed a series of strategies that allow it to confuse, hide, and misdirect the human immune system, [175] engendering additional difficulty in choosing vaccine Ag.…”

Section: 21mentioning

confidence: 99%

Innovative translational platforms for rapid developing clinical vaccines against COVID‐19 and other infectious disease

Wang,

Wang

2024

Biotechnology Journal

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A vaccine is a biological preparation that contains the antigen capable of stimulating the immune system to form the defense against pathogens. Vaccine development often confronts big challenges, including time/energy‐consuming, low efficacy, lag to pathogen emergence and mutation, and even safety concern. However, these seem now mostly conquerable through constructing the advanced translational platforms that can make innovative vaccines, sometimes, potentiated with a distinct multifunctional VADS (vaccine adjuvant delivery system), as evidenced by the development of various vaccines against the covid‐19 pandemic at warp speed. Particularly, several covid‐19 vaccines, such as the viral‐vectored vaccines, mRNA vaccines and DNA vaccines, regarded as the innovative ones that are rapidly made via the high technology‐based translational platforms. These products have manifested powerful efficacy while showing no unacceptable safety profile in clinics, allowing them to be approved for massive vaccination at also warp speed. Now, the proprietary translational platforms integrated with the state‐of‐the‐art biotechnologies, and even the artificial intelligence (AI), represent an efficient mode for rapid making innovative clinical vaccines against infections, thus increasingly attracting interests of vaccine research and development. Herein, the advanced translational platforms for making innovative vaccines, together with their design principles and immunostimulatory efficacies, are comprehensively elaborated.

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“…When the CSP’s glutaminyl cyclase target (glutamine) was subjected to mutation, a corresponding melanization of the sporozoites was observed. Hence the glutaminyl cyclase can be another druggable target (Kolli et al 2022 ). Several other proteins, such as TRAP, MSP, and others, have been reported to play critical roles in parasite evasions (Nakayama et al 2021 ).…”

Section: Malaria Parasite Survival Starts From the Mosquito Host — Ho...mentioning

confidence: 99%

Escaping the enemy’s bullets: an update on how malaria parasites evade host immune response

2023

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Malaria continues to cause untold hardship to inhabitants of malaria-endemic regions, causing significant morbidity and mortality that severely impact global health and the economy. Considering the complex life cycle of malaria parasites (MPs) and malaria biology, continued research efforts are ongoing to improve our understanding of the pathogenesis of the diseases. Female Anopheles mosquito injects MPs into its hosts during a blood meal, and MPs invade the host skin and the hepatocytes without causing any serious symptoms. Symptomatic infections occur only during the erythrocytic stage. In most cases, the host’s innate immunity (for malaria-naïve individuals) and adaptive immunity (for pre-exposed individuals) mount severe attacks and destroy most MPs. It is increasingly understood that MPs have developed several mechanisms to escape from the host’s immune destruction. This review presents recent knowledge on how the host’s immune system destroys invading MPs as well as MPs survival or host immune evasion mechanisms. On the invasion of host cells, MPs release molecules that bind to cell surface receptors to reprogram the host in a way to lose the capacity to destroy them. MPs also hide from the host immune cells by inducing the clustering of both infected and uninfected erythrocytes (rosettes), as well as inducing endothelial activation. We hope this review will inspire more research to provide a complete understanding of malaria biology and promote interventions to eradicate the notorious disease.

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Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification

Cited by 15 publications

References 70 publications

Case Report: Plasmodium vivax Sporozoite Melanization in the Midgut and Salivary Gland of the Malaria Vector Anopheles darlingi

Case Report: Plasmodium vivax Sporozoite Melanization in the Midgut and Salivary Gland of the Malaria Vector Anopheles darlingi

Innovative translational platforms for rapid developing clinical vaccines against COVID‐19 and other infectious disease

Escaping the enemy’s bullets: an update on how malaria parasites evade host immune response

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