Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite
Cerebral malaria caused by Plasmodium falciparum is the severest form of the disease resulting in the morbidity of a huge number of people worldwide. Development of effective curatives is essential in order to overcome the fatality of cerebral malaria. Earlier studies have shown the presence of sali...
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The Company of Biologists
2020-12-01
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| Online Access: | http://bio.biologists.org/content/9/12/bio054544 |
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| author | Malabika Chakrabarti Deepika Kannan Akshay Munjal Hadi Hasan Choudhary Satish Mishra Shailja Singh |
| author_facet | Malabika Chakrabarti Deepika Kannan Akshay Munjal Hadi Hasan Choudhary Satish Mishra Shailja Singh |
| author_sort | Malabika Chakrabarti |
| collection | DOAJ |
| description | Cerebral malaria caused by Plasmodium falciparum is the severest form of the disease resulting in the morbidity of a huge number of people worldwide. Development of effective curatives is essential in order to overcome the fatality of cerebral malaria. Earlier studies have shown the presence of salicylic acid (SA) in malaria parasite P. falciparum, which plays a critical role in the manifestation of cerebral malaria. Further, the application of SA for the treatment of acute symptoms in cerebral malaria increases the activity of iNOS leading to severe inflammation-mediated death, also called as Reye's syndrome. Therefore, modulation of the level of SA might be a novel approach to neutralize the symptoms of cerebral malaria. The probable source of parasite SA is the shikimate pathway, which produces chorismate, a precursor to aromatic amino acids and other secondary metabolites like SA in the parasite. In this work, we performed the immunological, pathological and biochemical studies in mice infected with chorismate synthase knocked-out Plasmodium berghei ANKA, which does not produce SA. Fewer cerebral outcomes were observed as compared to the mice infected with wild-type parasite. The possible mechanism behind this protective effect might be the hindrance of SA-mediated induction of autophagy in the parasite, which helps in its survival in the stressed condition of brain microvasculature during cerebral malaria. The absence of SA leading to reduced parasite load along with the reduced pathological symptoms contributes to less fatality outcome by cerebral malaria. |
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| language | English |
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| publishDate | 2020-12-01 |
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| spelling | doaj.art-9b4b79a800c2475d8ddc0b122fbd09a32022-12-21T22:02:15ZengThe Company of BiologistsBiology Open2046-63902020-12-0191210.1242/bio.054544054544Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasiteMalabika Chakrabarti0Deepika Kannan1Akshay Munjal2Hadi Hasan Choudhary3Satish Mishra4Shailja Singh5 Host-Parasite Interaction & Disease Modelling Laboratory, Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067, India Department of Life Science, Shiv Nadar University, Noida, UP 201314, India Host-Parasite Interaction & Disease Modelling Laboratory, Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067, India Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India Host-Parasite Interaction & Disease Modelling Laboratory, Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi-110067, India Cerebral malaria caused by Plasmodium falciparum is the severest form of the disease resulting in the morbidity of a huge number of people worldwide. Development of effective curatives is essential in order to overcome the fatality of cerebral malaria. Earlier studies have shown the presence of salicylic acid (SA) in malaria parasite P. falciparum, which plays a critical role in the manifestation of cerebral malaria. Further, the application of SA for the treatment of acute symptoms in cerebral malaria increases the activity of iNOS leading to severe inflammation-mediated death, also called as Reye's syndrome. Therefore, modulation of the level of SA might be a novel approach to neutralize the symptoms of cerebral malaria. The probable source of parasite SA is the shikimate pathway, which produces chorismate, a precursor to aromatic amino acids and other secondary metabolites like SA in the parasite. In this work, we performed the immunological, pathological and biochemical studies in mice infected with chorismate synthase knocked-out Plasmodium berghei ANKA, which does not produce SA. Fewer cerebral outcomes were observed as compared to the mice infected with wild-type parasite. The possible mechanism behind this protective effect might be the hindrance of SA-mediated induction of autophagy in the parasite, which helps in its survival in the stressed condition of brain microvasculature during cerebral malaria. The absence of SA leading to reduced parasite load along with the reduced pathological symptoms contributes to less fatality outcome by cerebral malaria.http://bio.biologists.org/content/9/12/bio054544cerebral malariasalicylic acidchorismate synthaseplasmodium falciparumplasmodium berghei anka |
| spellingShingle | Malabika Chakrabarti Deepika Kannan Akshay Munjal Hadi Hasan Choudhary Satish Mishra Shailja Singh Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite Biology Open cerebral malaria salicylic acid chorismate synthase plasmodium falciparum plasmodium berghei anka |
| title | Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite |
| title_full | Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite |
| title_fullStr | Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite |
| title_full_unstemmed | Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite |
| title_short | Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite |
| title_sort | chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid dependent autophagy response in parasite |
| topic | cerebral malaria salicylic acid chorismate synthase plasmodium falciparum plasmodium berghei anka |
| url | http://bio.biologists.org/content/9/12/bio054544 |
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