The mosquito-stage transcriptome of the neglected malaria parasite Plasmodium malariae reveals species-specific gene expression signatures and functional adaptations
6 affiliations
- 1Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain
- 2Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland
- 3Swiss Institute of Bioinformatics, Amphipôle, Quartier UNIL-Sorge, Lausanne, Switzerland
- 4MIVEGEC, IRD, CNRS, University of Montpellier, Montpellier, France
- 5Institut de Recherche en Sciences de la Santé (IRSS), Bobo Dioulasso, Burkina Faso
- 6Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
Abstract
Background: To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. This species remains enigmatic due to the inability to maintain it in long-term culture, the low parasitemia observed in human infections, and its frequent co-infection with other malaria species. Methodology/principal findings: We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis identified 3,699 expressed genes, of which 263 are developmentally regulated and 309 are P. malariae-specific, including genes with unknown functions and without orthologs in other Plasmodium spp. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. Several members of multigene families, such as PIR, PHIST, and fam-l, were found to be expressed, and new families potentially showing transcriptional heterogeneity were described. Conclusions/significance: Our findings indicate that the P. malariae transcriptome is largely conserved; however, a distinct set of expressed genes lacking detectable orthologs may contribute to differences in transmission and virulence. Given the scarcity of genomic and transcriptomic data for this pathogen and considering the global distribution of P. malariae and its potential role in sustaining malaria transmission, this study has direct implications for malaria control and elimination efforts. Author summary: Malaria is a globally significant disease caused by parasites of the genus Plasmodium. Of the six species known to infect humans, five are responsible for the vast majority of malaria cases worldwide. In this study, we investigate Plasmodium malariae, one of the least studied human malaria parasites. Research on this species has been limited because infections often go undetected owing to low parasite densities, and the inability to maintain the parasite in long-term culture has impeded detailed investigations of its biology and transmission. We investigated its transcriptome as the parasite develops inside the mosquito, a key stage for its transmission from one person to another. By analyzing gene activity at different time points during development, we identified which genes are turned on, many of which are unique to this species and still have no known function. We also identified genes that may act as key regulators of the process. Taken together, our results indicate that P. malariae has unique characteristics that distinguish it from other malaria parasites. Understanding these differences may help explain why it typically causes milder symptoms and provide useful information for improving disease control strategies.
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BibTeX
@article{ruiz2026mosquitostage,
title = {{The mosquito-stage transcriptome of the neglected malaria parasite Plasmodium malariae reveals species-specific gene expression signatures and functional adaptations}},
author = {José Luis Ruiz and Bárbara Díaz-Terenti and Thierry Lefèvre and Serge Rakiswendé Yerbanga Yerbanga and Thomas Dan Otto and Elena Gómez-Díaz},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = nov,
doi = {10.1371/journal.pntd.0014845},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014845},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The mosquito-stage transcriptome of the neglected malaria parasite Plasmodium malariae reveals species-specific gene expression signatures and functional adaptations
AU - José Luis Ruiz
AU - Bárbara Díaz-Terenti
AU - Thierry Lefèvre
AU - Serge Rakiswendé Yerbanga Yerbanga
AU - Thomas Dan Otto
AU - Elena Gómez-Díaz
PY - 2026
DA - 2026/11/02
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014845
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014845
AB - Background: To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. This species remains enigmatic due to the inability to maintain it in long-term culture, the low parasitemia observed in human infections, and its frequent co-infection with other malaria species. Methodology/principal findings: We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis identified 3,699 expressed genes, of which 263 are developmentally regulated and 309 are P. malariae-specific, including genes with unknown functions and without orthologs in other Plasmodium spp. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. Several members of multigene families, such as PIR, PHIST, and fam-l, were found to be expressed, and new families potentially showing transcriptional heterogeneity were described. Conclusions/significance: Our findings indicate that the P. malariae transcriptome is largely conserved; however, a distinct set of expressed genes lacking detectable orthologs may contribute to differences in transmission and virulence. Given the scarcity of genomic and transcriptomic data for this pathogen and considering the global distribution of P. malariae and its potential role in sustaining malaria transmission, this study has direct implications for malaria control and elimination efforts. Author summary: Malaria is a globally significant disease caused by parasites of the genus Plasmodium. Of the six species known to infect humans, five are responsible for the vast majority of malaria cases worldwide. In this study, we investigate Plasmodium malariae, one of the least studied human malaria parasites. Research on this species has been limited because infections often go undetected owing to low parasite densities, and the inability to maintain the parasite in long-term culture has impeded detailed investigations of its biology and transmission. We investigated its transcriptome as the parasite develops inside the mosquito, a key stage for its transmission from one person to another. By analyzing gene activity at different time points during development, we identified which genes are turned on, many of which are unique to this species and still have no known function. We also identified genes that may act as key regulators of the process. Taken together, our results indicate that P. malariae has unique characteristics that distinguish it from other malaria parasites. Understanding these differences may help explain why it typically causes milder symptoms and provide useful information for improving disease control strategies.
SN - 1935-2735
ER -