# High-resolution proteomics unveils salivary gland disruption and saliva-hemolymph protein exchange in Plasmodium-infected mosquitoes

**Authors:** Thiago Luiz Alves e Silva, Sachi Kanatani, Ana Beatriz Barletta Ferreira, Cindi L. Schwartz, Benjamin Liffner, Octavio A. C. Talyuli, Janet Olivas, Bianca M. Nagata, Zarna Rajeshkumar Pala, Tales Pascini, Derron A. Alves, Ming Zhao, Motoshi Suzuki, Lilian P. Dorner, Friedrich Frischknecht, Isabelle Coppens, Carolina Barillas-Mury, Sabrina Absalon, Jose M. C. Ribeiro, Photini Sinnis, Joel Vega-Rodriguez

PMC · DOI: 10.1038/s41467-025-64837-6 · Nature Communications · 2025-11-20

## TL;DR

This study shows how malaria parasites damage mosquito salivary glands and change saliva proteins, which could help the parasites spread better.

## Contribution

The study reveals how Plasmodium infection disrupts mosquito salivary glands and causes protein exchange between saliva and hemolymph.

## Key findings

- Plasmodium infection causes structural damage to mosquito salivary glands, allowing hemolymph proteins to enter.
- Saliva from infected mosquitoes shows reduced immune proteins, possibly due to sporozoite interactions.
- Saliva protein changes are similar across Plasmodium species, suggesting a conserved interaction mechanism.

## Abstract

Plasmodium sporozoites, the infective stage of malaria, must invade the mosquito salivary glands (SGs) before being transmitted to a vertebrate host. However, the physiological and biochemical effects of this invasion remain largely unexplored. We examined the impact of Plasmodium infection on Anopheles gambiae salivary glands using high-resolution proteomics, gene expression, and morphological analysis. The data reveal differential expression of various proteins, including the enrichment of hemolymph-derived humoral proteins in infected salivary glands. These proteins diffuse into the SGs due to structural damage caused by the sporozoites during invasion, while saliva proteins diffuse out into the circulation. Moreover, proteomic analysis of saliva from P. berghei– or P. falciparum–infected mosquitoes revealed changes in composition, with a pronounced reduction of immune proteins relative to uninfected mosquitoes. This reduction is likely due to the association of these proteins with the surface of sporozoites and/or changes in the saliva’s physical properties within the invaded salivary secretory cavities. The saliva protein profiles from mosquitoes infected with both Plasmodium species are remarkably similar, suggesting a conserved interaction between sporozoites and salivary glands. Our results provide a foundation for understanding the molecular interactions between Plasmodium sporozoites and mosquito salivary glands.

Plasmodium sporozoites must invade mosquito salivary glands to facilitate malaria transmission, yet the effects of this invasion are not well understood. Here, the authors use high-resolution proteomics and show that malaria parasite invasion damages mosquito salivary glands, alters saliva protein composition, and attracts immune cells, potentially increasing parasite transmission.

## Linked entities

- **Diseases:** malaria (MONDO:0005136)
- **Species:** Plasmodium (taxon 5820), Anopheles gambiae (taxon 7165)

## Full-text entities

- **Diseases:** Plasmodium infection (MESH:D008288)
- **Species:** Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Plasmodium berghei (species) [taxon 5821], Anopheles gambiae (African malaria mosquito, species) [taxon 7165]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12635079/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12635079/full.md

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Source: https://tomesphere.com/paper/PMC12635079