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Updated: Jul 29, 2025
High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Integration of transcriptomics, proteomics, and metabolomics data for the detection of the human pathogenic
Jian Guo1, Juan Chen2, Teng Li1
1Department of Laboratory Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Abstract:
Prototheca species are the only microalgae known to cause opportunistic infections in vertebrates and humans. Most cases of protothecosis in humans are caused by Prototheca wickerhamii, but knowledge of the pathogenicity and biology of Prototheca is limited. Globally, the diagnostic rate of Prototheca species infection is much lower than the actual rate of P. wickerhamii. The precise mechanisms underlying the pathogenesis of Prototheca infections remain unclear. In this study, we identified a strain of P. wickerhamii with atypical colony morphology. To reveal the morphological differences between P. wickerhamii S1 (mucous) and the molecular basis of its pathogenicity, the transcriptomics, proteomics, and metabolomics of two pathogenic P. wickerhamii strains and one environmental strain were analysed. Interestingly, mannan endo-1,4-β-mannosidase was significantly downregulated in P. wickerhamii S1, which contributes to a thinner cell wall in S1 compared to strains with typical colony morphology, and the toxicity of macrophages is reduced. Metabolite analysis revealed that the mucoid appearance of P. wickerhamii S1 may have been caused by an increase in linoleic acid, glycerol, and other metabolites. There is still a need to better understand the ecology, aetiology, and pathogenesis of P. wickerhamii, and in particular, its transmission between humans, animals, and the environment, from a One Health perspective.
Insights
This study reveals molecular differences in Prototheca wickerhamii, identifying a strain with a thinner cell wall and reduced macrophage toxicity due to downregulated mannan endo-1,4-β-mannosidase. Increased linoleic acid and glycerol may cause its mucoid appearance.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis Studies
Background:
- Prototheca species are unique microalgae causing opportunistic infections in humans and vertebrates.
- Prototheca wickerhamii is the primary cause of human protothecosis, yet its pathogenicity and biology are poorly understood.
- The true incidence of Prototheca infections is likely underestimated globally.
Purpose of the Study:
- To investigate the morphological and molecular differences of an atypical mucous strain of Prototheca wickerhamii (S1).
- To elucidate the molecular basis of pathogenicity in Prototheca wickerhamii.
- To compare pathogenic and environmental strains of Prototheca wickerhamii.
Main Methods:
- Transcriptomics, proteomics, and metabolomics analyses were performed on two pathogenic and one environmental Prototheca wickerhamii strain.
- Comparative analysis focused on identifying differences between the mucous strain S1 and typical strains.
- Enzyme activity and metabolite levels were quantified.
Main Results:
- Mannan endo-1,4-β-mannosidase was significantly downregulated in the mucous strain S1.
- The S1 strain exhibited a thinner cell wall compared to typical strains, correlating with reduced macrophage toxicity.
- Increased levels of linoleic acid and glycerol were identified as potential contributors to the mucoid phenotype of S1.
Conclusions:
- Downregulation of mannan endo-1,4-β-mannosidase impacts cell wall integrity and pathogenicity in Prototheca wickerhamii.
- Metabolite profiles, including increased linoleic acid and glycerol, are associated with the mucoid morphology of P. wickerhamii S1.
- Further research is needed to understand the ecology, transmission, and pathogenesis of P. wickerhamii from a One Health perspective.
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