Insights into the L3 to L4 developmental program through proteomics Article Swipe
Sasisekhar Bennuru
,
Zhaojing Meng
,
James H. McKerrow
,
Sara Lustigman
,
Thomas B. Nutman
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.05.06.439182
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.05.06.439182
The establishment of infection with the lymphatic dwelling filarial parasites is dependent on the infectivity and subsequent development of the infective larvae (L3) within the human host to later stages (L4, adults) that require several developmental molts. The molecular mechanisms underlying the developmental processes in parasitic nematodes are not clearly defined. We report the proteomic profiles throughout the entire L3 to L4 molt using an established in vitro molting process for the human pathogen B. malayi . A total of 3466 proteins of B. malayi and 54 from Wolbachia were detected at one or more time points. Based on the proteomic profiling, the L3 to L4 molting proteome can be broadly divided into an early, middle and late phase. Enrichment of proteins, protein families and functional categories between each time point or between phases primarily relate to energy metabolism, immune evasion through secreted proteins, protein modification, and extracellular matrix-related processes involved in the development of new cuticle. Comparative analyses with somatic proteomes and transcriptomes highlighted the differential usage of cysteine proteinases (CPLs), BmCPL-1, -4 and -5 in the L3-L4 molt compared to the adults and microfilariae. Inhibition of the CPLs effectively blocked the in-vitro L3 to L4 molt. Overall, only 4 Wolbachia proteins (Wbm0495, Wbm0793, Wbm0635, and Wbm0786) were detected across all time points and suggest that they play an inconsequential role in the early developmental process. Importance The neglected tropical diseases of lymphatic filariasis, onchocerciasis (or river blindness), and loiasis are the three major filarial infections of humans that cause long-term disability, impaired childhood growth, reduced reproductive capacity. Global efforts to control and/or eliminate these infections as a public health concern are based on strategies and tools to strengthen the diagnostics, therapeutic and prophylactic measures. A deeper understanding of the genes, proteins and pathways critical for the development of the parasite is needed to help further investigate the mechanisms of parasite establishment and disease progression, because not all the transmitted infective larvae get to develop successfully and establish infections. The significance of this study is in identifying the proteins and the pathways that are needed by the parasite for successful developmental molts, that in turn will allow for investigating targets of therapeutic and prophylactic potential.
Related Topics
Concepts
Biology
Proteome
Wolbachia
Brugia malayi
Lymphatic filariasis
Proteomics
Onchocerciasis
Infectivity
Moulting
Developmental biology
Cell biology
Immunology
Filariasis
Larva
Bioinformatics
Genetics
Helminths
Ecology
Host (biology)
Gene
Virus
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.05.06.439182
- https://www.biorxiv.org/content/biorxiv/early/2021/05/06/2021.05.06.439182.full.pdf
- OA Status
- green
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3159622868
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3159622868Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.05.06.439182Digital Object Identifier
- Title
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Insights into the L3 to L4 developmental program through proteomicsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
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2021Year of publication
- Publication date
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2021-05-06Full publication date if available
- Authors
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Sasisekhar Bennuru, Zhaojing Meng, James H. McKerrow, Sara Lustigman, Thomas B. NutmanList of authors in order
- Landing page
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https://doi.org/10.1101/2021.05.06.439182Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/05/06/2021.05.06.439182.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/05/06/2021.05.06.439182.full.pdfDirect OA link when available
- Concepts
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Biology, Proteome, Wolbachia, Brugia malayi, Lymphatic filariasis, Proteomics, Onchocerciasis, Infectivity, Moulting, Developmental biology, Cell biology, Immunology, Filariasis, Larva, Bioinformatics, Genetics, Helminths, Ecology, Host (biology), Gene, VirusTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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65Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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