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  • Streptococcus agalactiae glyceraldehyde-3-phosphate dehydrogenase (GAPDH) elicits multiple cytokines from human cells and has a minor effect on bacterial persistence in the murine female reproductive tract

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    Sullivan517097-Published.pdf (2.172Mb)
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    Version of Record (VoR)
    Author(s)
    Sullivan, Matthew J
    Goh, Kelvin GK
    Thapa, Ruby
    Chattopadhyay, Debasish
    Ipe, Deepak S
    Duell, Benjamin L
    Katupitiya, Lahiru
    Gosling, Dean
    Acharya, Dhruba
    Ulett, Glen C
    Griffith University Author(s)
    Thapa, Ruby
    Goh, Kelvin
    Sullivan, Matthew J.
    Ulett, Glen C.
    Ipe, Deepak S.
    Acharya, Dhruba
    Katupitiya, Lahiru
    Gosling, Dean A.
    Duell, Ben L.
    Year published
    2021
    Metadata
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    Abstract
    Streptococcus agalactiae glyceraldehyde 3-phosphate dehydrogenase (GAPDH), encoded by gapC, is a glycolytic enzyme that is associated with virulence and immune-mediated protection. However, the role of GAPDH in cellular cytokine responses to S. agalactiae, bacterial phagocytosis and colonization of the female reproductive tract, a central host niche, is unknown. We expressed and studied purified recombinant GAPDH (rGAPDH) of S. agalactiae in cytokine elicitation assays with human monocyte-derived macrophage, epithelial cell, and polymorphonuclear leukocyte (PMN) co-culture infection models. We also generated a S. agalactiae ...
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    Streptococcus agalactiae glyceraldehyde 3-phosphate dehydrogenase (GAPDH), encoded by gapC, is a glycolytic enzyme that is associated with virulence and immune-mediated protection. However, the role of GAPDH in cellular cytokine responses to S. agalactiae, bacterial phagocytosis and colonization of the female reproductive tract, a central host niche, is unknown. We expressed and studied purified recombinant GAPDH (rGAPDH) of S. agalactiae in cytokine elicitation assays with human monocyte-derived macrophage, epithelial cell, and polymorphonuclear leukocyte (PMN) co-culture infection models. We also generated a S. agalactiae mutant that over-expresses GAPDH (oeGAPDH) from gapC using a constitutively active promoter, and analysed the mutant in murine macrophage antibiotic protection assays and in virulence assays in vivo, using a colonization model that is based on experimental infection of the reproductive tract in female mice. Human cell co-cultures produced interleukin (IL)-1β, IL-6, macrophage inflammatory protein (MIP)-1, tumour necrosis factor (TNF)-α and IL-10 within 24 h of exposure to rGAPDH. PMNs were required for several of these cytokine responses. However, over-expression of GAPDH in S. agalactiae did not significantly affect measures of phagocytic uptake compared to an empty vector control. In contrast, oeGAPDH-S. agalactiae showed a small but statistically significant attenuation for persistence in the reproductive tract of female mice during the chronic phase of infection (10-28 days post-inoculation), relative to the vector control. We conclude that S. agalactiae GAPDH elicits production of multiple cytokines from human cells, and over-expression of GAPDH renders the bacterium more susceptible to host clearance in the female reproductive tract.
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    Journal Title
    Virulence
    DOI
    https://doi.org/10.1080/21505594.2021.1989252
    Copyright Statement
    © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Note
    This publication has been entered in Griffith Research Online as an advanced online version.
    Subject
    Medical microbiology
    Bacteriology
    Streptococcus agalactiae
    cytokine
    glyceraldehyde-3-phosphate dehydrogenase
    host-microbe interaction
    innate immune response
    Publication URI
    http://hdl.handle.net/10072/409153
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    • Journal articles

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