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ToolsSullivan, Matthew J., Goh, Kelvin G. K., Thapa, Ruby, Chattopadhyay, Debasish, Ipe, Deepak S., Duell, Benjamin L., Katupitiya, Lahiru, Gosling, Dean, Acharya, Dhruba and Ulett, Glen C. (2021) 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. Virulence, 12 (1). pp. 3015-3027. ISSN 2150-5594
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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 mutant that over-expresses GAPDH (oeGAPDH) from gapC using a constitutively active promoter, and analyzed 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, tumor 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. One-sentence summary: This study shows Streptococcus agalactiae glyceraldehyde 3-phosphate dehydrogenase, an enzyme that functions in glycolysis, gluconeogenesis and virulence, modifies phagocytosis outcomes, including cytokine synthesis, and affects bacterial persistence in the female reproductive tract.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by the National Health and Medical Research Council, Australia (Project Grants APP1146820 and APP1146569) (GCU). |
| Uncontrolled Keywords: | cytokine,glyceraldehyde-3-phosphate dehydrogenase,host-microbe interaction,innate immune response,pathogenesis,streptococcus agalactiae,parasitology,microbiology,immunology,microbiology (medical),infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2405 |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 15 Aug 2022 11:30 |
| Last Modified: | 06 Feb 2025 10:47 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/87251 |
| DOI: | 10.1080/21505594.2021.1989252 |
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