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
| Autor: | Glen C. Ulett, Lahiru Katupitiya, Deepak S. Ipe, Dhruba Acharya, Matthew J. Sullivan, Debasish Chattopadhyay, Dean Gosling, Ruby Thapa, Benjamin L. Duell, Kelvin G. K. Goh |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
host-microbe interaction Phagocytosis medicine.medical_treatment Immunology Virulence Infectious and parasitic diseases RC109-216 medicine.disease_cause Microbiology Mice stomatognathic system medicine cytokine Animals Humans Immunologic Factors Macrophage inflammatory protein Glyceraldehyde 3-phosphate dehydrogenase glyceraldehyde-3-phosphate dehydrogenase Innate immune system biology pathogenesis Glyceraldehyde-3-Phosphate Dehydrogenases Infectious Diseases Cytokine Streptococcus agalactiae biology.protein innate immune response Cytokines Parasitology Tumor necrosis factor alpha Female streptococcus agalactiae Research Article Research Paper |
| Zdroj: | Virulence, Vol 12, Iss 1, Pp 3015-3027 (2021) Virulence article-version (VoR) Version of Record |
| DOI: | 10.6084/m9.figshare.16802467.v2 |
| Popis: | 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. 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 effects bacterial persistence in the female reproductive tract. |
| Databáze: | OpenAIRE |
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