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Sword and shield: Linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense
Open accessAbstract
Group B Streptococcus(GBS) is a major cause of pneumonia, bacteremia, and meningitis in neonates and has been found to persist inside host phagocytic cells. The pore-forming GBS β-hemolysin/cytolysin (βH/C) encoded by cylE is an important virulence factor as demonstrated in several in vivo models. Interestingly,cylE deletion results not only in the loss of βH/C activity, but also in the loss of a carotenoid pigment of unknown function. In this study, we sought to define the mechanism(s) by which cylE may contribute to GBS phagocyte resistance and increased virulence potential. We found that cylE-deficient GBS was more readily cleared from a mouse's bloodstream, human whole blood, and isolated macrophage and neutrophil cultures. Survival was linked to the ability of βH/C to induce cytolysis and apoptosis of the phagocytes. At a lower bacterial inoculum,cylE also contributed to enhanced survival within phagocytes that was attributed to the ability of carotenoid to shield GBS from oxidative damage. In oxidant killing assays,cylE mutants were shown to be more susceptible to hydrogen peroxide, hypochlorite, superoxide, and singlet oxygen. Together, these data suggest a mechanism by which the linked cylE-encoded phenotypes, βH/C (sword) and carotenoid (shield), act in partnership to thwart the immune phagocytic defenses.
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Cites
Innate antimicrobial peptide protects the skin from invasive bacterial infection
Nizet, V., Ohtake, T., Lauth, X., Trowbridge, J., Rudisill, J., Dorschner, R. A., Pestonjamasp, V., Piraino, J., Huttner, K., & Gallo, R. L. (2001) · Nature · doi:10.1038/35106587 · Cited by 1,198
Self-citationDoran, K. S., Liu, G. Y., & Nizet, V. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17335 · Cited by 262
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Cited by
Liu, G. Y., Essex, A., Buchanan, J. T., Datta, V., Hoffman, H. M., Bastian, J. F., Fierer, J., & Nizet, V. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050846 · Cited by 752
Self-citationDoran, K. S., Engelson, E. J., Khosravi, A., Maisey, H. C., Fedtke, I., Equils, O., Michelsen, K. S., Arditi, M., Peschel, A., & Nizet, V. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23829 · Cited by 231
Self-citationMolecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy
Doran, K. S., & Nizet, V. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04266.x · Cited by 219
Self-citationHost–pathogen interactions in bacterial meningitis.
Doran, K. S., Fulde, M., Gratz, N., Kim, B. J., Nau, R., Prasadarao, N., Schubert-Unkmeir, A., Tuomanen, E. I., & Valentin-Weigand, P. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1531-z · Cited by 208
Self-citationAdult zebrafish model of bacterial meningitis in Streptococcus agalactiae infection
Patterson, H., Saralahti, A., Parikka, M., Dramsi, S., Trieu-Cuot, P., Poyart, C., Rounioja, S., & Rämet, M. (2012) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2012.07.007 · Cited by 83
Metadata
- Authors
- Liu, G. Y., Doran, K. S., Lawrence, T., Turkson, N., Puliti, M., Tissi, L., & Nizet, V.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-09-20
- Volume
- 101
- Issue
- 40
- Pages
- 14491-14496
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2149757052
- Cited by
- 229
- References
- 2
- FWCI
- 10.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Liu, G. Y., Doran, K. S., Lawrence, T., Turkson, N., Puliti, M., Tissi, L., & Nizet, V. (2004). Sword and shield: Linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0406143101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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