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Poly- N -Acetylglucosamine Production in Staphylococcus aureus Is Essential for Virulence in Murine Models of Systemic Infection
Open accessAbstract
The contribution of the Staphylococcus aureus surface polysaccharide poly- N -acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin ( ica ) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA -deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.
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Cites
Iron-Source Preference of Staphylococcus aureus Infections
Skaar, E. P., Humayun, M., Bae, T., DeBord, K. L., & Schneewind, O. (2004) · Science · doi:10.1126/science.1099930 · Cited by 440
Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1
Gómez, M. I., Lee, A., Reddy, B., Muir, A., Soong, G., Pitt, A., Cheung, A., & Prince, A. (2004) · Nature Medicine · doi:10.1038/nm1079 · Cited by 412
Mazmanian, S. K., Ton-That, H., Su, K., & Schneewind, O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032523999 · Cited by 372 · cited 1×
“Among these factors are bacterial proteins that bind to host extracellular matrix proteins that are referred to as MSCRAMMs (16, 65, 75); capsular polysaccharides (CP) such as CP5 and CP8 (54); extracellular toxins, hemolysins, and superantigens (36, 53, 62); protein A (20); mediators of antibiotic resistance (26, 67)…”
BackgroundKaplan, J. B., Velliyagounder, K., Ragunath, C., Rohde, H., Mack, D., Knobloch, J. K.-M., & Ramasubbu, N. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.24.8213-8220.2004 · Cited by 301
Cited by
Izano, E. A., Amarante, M. A., Kher, W. B., & Kaplan, J. B. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.02073-07 · Cited by 553
Molecular Basis of In Vivo Biofilm Formation by Bacterial Pathogens
Joo, H.-S., & Otto, M. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.10.022 · Cited by 434
A play in four acts: Staphylococcus aureus abscess formation
Cheng, A. G., DeDent, A. C., Schneewind, O., & Missiakas, D. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.01.007 · Cited by 310
Therapeutic Potential of Biofilm-Dispersing Enzymes
Kaplan, J. B. (2009) · The International Journal of Artificial Organs · doi:10.1177/039139880903200903 · Cited by 217
Detachment and Killing of Aggregatibacter actinomycetemcomitans Biofilms by Dispersin B and SDS
Izano, E. A., Wang, H., Ragunath, C., Ramasubbu, N., & Kaplan, J. B. (2007) · Journal of Dental Research · doi:10.1177/154405910708600707 · Cited by 123
Metadata
- Authors
- Kropec, A., Maira-Litran, T., Jefferson, K. K., Grout, M., Cramton, S. E., Götz, F., Goldmann, D. A., & Pier, G. B.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2005-10
- Volume
- 73
- Issue
- 10
- Pages
- 6868-6876
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- OpenAlex
- W2104283571
- Cited by
- 162
- References
- 4
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Kropec, A., Maira-Litran, T., Jefferson, K. K., Grout, M., Cramton, S. E., Götz, F., Goldmann, D. A., & Pier, G. B. (2005). Poly- N -Acetylglucosamine Production in Staphylococcus aureus Is Essential for Virulence in Murine Models of Systemic Infection. Infection and Immunity. https://doi.org/10.1128/iai.73.10.6868-6876.2005
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
