A Crucial Role for Exopolysaccharide Modification in Bacterial Biofilm Formation, Immune Evasion, and Virulence*

By C. Vuong, Stanislava Kocianova, Jovanka M. Voyich, Yufeng Yao, E. Fischer, F. DeLeo, M. Otto. Journal of Biological Chemistry, 2004

607 citations recorded by the source corpus.

Biofilms play an important role in many chronic bacterial infections. Production of an extracellular mixture of sugar polymers called exopolysaccharide is characteristic and critical for biofilm formation. However, there is limited information about the mechanisms involved in the biosynthesis and modification of exopolysaccharide components and how these processes influence bacterial pathogenesis. Staphylococcus epidermidis is an important human pathogen that frequently causes persistent infections by biofilm formation on indwelling medical devices. It produces a poly-N-acetylglucosamine molecule that emerges as an exopolysaccharide component of many bacterial pathogens. Using a novel method based on size exclusion chromatography-mass spectrometry, we demonstrate that the surface-attached protein IcaB is responsible for deacetylation of the poly-N-acetylglucosamine molecule. Most likely due to the loss of its cationic character, non-deacetylated poly-acetylglucosamine in an isogenic icaB mutant strain was devoid of the ability to attach to the bacterial cell surface. Importantly, deacetylation of the polymer was essential for key virulence mechanisms of S. epidermidis, namely biofilm formation, colonization, and resistance to neutrophil phagocytosis and human antibacterial peptides. Furthermore, persistence of the icaB mutant strain was significantly impaired in a murine model of device-related infection. This is the first study to describe a mechanism of exopolysaccharide modification that is indispensable for the development of biofilm-associated human disease. Notably, this general virulence mechanism is likely similar for other pathogenic bacteria and constitutes an excellent target for therapeutic maneuvers aimed at combating biofilm-associated infection.

Subfields: Infectious Diseases, Molecular Biology, Periodontics

View Paper: https://www.semanticscholar.org/paper/0357954acc5e7df34cee5349483578d41a8a75cd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. M. Otto
2. R. Vasudevan
3. P. Watnick
4. E. Karatan
5. Christopher J Jones
6. D. Wozniak
7. D. Limoli
8. G. Peters

In Molecular Biology

1. M. Otto
2. R. Vasudevan
3. P. Watnick
4. E. Karatan
5. D. Wozniak
6. Christopher J Jones
7. D. Limoli
8. G. Peters

In Periodontics

1. M. Otto
2. Christopher J Jones
3. P. Watnick
4. D. Wozniak
5. R. Vasudevan
6. E. Karatan
7. D. Limoli

Citations in the corpus

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• Bacterial Extracellular Polysaccharides in Biofilm Formation and Function (2015, background): “…of PIA during staphylococci infections has been extensively studied, and several roles have been attributed to PIA, such as promoting cellular aggregation and bio fi lm formation, increased virulence, and protection from host innate immune responses (34 – 36; reviewed in references 25, 37 – 40).”
• Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues (2009, background): “PNAG (or PIA), a linear (1–6)-linked glucosaminoglycan, is composed of 2-deoxy-2-amino-dglucopyranosyl residues, of which 80–85% are N-acetylated (29); the remaining glucosamine residues are positively charged and promote association of the polysaccharide with the bacterial envelope (30).”
• ica and beyond: biofilm mechanisms and regulation in Staphylococcus epidermidis and Staphylococcus aureus. (2007, background): “The surface-attached protein IcaB is then responsible for deacetylation of the poly-N-acetylglucosamine molecule (Vuong et al., 2004).”
• Antimicrobial peptides: key components of the innate immune system (2012, methodology): “epidermidis, in addition to protease production, use other methods such as forming biofilms, changing hydrophobicity and permeability of outer membranes (Guo et al., 1998; Peschel, 2002; Vuong et al., 2004a; Vuong et al., 2004b; Otto, 2006) to protect themselves from the AMPs.”
• Staphylococcus epidermidis – the “accidental” pathogen (2009, background): “Partial de-acetylation of the GlcNAc residues is accomplished by the cell surface-located enzyme IcaB after expor”
• Coagulase-Negative Staphylococci (2014, background): “Furthermore, the partial deacetylation of PIA/ PNAG mediated by IcaB determined its biological activity in immune evasion, since it was essential for resistance to phagocytosis by PMNs and to human antimicrobial peptides (AMPs) (291).”
• Biofilms: Microbial Cities of Scientific Significance (2014, background): “Accumulation and intracellular aggregation: The crucial aspect involved in intercellular adhesion is polysaccharide intercellular adhesin (PIA), which is similar to poly-N-acetylglucosamine [33].”
• Staphylococcal biofilms (2018, methodology): “AMPs are also produced in the skin, where they are secreted to control skin-colonizing or -infecting bacteria (119).”
• Bacterial Extracellular Polysaccharides Involved in Biofilm Formation (2009, background): “aeruginosa are the most prevalent pathogens involved in clinical chronic infections [13,64].”
• Pathogenicity and virulence of Staphylococcus aureus (2021, background): “attracts the molecule to the negatively charged bacterial surface [84,85].”