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J. Biol. Chem., Vol. 279, Issue 52, 54881-54886, December 24, 2004

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

Cuong Vuong, Stanislava Kocianova, Jovanka M. Voyich, Yufeng Yao, Elizabeth R. Fischer, Frank R. DeLeo, and Michael Otto

From the Laboratory of Human Bacterial Pathogenesis and Microscopy Core Facility, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840

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.

Received for publication, October 5, 2004 , and in revised form, October 21, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, NIAID, The National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840. Tel.: 406-363-9283; Fax: 406-375-9677; E-mail: motto{at}niaid.nih.gov.

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