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Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261
* To whom correspondence should be addressed. Email:
shanksrm{at}upmc.edu.
The mechanisms by which environmental carbon sources regulate biofilm formation are poorly understood. This study investigates the role of glucose and the catabolite repression system in Serratia marcescens biofilm formation. The ability of this opportunistic pathogen to proliferate in a wide range of environments, to cause disease, and to resist antimicrobials is linked to its ability to form biofilms. We observed that growth of S. marcescens in glucose-rich medium strongly stimulated biofilm formation, which contrasts with previous studies showing that biofilm formation is inhibited by glucose in Escherichia coli and other enteric bacteria. Glucose uptake is known to inversely mediate intracellular cAMP synthesis through regulation of adenylate cyclase (cyaA) activity, which in turn controls fundamental processes such as motility, carbon utilization and storage, pathogenesis, and cell division in many bacteria. Here we demonstrate that mutation of catabolite repression genes that regulate cAMP levels (crr, cyaA) or the ability to respond to cAMP (crp), confer a large increase in biofilm formation. Suppressor analysis revealed that phenotypes of a cAMP receptor protein (crp) mutant require the fimABCD operon, which is responsible for type 1 fimbriae production. Consistently, fimA transcription and fimbriae production were determined to be upregulated in a cyaA mutant background using quantitative real-time RT-PCR and TEM analysis. The regulatory pathway by which environmental carbon sources influence cAMP concentrations to alter production of type 1 fimbrial adhesins establishes a novel mechanism by which bacteria control biofilm development.
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
The cAMP-dependent catabolite repression system of Serratia marcescens mediates biofilm formation through regulation of type 1 fimbriae
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