Bacterial biofilms are able to form on almost any surface. Because of the impact that biofilms have on diverse environments, from indwelling devices in hospital patients to water pipes, there has been a great interest in investigating the molecular mechanisms underlying biofilm formation and maintenance. As a consequence we now know a large amount regarding the molecular biology of the biofilms formed by numerous model bacteria. While different bacteria utilize different pathways to build a biofilm, a common feature emerges. An extracellular matrix - generally composed of polysaccharides, proteins, and nucleic acids - holds the biofilm-associated cells together. A full understanding of the processes that control matrix production is required if we are to develop better ways to control and manipulate bacterial biofilms. Over the past two decades our laboratory has focused on studying the process of biofilm formation by the Gram-positive model bacterium Bacillus subtilis. As a result we know possess a deep understanding of the regulatory circuitry that governs matrix production in this organism. The vast majority of our studies have been carried out using small variations on one set of laboratory conditions that were specifically designed to yield very robust biofilms. We are now in a position to take biofilm analyses to the next level. With our current understanding as a starting point, we will now expand our studies to many different environmental conditions. Importantly, we will determine how biofilm formation is influenced by other bacterial species and how it differs when it happen on the surface of a plant's roots. We propose to carry out systems-level analyses of the different responses that B. subtilis mounts during biofilm formation under such diverse condition. Such an approach has not been taken to study biofilms before. To address this gap in knowledge, we will focus our work along the follow four specific aims: 1) Development and Application of New Methodologies to Study B. subtilis Biofilms. 2) A Systems-Level Approach to Understanding Changes in Biofilm Physiology. 3) Interspecies Modulation of Biofilm Formation. 4) The Role of the Environment in Root Colonization and Biofilm Formation.

Public Health Relevance

Bacteria are remarkably adept at colonizing surfaces in a process known as biofilm formation. When biofilms form on the wrong surfaces, such as on open wounds or on implanted medical devices, they can cause chronic infections that are extremely difficult to eradicate. By studying the molecular details of how bacteria form biofilms under many different conditions and on diverse surfaces we can devise strategies to interfere with the process.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01GM058213-17
Application #
8785292
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sledjeski, Darren D
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Balbontín, Roberto; Vlamakis, Hera; Kolter, Roberto (2014) Mutualistic interaction between Salmonella enterica and Aspergillus niger and its effects on Zea mays colonization. Microb Biotechnol 7:589-600
Romero, Diego; Vlamakis, Hera; Losick, Richard et al. (2014) Functional analysis of the accessory protein TapA in Bacillus subtilis amyloid fiber assembly. J Bacteriol 196:1505-13
Beauregard, Pascale B; Chai, Yunrong; Vlamakis, Hera et al. (2013) Bacillus subtilis biofilm induction by plant polysaccharides. Proc Natl Acad Sci U S A 110:E1621-30
Chai, Liraz; Romero, Diego; Kayatekin, Can et al. (2013) Isolation, characterization, and aggregation of a structured bacterial matrix precursor. J Biol Chem 288:17559-68
Romero, Diego; Sanabria-Valentin, Edgardo; Vlamakis, Hera et al. (2013) Biofilm inhibitors that target amyloid proteins. Chem Biol 20:102-10
Kolodkin-Gal, Ilana; Elsholz, Alexander K W; Muth, Christine et al. (2013) Respiration control of multicellularity in Bacillus subtilis by a complex of the cytochrome chain with a membrane-embedded histidine kinase. Genes Dev 27:887-99
Bottcher, Thomas; Kolodkin-Gal, Ilana; Kolter, Roberto et al. (2013) Synthesis and activity of biomimetic biofilm disruptors. J Am Chem Soc 135:2927-30
Vlamakis, Hera; Chai, Yunrong; Beauregard, Pascale et al. (2013) Sticking together: building a biofilm the Bacillus subtilis way. Nat Rev Microbiol 11:157-68
Leiman, Sara A; May, Janine M; Lebar, Matthew D et al. (2013) D-amino acids indirectly inhibit biofilm formation in Bacillus subtilis by interfering with protein synthesis. J Bacteriol 195:5391-5
Seminara, Agnese; Angelini, Thomas E; Wilking, James N et al. (2012) Osmotic spreading of Bacillus subtilis biofilms driven by an extracellular matrix. Proc Natl Acad Sci U S A 109:1116-21

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