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)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058213-18
Application #
8916758
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Reddy, Michael K
Project Start
1998-09-01
Project End
2018-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
18
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
Shapiro, Lori R; Paulson, Joseph N; Arnold, Brian J et al. (2018) An Introduced Crop Plant Is Driving Diversification of the Virulent Bacterial Pathogen Erwinia tracheiphila. MBio 9:
Niu, Ben; Kolter, Roberto (2018) Quantification of the Composition Dynamics of a Maize Root-associated Simplified Bacterial Community and Evaluation of Its Biological Control Effect. Bio Protoc 8:
Lyons, Nicholas A; Kolter, Roberto (2018) A single mutation in rapP induces cheating to prevent cheating in Bacillus subtilis by minimizing public good production. Commun Biol 1:133
Pishchany, Gleb; Mevers, Emily; Ndousse-Fetter, Sula et al. (2018) Amycomicin is a potent and specific antibiotic discovered with a targeted interaction screen. Proc Natl Acad Sci U S A 115:10124-10129
Andrade-Domínguez, Andrés; Kolter, Roberto; Shapiro, Lori R (2018) Complete Genome Sequence of EtG, the First Phage Sequenced from Erwinia tracheiphila. Genome Announc 6:
Lyons, Nicholas A; Kolter, Roberto (2017) Bacillus subtilis Protects Public Goods by Extending Kin Discrimination to Closely Related Species. MBio 8:
Niu, Ben; Paulson, Joseph Nathaniel; Zheng, Xiaoqi et al. (2017) Simplified and representative bacterial community of maize roots. Proc Natl Acad Sci U S A 114:E2450-E2459
Andrade-Domínguez, Andrés; Kolter, Roberto (2016) Complete Genome Sequence of Pseudomonas aeruginosa Phage AAT-1. Genome Announc 4:
Segev, Einat; Castañeda, Isla S; Sikes, Elisabeth L et al. (2016) Bacterial influence on alkenones in live microalgae. J Phycol 52:125-30
Segev, Einat; Wyche, Thomas P; Kim, Ki Hyun et al. (2016) Dynamic metabolic exchange governs a marine algal-bacterial interaction. Elife 5:

Showing the most recent 10 out of 102 publications