Although a diverse arsenal of antimicrobial drugs has been developed, bacterial and fungal infections remain prevalent worldwide. The formation of multicellular communities of microbes, called biofilms, is a common feature of these diseases that contributes to their endurance. Cells in biofilms are held together by an extracellular matrix and differ from those grown in liquid cultures with respect to their metabolism and sensitivity to antimicrobial drugs. Our long-term goal is to define the integrated, redox-based regulatory networks and metabolisms that support survival of bacteria in biofilms, with a focus on the pathogen Pseudomonas aeruginosa. We hypothesize that the changing redox states of cells in developing biofilms affect multicellular behavior, virulence, and susceptibility to antibiotics. A standardized colony biofilm morphology assay facilitates our investigation of mechanisms that underpin biofilm-specific metabolism and feature formation. We will use basic molecular approaches combined with newly developed and innovative techniques, including electrochemical and microscopic analysis of biofilms at the micron scale, to address fundamental questions regarding the use of redox-active substrates for metabolism and the global regulation of biofilm matrix in response to redox cues: (1) How does P. aeruginosa balance its cellular redox state in the oxygen- limited regions of biofilms? (2) How does redox control of cellular signaling determine overall community morphology and cellular arrangement within the biofilm? (3) How does the use of pyruvate and lactate, important energy sources and metabolic intermediates, contribute to survival in biofilms and metabolism during host infection? As P. aeruginosa is a major cause of infections in hospitals and in patients with cystic fibrosis, we are motivated by the potential for these mechanisms to serve as therapeutic targets.

Public Health Relevance

The formation of biofilms, communities of cells that are held together by a matrix, is a common feature of bacterial infections that enhances their resistance to treatments. We study the mechanisms that (1) allow biofilms to sense and respond to environmental conditions and (2) support cellular energy generation and growth in biofilms. This work will uncover potential targets for treatment and may reveal basic aspects of biofilm physiology that are relevant for many types of bacteria.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Lu, Kristina
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Graduate Schools
New York
United States
Zip Code
Cornell, William C; Morgan, Chase J; Koyama, Leslie et al. (2018) Paraffin Embedding and Thin Sectioning of Microbial Colony Biofilms for Microscopic Analysis. J Vis Exp :
Lin, Yu-Cheng; Cornell, William Cole; Jo, Jeanyoung et al. (2018) The Pseudomonas aeruginosa Complement of Lactate Dehydrogenases Enables Use of d- and l-Lactate and Metabolic Cross-Feeding. MBio 9:
Sporer, Abigail J; Beierschmitt, Christopher; Bendebury, Anastasia et al. (2018) Pseudomonas aeruginosa PumA acts on an endogenous phenazine to promote self-resistance. Microbiology 164:790-800
Lin, Yu-Cheng; Sekedat, Matthew D; Cornell, William Cole et al. (2018) Phenazines regulate Nap-dependent denitrification in Pseudomonas aeruginosa biofilms. J Bacteriol :
Arnaouteli, Sofia; Ferreira, Ana Sofia; Schor, Marieke et al. (2017) Bifunctionality of a biofilm matrix protein controlled by redox state. Proc Natl Acad Sci U S A 114:E6184-E6191
Jo, Jeanyoung; Cortez, Krista L; Cornell, William Cole et al. (2017) An orphan cbb3-type cytochrome oxidase subunit supports Pseudomonas aeruginosa biofilm growth and virulence. Elife 6:
Yan, Jinyuan; Deforet, Maxime; Boyle, Kerry E et al. (2017) Bow-tie signaling in c-di-GMP: Machine learning in a simple biochemical network. PLoS Comput Biol 13:e1005677
Sporer, Abigail J; Kahl, Lisa J; Price-Whelan, Alexa et al. (2017) Redox-Based Regulation of Bacterial Development and Behavior. Annu Rev Biochem 86:777-797
Fong, Jiunn Cn; Rogers, Andrew; Michael, Alicia K et al. (2017) Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. Elife 6:
Maderbocus, Riyaz; Fields, Blanche L; Hamilton, Keith et al. (2017) Crystal structure of a Pseudomonas malonate decarboxylase holoenzyme hetero-tetramer. Nat Commun 8:160

Showing the most recent 10 out of 22 publications