Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes chronic lung infections associated with biofilm formation in the airways of cystic fibrosis (CF) and immune-compromised patients, including those with chronic wounds. Biofilms are structured communities of microbes encased within a matrix and exhibit resistance to antimicrobials and host defenses. It remains unclear how biofilm bacteria survive within the CF airways or the interplay of P. aeruginosa matrix materials with host immune cells. The focus of this application is on two critical components of the P. aeruginosa biofilm matrix biofilm matrix, an extracellular polysaccharide Psl and a protein adhesion CdrA. Our overall objective is to determine the roles of Psl and CdrA in biofilm structural integrity and tolerance o P. aeruginosa to antimicrobials and host defense.
Aim 1 will focus investigating structure- function relationships necessary for P. aeruginosa biofilm matrix integrity and define the roles of biofilm matrix components in modulating interactions of P. aeruginosa with human phagocytic cells. In the second aim we will define a novel signal transduction pathway responsible for a feed-forward mechanism of Psl-dependent signaling. There remain significant gaps in our understanding of how P. aeruginosa survive in the CF airway even in the presence of a robust immune response. Since the biofilm matrix provides a protective role, studies aimed at understanding the functions of matrix components will provide insights and therapeutic strategies aimed at early events of CF pathogenesis and other P. aeruginosa infections where biofilms are linked with human disease.

Public Health Relevance

Pseudomonas aeruginosa is a versatile opportunistic pathogen that can cause chronic pulmonary infection in cystic fibrosis (CF) patients and is also a key source of infection in immune-compromised patients. Within the CF airway, P. aeruginosa transforms into a resistant community called a biofilm. Inside the biofilm community, bacteria aggregate and cover themselves with a coating composed of sugar molecules (exopolysaccharides) and proteins. This application will define how these molecules provide structural integrity to the biofilm and how this relates to the recalcitrance of biofilm bacteria t host defenses. We will also define how one component of the biofilm matrix serves as a signaling molecule to communicate with other members of the biofilm community. The ultimate goal of the research is to enhance the interaction of host immune cells and biofilm forming P. aeruginosa so that biofilms can be eradicated from the CF lung as well as individuals with other P. aeruginosa infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI097511-01A1
Application #
8506656
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Taylor, Christopher E,
Project Start
2013-01-01
Project End
2017-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$373,354
Indirect Cost
$89,363
Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Roy, Sashwati; Elgharably, Haytham; Sinha, Mithun et al. (2014) Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol 233:331-43