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Research

My research group utilizes the model organism Pseudomonas aeruginosa to elucidate regulatory and signaling events underlying the formation and development of highly antimicrobial resistant biofilms. Specifically, we are interested differential gene expression coinciding with the formation and dispersion of biofilms, the role of posttranslational modifications in enabling bacteria to sense and respond to environmental conditions, and the mechanism by which biofilm cells gain their heightened resistance to antimicrobial agents. The overall goal of our research to identify factors to control and manage biofilms and their extraordinary resistance to antimicrobial agents.

Research Projects

Biofilm development

A biofilm constitutes an alternative lifestyle in which bacteria adopt a multicellular (community) behavior that facilitates and/or prolongs survival in diverse environmental niches. The formation of a biofilm begins with the attachment of free-floating (single) bacteria to a surface. But then what? How do bacteria build these elaborate 3-dimensional, multicellular  communities known as biofilms?

 

Previous research in our laboratory has shown that the formation of biofilms is a regulated and sequential process.  Using this knowledge, current research aims at elucidating downstream regulatory events and processes that occur at the different stages of biofilm development, identifying key factors that are required for  biofilm formation in a strain-independent manner, and metabolic pathways unique to biofilms.

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Biofilm Drug Tolerance

Bacterial cells within biofilms exhibit elevated levels of tolerance towards antimicrobial agents. In fact, biofilm cells can be up to 1000-fold less susceptible to various antibiotics than their planktonic counterparts. This characteristic contributes to biofilms and biofilm infections being difficult to eradicate via conventional treatment regimens. 

 

In Pseudomonas aeruginosa, biofilm drug tolerance is linked to biofilm development, with transition to the irreversible attachment stage coinciding with attached cells gaining their heightened drug tolerance.

 

We are interested in elucidating the mechanism contributing to the switch from a susceptible to a drug tolerant state. Ongoing research focuses on the role of two proteins in biofilm tolerance, the  membrane-bound protein SagS and the transcriptional regulator BrlR.

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Biofilm Dispersion

Dispersion is a regulated process by which biofilm bacteria liberate themselves from the matrix-encased biofilms and transition to the planktonic, free-living state. Dispersion of P. aeruginosa biofilms occurs in response to a wide variety of  cues including carbon sources, nitric oxide, and other environmental cues.

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We are interested in this dispersion as bacterial cells that dispersed from the biofilm are more susceptible to antimicrobial agents than the biofilm they evacuated.

 

Current reserach aims at elucidating 

  • Signal transduction of dispersion cues into a dispersion response

  • the role of the signaling molecule c-di-GMP in the dispersion response

  • how bacteria liberate themselves from the biofilm

  • changes in the transcriptome of dispersing bacteria

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