Investigating Metabolic Control of Persister Formation in Biofilms
Annual rept. 30 Sep 2012-29 Sep 2013
TRUSTEES OF PRINCETON UNIV NEW JERSERY
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Bacterial persistence is a phenomenon in which a small fraction of a bacterial population enters dormancy in otherwise growth-promoting conditions to survive future stress. These survivors are responsible for the relapse of biofilm infections, and thus a greater understanding of their formation will lead to more effective therapies against biofilm-utilizing pathogens, such as Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. We have discovered that diauxic carbon shifts stimulate the generation of persisters in planktonic cultures, and hypothesized that metabolic transitions generate persisters in biofilms. In this project, we are identifying metabolic transitions in biofilm communities of E. coli, P. aeruginosa, and S. aureus that generate persisters, and using genetic and biochemical techniques to reconstruct the underlying signaling pathways. During this reporting period we discovered that specific carbon source transitions in E. coli biofilms stimulate persister formation through a ppGpp and nucleoid-associated protein dependent pathway. In addition, preliminary data suggests that nitrogen source transitions in P. aeruginosa biofilms and carbon source transitions in S. aureus biofilms stimulate persister formation. Further, we have developed a rapid method to assay persister metabolic activity. Support from this grant has led to three publications and one submitted manuscript thus far.
- Medicine and Medical Research