Otitis media (OM) is the most common reason that an American child receives antibiotics or undergoes a general anesthetic. OM is the leading cause of pediatric hearing loss and can lead to language, speech and behavioral problems. OM disproportionately affects children of color and hinders the full participation of women in the workforce. In this continuation application, we propose to extend our paradigm-shifting discovery that chronic OM is actually a biofilm illness. The Center for Genomic Sciences and the Center for Biofilm Engineering have a 6-year history of collaborative effort, and have published the results in Science, JAMA, and Scientific American. In the first phase of these investigations we developed expertise with both novel biological reagents and the construction and operationalization of extensive new facilities and instrumentation platforms. The results of these led to the development of a new overarching theoretical construct, termed Bacterial Plurality, which states that chronic bacterial pathogenesis and persistence reside at the population level rather than within individual bacterium. In this continuation, we will be applying cutting edge technology focused by a new theoretical understanding of chronic infections to provide a global framework for understanding persistent Pseudomonas aeruginosa (PA)-induced chronic OM and otorrhea. The goals of the proposed work are: 1) to study the genetic interplay between the host mucosa and a mucosal biofilm in our PA-induced chronic OM chinchilla model; 2) test the theory of bacterial plurality using an evolutionary fitness model. Using the multi-platform, massively parallel, integrated systems developed during the first grant cycle, we will quantitate the degree of genomic plasticity by direct genome sequencing of PA, and divine the extent of variation in gene expression among the many bacterial envirovars that these organisms can adopt. A discovery that has immediate clinical relevancy is that biofilm antibiotic resistance is mediated largely by bacterial metabolic resistance owing to limiting nutrient conditions within the core of the biofilms. ? ?

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Watson, Bracie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Allegheny-Singer Research Institute
United States
Zip Code
Swearingen, Matthew C; Mehta, Ajeet; Mehta, Amar et al. (2016) A novel technique using potassium permanganate and reflectance confocal microscopy to image biofilm extracellular polymeric matrix reveals non-eDNA networks in Pseudomonas aeruginosa biofilms. Pathog Dis 74:ftv104
Rudkjøbing, Vibeke Børsholt; Thomsen, Trine Rolighed; Xu, Yijuan et al. (2016) Comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections. BMC Infect Dis 16:652
Ahmed, Azad; Earl, Josh; Retchless, Adam et al. (2012) Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J Bacteriol 194:3922-37
Hu, Fen Z; Eutsey, Rory; Ahmed, Azad et al. (2012) In vivo capsular switch in Streptococcus pneumoniae--analysis by whole genome sequencing. PLoS One 7:e47983
Nistico, L; Kreft, R; Gieseke, A et al. (2011) Adenoid reservoir for pathogenic biofilm bacteria. J Clin Microbiol 49:1411-20
Boissy, Robert; Ahmed, Azad; Janto, Benjamin et al. (2011) Comparative supragenomic analyses among the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae using a modification of the finite supragenome model. BMC Genomics 12:187
Davie, Jeremiah J; Earl, Josh; de Vries, Stefan P W et al. (2011) Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates. BMC Genomics 12:70
Hiller, N Luisa; Eutsey, Rory A; Powell, Evan et al. (2011) Differences in genotype and virulence among four multidrug-resistant Streptococcus pneumoniae isolates belonging to the PMEN1 clone. PLoS One 6:e28850
Kerschner, Joseph E; Erdos, Geza; Hu, Fen Ze et al. (2010) Partial characterization of normal and Haemophilus influenzae-infected mucosal complementary DNA libraries in chinchilla middle ear mucosa. Ann Otol Rhinol Laryngol 119:270-8
Kathju, Sandeep; Lasko, Leslie-Ann; Nistico, Laura et al. (2010) Cutaneous fistula from the gastric remnant resulting from a chronic suture-associated biofilm infection. Obes Surg 20:251-6

Showing the most recent 10 out of 50 publications