Ear infections (otitis media, or OM) are the most common illness for which children visit a physician, receive antibiotic prescriptions, and undergo surgery, with a cost of over 5 billion dollars annually. Most children in the U.S. are treated with antibiotics, accounting for 25% of all such prescriptions nationally, and this widespread antibiotic use has led to the development of antibiotic-resistant bacterial strains. OM results from an interplay of genetic and environmental factors, but is primarily an infectious process, and our contribution has been to show that OM is a biofilm disease.
Biofilms are complex organized communities of attached bacteria embedded in an extracellular matrix that display many of the hallmarks of multicellular organisms including: small molecule intercellular communication systems; specialized phenotypes; and differentiated metabolism. Biofilms can be composed of a single species or of multiple species. Confocal laser scanning microscopy (CLSM) of biofilms has revealed the 3-D structure of biofilms and demonstrated that the bacteria live in matrix-enclosed cellular towers separated by open water channels which act as a primitive circulatory system for the delivery of nutrients and removal of metabolic waste products. The CDC estimates that > 60% of bacterial infections in the U.S. are biofilm-related.
Our Center for Genomic Sciences has had a long-standing interest in biofilms, and have a series of inter-related RO1’s to study biofilm formation of Streptococcus pneumoniae, Hemophilus influenzae and Pseudomonas aureginosa as they relate to ear infections. (Sp)-associated otitis media with effusion (OME) was a mucosal biofilm disease. While we are studying the basic science aspects of biofilms, to include whole genome sequencing and biofilm structural analysis, one of our main efforts is to identify clinically-useful strategies to disrupt and prevent biofilms in vivo. We are using three novel approaches to treat and prevent chronic ear infections: 1) anti- S. pneumoniae-specific Specifically Targeted Anti-Microbial Peptides (STAMP) technology, which employs a bifunctional synthetic peptide for species-specific recognition and killing, thus providing a ‘magic bullet’ that spares normal microbial flora; 2) development of a novel peptide-based anti- S. pneumoniae vaccine that would protect against all strains of S. pneumoniae; and 3) techniques to disrupt the biofilm matrix. To accomplish these goals, we have assembled a world-class team of collaborators: Professor Wenyuan Shi at UCLA, who has produced a STAMP against S. mutans and Dr. Peter Nara of Biological Mimetics for the vaccine work. The beauty of these approaches is that they address one of our major public health issues: the development of highly-drug-resistant strains of bacteria from the overuse of antibiotics, particularly in the treatment of ear disease.
Selected Publications (See James Christopher Post's publications in PubMed.)
"Chronic surgical site infection due to suture-associated polymicrobial biofilm"
Kathju S, Nistico L, Hall-Stoodley L, Post JC, Ehrlich GD, and Stoodley P
Surgical Infections, Accepted, 2009
"Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model"
Shen K, Krakora SM, Cunningham M, Singh M, Wang X, Hu FZ, Post JC, and Ehrlich GD
Orthodontics and Craniofacial Research, 12: 254-262, 2009
"Gene expression differences in infected and non-infected middle ear complementary DNA libraries"
Kerschner JE, Horsey E, Ahmed A, Erbe C, Khampang P, Cioffi J, Hu FZ, Post JC, and Ehrlich GD
Archives of Otolaryngology-Head & Neck Surgery, 135(1): 33-39, 2009
"Characterization of biofilm matrix, degradation by DNase treatment and evidence of capsule downregulation in Streptococcus pneumoniae clinical isolates"
Hall-Stoodley L, Nistico L, Sambanthamoorthy K, Dice B, Nguyen D, Mershon WJ, Johnson C, Hu FZ, Stoodley P, Ehrlich GD, and Post JC
BMC Microbiology, 8: 173, 2008
"Biofilms in nephrology"
Marcus RJ, Post JC, Stoodley P, Hall-Stoodley L, McGill RL, Sureshkumar KK, and Gahlot V
Expert Opinion on Biological Therapy, 8;8: 1159-1166, 2008
"Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis"
Buchinsky FJ, Donfack J, Derkay CS, Choi SS, Conley SF, Myer III CM, McClay JE, Campisi P, Wiatrak BJ, Sobol SE, Schweinfurth JM, Tsuji DH, Hu FZ, Rockette HE, Ehrlich GD, and Post JC
PLoS ONE, 3(5): e2263, 2008
"Differential expression of chaperonin containing T-complex polypeptide (CCT) subunits during fetal and adult skin wound healing"
Satish L, Abdulally A, Oswald D, Johnson S, Hu FZ, Post JC, Ehrlich GD, and Kathju S
Cell Stress Chaperones, 13: 527-533, 2008
"Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture"
Satish L, LaFramboise WA, O'Gorman DB, Johnson S, Janto B, Gan BS, Baratz ME, Hu FZ, Post JC, Ehrlich GD, and Kathju S
BMC Medical Genomics, 1: 10, 2008
"Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media"
Forbes ML, Horsey E, Hiller NL, Buchinsky FJ, Hayes JD, Compliment JM, Hillman T, Ezzo S, Shen K, Keefe R, Barbadora K, Post JC, Hu FZ, and Ehrlich GD
PLoS ONE, 3(4): e1969, 2008
"Clinical revenue investment in biomedical research"
Post JC
Journal of the American Medical Association, 298(14): 1637, 2007
"The role of biofilms in otolaryngologic infections: update 2007"
Post JC, Hiller NL, Nistico L, Stoodley P, and Ehrlich GD
Current Opinion in Otolaryngology & Head and Neck Surgery, 15(5): 347-351, 2007
"Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome"
Hiller NL, Janto B, Hogg JS, Boissy R, Yu S, Powell E, Keefe R, Ehrlich NE, Shen K, Hayes J, Barbadora K, Klimke W, Dernovoy D, Tatusova T, Parkhill J, Bentley SD, Post JC, Ehrlich GD, and Hu FZ
Journal of Bacteriology, 189(22): 8186-8195, 2007
"Virulence phenotypes of low-passage clinical isolates of nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media"
Buchinsky FJ, Forbes ML, Hayes JD, Shen K, Ezzo S, Compliment J, Hogg J, Hiller NL, Hu FZ, Post JC, and Ehrlich GD
BMC Microbiology, 7: 56, 2007
"Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains"
Hogg JS, Hu FZ, Janto B, Boissy R, Hayes J, Keefe R, Post JC, and Ehrlich GD
Genome Biology, 8(6): R103, 2007
"Gene expression changes in peripheral blood mononuclear cells from multiple sclerosis patients undergoing beta-interferon therapy"
Singh MK, Scott TF, LaFramboise WA, Hu FZ, Post JC, and Ehrlich GD
Journal of the Neurological Sciences, 258(1-2): 52-59, 2007
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