Staphylococcus aureus is a gram positive, ubiquitous bacterial species, with the predominant reservoir in nature being humans. The increased use of implanted medical devices such as intramedullary rods, screws, plates, and artificial joints has provided a physiological niche for microbes to cause infections. While a number of bacterial species may cause microbial fouling of indwelling medical devices, S. aureus causes a majority of these infections, producing high chronicity, morbidity, and mortality. One of the important mechanisms by which S. aureus is able to cause persistent infections on indwelling medical devices is through colonizing and synthesizing a """"""""slime"""""""" layer, termed the glycocalyx or biofilm. This layer prevents infection resolution by antimicrobial agents and host phagocytic cells. Once an implant is colonized and chronic infection ensues, the standard treatment option is implant removal. This proposal seeks to identify S. aureus gene products with upregulated production in biofilms using two dimensional (2D) gel electrophoresis. Selected up-regulated proteins will then be evaluated, first, for their ability to be recognized by the host immune system during an in vivo biofilm infection, and second, for their protective efficacy in preventing infections in an implant-associated infection model in rabbits. The data generated here may contribute to the eventual development of a vaccine against S. aureus biofilms infections in humans. In addition, this proposal will also contribute to a more complete understanding of the bacterial factors involved in S. aureus biofilm formation and maturation. This understanding will enable one to create novel materials, surfaces, and/or disinfection strategies that resist or eliminate staphylococcal fouling and biofilm formation. Also, the proteome will be compared to transcriptome DMA microarray studies already completed in the Pi's laboratory in order to determine the global interrelation between gene expression and protein production for S. aureus biofilms grown under flow, thereby allowing staphylococci to be understood at a new level. Lastly, the results obtained in the evaluation of S. aureus biofilm formation may be used as a model for the biofilm formation by other closely related gram positive bacterial species, including Streptococcus spp., Listeria spp., Clostridium spp. and Bacillus spp. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI069568-02
Application #
7423938
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Perdue, Samuel S
Project Start
2007-06-01
Project End
2012-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
2
Fiscal Year
2008
Total Cost
$364,196
Indirect Cost
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Deng, Yang; Liu, Junyan; Peters, Brian M et al. (2015) Antimicrobial resistance investigation on Staphylococcus strains in a local hospital in Guangzhou, China, 2001-2010. Microb Drug Resist 21:102-4
Schlecht, Lisa Marie; Peters, Brian M; Krom, Bastiaan P et al. (2015) Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue. Microbiology 161:168-181
Achermann, Yvonne; Tran, Bao; Kang, Misun et al. (2015) Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model. Clin Vaccine Immunol 22:467-76
Jarrett, Angela M; Cogan, N G; Shirtliff, M E (2015) Modelling the interaction between the host immune response, bacterial dynamics and inflammatory damage in comparison with immunomodulation and vaccination experiments. Math Med Biol 32:285-306
Kong, Eric F; Kucharíková, Sona; Van Dijck, Patrick et al. (2015) Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease. Infect Immun 83:604-13
Arnold, William V; Shirtliff, Mark E; Stoodley, Paul (2014) Bacterial biofilms and periprosthetic infections. Instr Course Lect 63:385-91
Freiberg, Jeffrey A; McIver, Kevin S; Shirtliff, Mark E (2014) In vivo expression of Streptococcus pyogenes immunogenic proteins during tibial foreign body infection. Infect Immun 82:3891-9
Sternberg, Claus; Bjarnsholt, Thomas; Shirtliff, Mark (2014) Methods for dynamic investigations of surface-attached in vitro bacterial and fungal biofilms. Methods Mol Biol 1147:3-22
McConoughey, Stephen J; Howlin, Rob; Granger, Jeff F et al. (2014) Biofilms in periprosthetic orthopedic infections. Future Microbiol 9:987-1007
Lourenço, Anália; Coenye, Tom; Goeres, Darla M et al. (2014) Minimum information about a biofilm experiment (MIABiE): standards for reporting experiments and data on sessile microbial communities living at interfaces. Pathog Dis 70:250-6

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