The long-term objective of this project is to characterize the properties of staphylococcal biofilms that account for their resistance to antimicrobial chemotherapy. S. aureus is an important cause of biofilm-related infections such as native valve endocarditis, osteomyelitis, and medical device-related infections. Infections involving staphylococcal biofilms are often very difficult to treat with antibiotics and may be recurrent. The characteristics of biofilms that make them refractory to antibiotic therapy are not well understood at this time. In this study the role of gene regulation or """"""""transcriptional adaptation"""""""" in the resistance of biofilms to antibiotics will be analyzed. One untested possibility is that biofilms are more resistant to antibiotics than planktonic cells because they are """"""""hyper-adaptable"""""""" or uniquely poised to respond to stressful environmental conditions through the rapid transcriptional activation of stress-related genes. An alternative hypothesis is that cells within a biofilm have more time to respond at the transcriptional level to antibiotics than do their planktonic counterparts due to diffusion limitations imparted by the exopolysaccharide matrix. Both of these hypotheses challenge the common notion that the properties that make biofilms resistant to antibiotics are constitutive rather than induced following antibiotic exposure. In order to test these hypotheses, a global screen of genes activated in planktonic cells and biofilms in response to antibiotics from three distinct classes will be conducted by microarray analysis. Genes that are significantly induced or repressed in response to antibiotic treatment will be further characterized by mutagenesis. It is hoped that a better understanding of the mechanism of antibiotic resistance of biofilms will advance the development of therapies used to combat these infections and it is expected that these studies will increase our current knowledge of the regulation of the stress response. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
5K22AI062945-02
Application #
7227426
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Perdue, Samuel S
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2007
Total Cost
$108,000
Indirect Cost
Name
Virginia Commonwealth University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298