Abstract

Research: Staphylococcus aureus is the most common cause of cutaneous and systemic infections in both healthy individuals as well as in patients with AIDS. The skin and anterior nares are commonly colonized by S. aureus, which can be the source of life-threatening complications. However, little is understood regarding the mechanisms that this organism employs in the disease processes. The ability of bacteria to adhere to, invade into, and grow in or on mammalian cells are important initial steps in infection. This proposal addresses each of these steps by infecting primary human keratinocytes and artificial skin systems with S. aureus. Both dead deepidermized dermis and a collagen- fibroblast matrix will be utilized as dermal substrates for keratinocyte growth and differentiation. Plate assays will be utilized to determine the ability of the bacteria to survive and proliferate in the tissue culture systems. Morphologic studies using light microscopy, immunofluorescence microscopy, and electron microscopy will be utilized to determine the localization of the bacteria and the interactions with undifferentiated and differentiated keratinocytes, as well as other cellular and extracellular matrix components. To identify S. aureus virulence genes, both positive (differential fluorescence induction using the green fluorescence protein) and negative (signature-tagged mutagenesis) selection techniques will be employed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR002068-04
Application #
6374752
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Moshell, Alan N
Project Start
1999-07-01
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$116,127
Indirect Cost

  Institution

Name
Wayne State University
Department
Dermatology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Aufiero, Barbara; Guo, Meng; Young, Chen et al. (2007) Staphylococcus aureus induces the expression of tumor necrosis factor-alpha in primary human keratinocytes. Int J Dermatol 46:687-94
Aufiero, Barbara M; Talwar, Harvinder; Young, Chen et al. (2006) Narrow-band UVB induces apoptosis in human keratinocytes. J Photochem Photobiol B 82:132-9
Basturk, Olca; Khanani, Fayyaz; Sarkar, Fazlul et al. (2005) DeltaNp63 expression in pancreas and pancreatic neoplasia. Mod Pathol 18:1193-8
Aufiero, Barbara; Duanmu, Zhengbo; Guo, Meng et al. (2004) Staphylococcus aureus infection of human primary keratinocytes. J Dermatol Sci 36:173-5
Chiller, K; Selkin, B A; Murakawa, G J (2001) Skin microflora and bacterial infections of the skin. J Investig Dermatol Symp Proc 6:170-4