The growth of staphylococci can be inhibited by aportransferrin, the serum iron-binding protein. Presumably, growth during human infections is also dependent on the ability of staphylococci to acquire iron from the host. Although previous research has examined the mechanisms by which gram-negative organisms acquire iron, little work has been done to elucidate the mechanisms used by gram-positive organisms. For decades, Staphylococcus aureus has been an important cause of community- and hospital-acquired bloodstream infections. Recently Staphylococcus epidermidis has become one of the most common causes of nosocomial bloodstream infections. Yet little is known about the mechanisms by which staphylococci compete with apotransferrin. The long-term objective of the proposal is to develop a comprehensive picture of the mechanisms by which staphylococci acquire iron. Assays of (55)Fe uptake from various substrates, including apotransferrin, will be used to determine which serve as iron sources. Mechanisms used by other bacteria will be evaluated to determine whether they have a role in iron acquisition by staphylococci: bacterial iron chelators (siderophores), bacterial reductases, bacteria- or host-derived organic acids. Mechanisms used by S. aureus will be compared and contrasted with those used by the less virulent staphylococcal species. The Clinical Investigator Award will enable the Principal Investigator (PI) to address critical questions regarding the pathogenesis of staphylococcal infections. The data will give important insights into the differences between infections caused by S. aureus and by less virulent staphylococcal species. The goal is to develop the antibacterial activity of iron deprivation into new approaches for the prevention and treatment of staphylococcal infections. In addition, the PI will gain experience essential for her future career as an independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AI001032-01
Application #
3078884
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1991-09-01
Project End
1994-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242