The Borrelia burgdorferi pathogen for Lyme disease represents a continuing problem in public health. The spirochete can persist in a host in spite of a strong immune response, often undetected for extended periods. One clever adaption is B. burgdorferi's ability to thwart the intense iron starvation response of innate immunity. While most pathogens require host iron for survival, B. burgdorferi has evolved with no known requirement for iron and can thrive in culture without detectable cellular iron. Instead of iron, the pathogen requires manganese for virulence as shown by Norgard and colleagues. Our research program has a long-term focus on the biology of manganese and the effects of competing pools of cellular iron. As such, B. burgdorferi represented an intriguing organism for our comparative studies of manganese physiology. While most microorganisms accumulate trace levels of manganese compared to intracellular iron, B. burgdorferi is capable of accumulating extraordinarily high levels of manganese without any signs of toxicity. In spite of its tolerance t high intracellular manganese, the spirochete cannot tolerate even small increments in extracellular manganese. This potent inhibitory effect of manganese involves manganese interactions with a component in serum and toxicity correlates with uptake of iron, not manganese into the cell. The mechanism by which elevations in serum manganese can increase bioavailability of iron and cause growth inhibition of B. burgdorferi is the focus of this proposal. Through candidate molecule and biochemical fractionation approaches, we seek to isolate the serum factor(s) responsible for B. burgdorferi growth inhibition and iron uptake with low manganese. We will also investigate whether the iron accumulated interferes with normal metal-protein partnerships in B. burgdorferi, including select manganese containing enzymes. This self- contained two year study will shed new light into how manganese-iron interactions can affect the physiology of an important pathogen.

Public Health Relevance

The Borrelia burgdorferi pathogen for Lyme disease represents a continuing problem in public health, largely due to its ability to persist undetected n a human host. We are exploring how components of serum, including metals such as manganese and iron can control the growth of this organism. These studies can have important implications for pathogenicity of Borrelia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI109297-01
Application #
8620281
Study Section
Special Emphasis Panel (ZRG1-IDM-B (80))
Program Officer
Breen, Joseph J
Project Start
2014-06-15
Project End
2016-05-31
Budget Start
2014-06-15
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$81,000
Indirect Cost
$31,000
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218