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Quirky Lyme Disease Bacteria: Unlike Most Organisms, They Don't Need Iron, but Crave Manganese
Saito collaborated with biomedical researchers at Johns Hopkins University, applying his proteomic techniques to explore proteins in a terrestrial organism, the bacteria that cause Lyme Disease. Unlike all other known organisms, Borrelia burgdorferi need manganese (blue dot), rather than iron, to serve as linchpins bonded into key enzymes. The scientists found that to cause disease, Borrelia require unusually high levels of manganese. The findings open new avenues to search for ways to attack the bacteria. (Credit: Illustration by P. John Hart, University of Texas)
Mar. 21, 2013 � Scientists have confirmed that the pathogen that causes Lyme Disease -- unlike any other known organism -- can exist without iron, a metal that all other life needs to make proteins and enzymes. Instead of iron, the bacteria substitute manganese to make an essential enzyme, thus eluding immune system defenses that protect the body by starving pathogens of iron.
To cause disease, Borrelia burgdorferi requires unusually high levels of manganese, scientists at Johns Hopkins University (JHU), Woods Hole Oceanographic Institution (WHOI), and the University of Texas reported. Their study, published March 22, 2013, in The Journal of Biological Chemistry, may explain some mysteries about why Lyme Disease is slow-growing and hard to detect and treat. The findings also open the door to search for new therapies to thwart the bacterium by targeting manganese.
"When we become infected with pathogens, from tuberculosis to yeast infections, the body has natural immunological responses," said Valeria Culotta, a molecular biologist at the JHU Bloomberg School of Public Health. The liver produces hepcidin, a hormone that inhibits iron from being absorbed in the gut and also prevents it from getting into the bloodstream. "We become anemic, which is one reason we feel terrible, but it effectively starves pathogens of iron they need to grow and survive," she said.
Borrelia, with no need for iron,has evolved to evade that defense mechanism. In 2000, groundbreaking research on Borrelia's genome by James Posey and Frank Gherardini at the University of Georgia showed that the bacterium has no genes that code to make iron-containing proteins and typically do not accumulate any detectable iron.
Culotta's lab at JHU investigates what she called "metal-trafficking" in organisms� -- the biochemical mechanisms that cells and pathogens such as Borrelia use to acquire and manipulate metal ions for their biological purposes.
"If Borrelia doesn't use iron, what does it use?" Culotta asked.
To find out, Culotta's lab joined forces with Mak Saito, a marine chemist at WHOI, who had developed techniques to explore how marine life uses metals. Saito was particularly intrigued because of the high incidence of Lyme Disease on Cape Cod, where WHOI is located, and because he specializes in metalloproteins, which contain iron, zinc, cobalt, and other elements often seen in vitamin supplements. The metals serve as linchpins, binding to enzymes. They help determine the enzymes' distinctive three-dimensional shapes and the specific chemical reactions they catalyze.
It's difficult to identify what metals are within proteins because typical analyses break apart proteins, often separating metal from protein. Saito used a liquid chromatography mass spectrometer to distinguish and measure separate individual Borrelia proteins according to their chemical properties and infinitesimal differences in their masses. Then he used an inductively coupled plasma mass spectrometer to detect and measure metals down to parts per trillion. Together, the combined analyses not only measured the amounts of metals and proteins, they showed that the metals are components of the proteins.
"The tools he has are fantastic," Culotta said. "Not too many people have this set of tools to detect metalloproteins."
The experiments revealed that instead of iron, Borrelia uses that element's next-door neighbor on the periodic chart, manganese, in certain Borrelia enzymes. These include an amino peptidase and an important antioxidant enzyme called superoxide dismutase.
Superoxide dismutase protects the pathogens against a second defense mechanism that the body throws against them. The body bombards pathogens with superoxide radicals, highly reactive molecules that cause damage within the pathogens. Superoxide dismutase is like an antioxidant that neutralizes the superoxides so that the pathogens can continue to grow.
The discoveries open new possibilities for therapies, Culotta said. "The only therapy for Lyme Disease right now are antibiotics like penicillin, which are effective if the disease is detected early enough. It works by attacking the bacteria's cell walls. But certain forms of Borrelia, such as the L-form, can be resistant because they are deficient in cell walls."
"So we'd like to find targets inside pathogenic cell that could thwart their growth," she continued. "The best targets are enzymes that the pathogens have, but people do not, so they would kill the pathogens but not harm people." Borrelia's distinctive manganese-containing enzymes such as superoxide dismutase may have such attributes.
In search of new avenues of attack, the groups are planning to expand their collaborative efforts by mapping out all the metal-binding proteins that Borellia uses and investigating biochemical mechanisms that the bacteria use to acquire manganese and directs it into essential enzymes. Knowing details of how that happens offers ways to disrupt the process and deter Lyme Disease.
The authors of the new study are J. Daphne Aguirre, Hillary Clark, Christine Vazquez, Shaina Palmere, and Culotta (JHU Bloomberg School of Public Health); Saito and Matthew McIlvin (WHOI); Denise Grab (JHS School of Medicine); Janakiram Seshu (University of Texas); and P. John Hart (University of Texas Health Science Center).
Posts: 789 | From CT, | Registered: Jun 2006
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This research is quite interesting. If the body naturally starves pathogens of iron to kill them and we feel sick because of it, can the same principal be applied to manganese and Lyme? This is not a suggestion, it's a question.
Interestingly, Magnesium Deficiency has been linked to Myasthenia Gravis. I've had five episodes that prompted three doctors to suggest that I be tested for Myasthenia. Whether this is a true Myasthenia or a Myasthenia syndrome is uncertain. Now that I know I have Lyme disease, this makes sense. When the body deprives itself of iron, it makes us sick. When the Lyme deprives us of manganese, for it's survival, it makes us sick. There are several symptoms of magnesium deficiency, other than Myasthenia or Myasthenia syndrome, including depression.
While it's true the body doesn't naturally starve the Lyme from manganese, we now know it's because it's natural immune intelligence is tricked. Is it possible that starving the body of magnesium would help kill the Lyme? I don't know what, but it seems like this could do other damage to the body. It seems to me that it is worth further investigation.
-------------------- I'm not there yet but I'm closer than I was yesterday.---- Lyme Band 31,41,58. Being treated for Lyme and Bartonella. Posts: 149 | From Maine | Registered: Oct 2010
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poppy
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Very interesting. Thanks for posting.
Some people have suggested depriving patients of elements that borrelia use, such as magnesium. This just causes the patient grief. So, I am doubting that manganese deprivation will work either. However, this article suggests some other possibilities, which I hope will be followed up. We really need honest useful research like this work, not endless foot dragging, outright lies, and figuring out how lyme infection happens. What about all the people who are already infected....this does not help them.
Posts: 2888 | From USA | Registered: Mar 2004
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Here is an article outlining some of the effects on the body of inadequate manganese. http://www.tldp.com/issue/180/Clinical%20Effects%20of%20Mn.html Myasthenia is serious and long term, survival is not expected beyond five years without treatment. With treatment a person can live a normal life span.
These are not suggestions. I'm not a doctor or biochemist. I just found the information interesting.
-------------------- I'm not there yet but I'm closer than I was yesterday.---- Lyme Band 31,41,58. Being treated for Lyme and Bartonella. Posts: 149 | From Maine | Registered: Oct 2010
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It would be expected that depriving the body of any essential nutrient would have ramifications. I found it interesting that the body does exactly that and we suffer the ramifications and then get better. I would love to see more information and research on this, particularly in vitro research. Any medications designed around this model would have to be carefully controlled as well due to potential toxin overload.
-------------------- I'm not there yet but I'm closer than I was yesterday.---- Lyme Band 31,41,58. Being treated for Lyme and Bartonella. Posts: 149 | From Maine | Registered: Oct 2010
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poppy
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You're right. They might be able to do this short term, but what if they would have to do it long term for chronic cases?
Posts: 2888 | From USA | Registered: Mar 2004
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I have chronic Lyme. After reading the links on magnesium here I can see how important magnesium is to human metabolism. This is a great site to become educated.
-------------------- I'm not there yet but I'm closer than I was yesterday.---- Lyme Band 31,41,58. Being treated for Lyme and Bartonella. Posts: 149 | From Maine | Registered: Oct 2010
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