Why Bacteria (Usually) Thrive on Iron
Iron is an essential metal for many bacterial organisms to make proteins and enzymes and, thus, to survive. During periods of infection, our bodies are pretty adept at sequestering iron in order to starve these bacteria and slow down their process of replication, thus making infection easier to fight off. Researchers at Johns Hopkins University, the University of Texas and Woods Hole Oceanographic Institute published a study last week describing the peculiar affinity of Lyme disease bacteria for manganese, rather than iron and their findings could help explain why tests and treatments for Lyme disease remain problematic. It could also lead to the creation of new drugs for Lyme disease treatment that work by starving the bacteria of much-needed growth elements instead of trying to rely on attacking their cell walls, which doesn’t always work when the Lyme disease bacteria are cell wall-deficient L-forms resistant to such antibiotics.
How Anaemia and Infection are Connected
During their research, the scientists looked at how yeast infections, tuberculosis and other pathogens spread in the human body and how our natural defences work to eradicate them. One method is the production of a hormone in the liver, hepcidin, that blocks iron absorption from the gut and, therefore, prevents it from entering the bloodstream in any significant quantity. This induces a (hopefully) temporary anaemia but is usually quite effective in starving the bacterial invader of iron and thus rendering it less able to become a serious infection. This does not work for Lyme disease bacteria however, meaning that a patient may have all the symptoms of a chronic iron-deficiency anaemia in addition to the symptoms of Borreliosis itself.
Iron, Zinc, and Manganese in Lyme Disease Bacteria
As far back as 2000, Lyme disease researchers Posey and Gherardini recognized that the bacterium did not seem to horde iron as other bacteria do, nor did Borrelia have genes that coded for iron-containing proteins. This led scientists to wonder which metal(s) the Lyme disease bacteria did use as metal-trafficking in such organisms is known to be an essential mechanism for survival and growth. Metal ions attach to enzymes in the bacteria and give these structure for incorporation into the growing organism and some earlier research seemed to suggest a connection between zinc sequestration, manganese and Lyme disease bacteria but this is the first time that connection has been fully elucidated.
Oceanographer Provides Answers to Lyme Disease Riddle
After many years of confusion due to the difficulties inherent in this kind of research, scientists have now identified the metals in these proteins in Borrelia. This was done courtesy of collaboration between a marine chemist and researchers at JHU and the UofT, using liquid chromatography mass spectometry to analyse separate proteins in the individual bacteria and then inductively coupled plasma mass spectometry to measure metals down to their parts per trillion. Through such painstaking research it has been uncovered that Lyme disease bacteria favour manganese over iron, but what does that mean for patients infected with Lyme disease?
SOD and Lyme Disease
It turns out that the researchers discovered an amino peptidase enzyme and a fairly well known enzyme, superoxide dismutase (and antioxidant enzyme) that involve manganese, rather than iron, in the biochemical processes of Borrelia. The bacteria use the superoxide dismutase to neutralize superoxide radicals thrown by the immune system at the pathogen to try to destroy it. What this means it that there may be a new target for drug development that acts inside the cell to halt the bacterium’s growth whilst not affecting any enzymes the patient relies on themselves.
New Target for Lyme Disease Treatment
These manganese-dependent enzymes may offer such a target but the researchers are not limiting themselves to just one. Instead, they will be continuing to map out the metal-dependent enzymes used by Lyme disease bacteria in order to catalogue those dependent on metal ions, offering even greater numbers of options for drug developers to beat Lyme disease in the future. What this might mean for Lyme disease patients in the meantime is to not worry too much about avoiding sources of iron during active infection but to consider instead the levels of manganese that might be present in their daily multivitamin and mineral supplement.
J. D. Aguirre, H. M. Clark, M. McIlvin, C. Vazquez, S. L. Palmere, D. Grab, J. Seshu, P. J. Hart, M. Saito, V. C. Culotta. A Manganese-Rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi. Journal of Biological Chemistry, 2013.
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