ScienceDaily (Feb. 9, 2009) -- Researchers at UT Southwestern Medical Center have identified a protein that may help give Lyme disease its bite.
The findings suggest that the bacterial protein, which aids in transporting the metal manganese, is essential for the bacterium that causes Lyme disease to become virulent.
"We believe our findings provide a foundation for further defining metal homeostasis in this human pathogen and may lead to new strategies for thwarting Lyme disease," said Dr. Michael Norgard, chairman of microbiology at UT Southwestern and senior author of a study now online and in an upcoming issue of the Proceedings of the National Academy of Sciences.
Lyme disease, discovered in 1977, is the most prevalent tick-borne infection in the U.S. Borrelia burgdorfei, the bacterium that causes Lyme disease, lives in infected mammals and in the midgut of ticks.
When an infected tick bites an animal or a human, the bacteria are transmitted to the new host.
Infection causes fever, malaise, fatigue, headache, muscle and joint aches, and a characteristic "bull's-eye" rash that surrounds the site of infection.
To establish infection, however, the bacterium also must acquire a number of essential nutrients, including metals like manganese from its mammalian and tick hosts.
Until now, no metal transporter responsible for this acquisition had been identified in this bacterium.
In the current study, microbiologists examined whether bacteria genetically engineered to lack this manganese transporter, called BmtA, transmitted Lyme disease to ticks and mice.
The bacterium lacking the transporter, Dr. Norgard said, grows a bit more slowly in the test tube but is not dramatically different from the normal version.
"When you try to grow it in a mouse, however, it can't grow," he said.
"The fact that the bacterium without this particular manganese transporter can't grow in a mouse raises important questions about what aspects of physiology and metabolism contribute to the pathogenicity of the organism."
Lead author Dr. Zhiming Ouyang, postdoctoral researcher in microbiology at UT Southwestern, said another newly discovered characteristic about the bacterium that causes Lyme disease is that it doesn't seem to require iron to function, something most other pathogens need to survive.
"Out of the thousands of bacteria known, the Lyme disease agent and only one or two other bacterial species do not require iron for growth," Dr. Ouyang said.
"That raises the question as to what other metal co-factors the Lyme disease bacterium depends on to carry out the work that iron does for all these other biological systems.
Our research suggests that manganese is a really important one."
The next step is to understand the exact mechanism of how manganese functions in the organism.
"I really think that there's also something to the notion that manganese may regulate the expression of other virulence factors," Dr. Norgard said.
"It could be that manganese has more of an indirect effect, but more research is needed to determine what must happen for Borrelia burgdorfei to become virulent."
Researchers from Indiana University School of Medicine collaborated on the study.
The research was funded by the National Institute of Allergy and Infectious Diseases.
Adapted from materials provided by UT Southwestern Medical Center.
My apologies if this has already been discussed... Posts: 24 | From co | Registered: Sep 2007
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bettyg
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lulu, i haven't seen it, but i'm sure that gigi, oxygen, etc. will read it over and give you input.
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oxygenbabe
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I will try to find out more about this. Along with the interesting blog info I posted a few days ago (a blog called Spirochetes Unwound) we may be getting somewhere. BB is virulent because it's invasive. It's invasive because it moves thru tissue (I wonder if the manganese helps it power its "motor") and into cells--therefore it's invasive because of its ability to attach and penetrate. What does it attach to and what chemicals does it release in order to penetrate?
If you go find my posting--there are videos on that blog that are kind of astounding. They were able to track the borrelia by making them fluoresce and one of the videos shows this dang little borrelia that wouldn't give up. It kept butting against the epithelium and couldn't get through and it just kept trying until it did. I would assume each time it released some kind of chemical.
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oxygenbabe
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Addendum, here's some info on the principal investigator:
Michael V. Norgard, Ph.D. Professor and Chair of Microbiology
Syphilis and Lyme disease are chronic, complex infections caused by the spirochetal bacteria Treponema pallidum and Borrelia burgdorferi, respectively. While syphilis and Lyme disease are transmitted differently (i.e., sexually or through the bite of a tick), they share many common features. These include penetration of the organism through skin, dissemination via the bloodstream, and immune evasion leading to chronic disease. Acute and chronic inflammatory responses are associated with both diseases.
Little is known about the virulence factors or immune responses operative in the immunopathogenesis of syphilis and Lyme disease. The paucity of information about syphilis stems primarily from the inability to cultivate T. pallidum in vitro. Although B. burgdorferi can be cultivated in vitro, its complex life cycle (i.e., in ticks and in mammals) has hampered understanding its virulence traits. Also, identification of the proinflammatory molecules of both organisms may hold the keys to clarifying virulence factors, to understanding the invasive and chronic natures of T. pallidum and B. burgdorferi, to explaining spirochetal immunopathogenesis, and to understanding potential spirochetal control through vaccine development.
A major goal of our laboratory program is to identify, characterize, and isolate spirochetal membrane proteins of biological significance to the immunopathogenesis processes of syphilis and Lyme disease. We have discovered that the major integral membrane proteins of both T. pallidum and B. burgdorferi are lipoproteins (proteolipids). Bacterial lipoproteins are known to exhibit potent biological activities, such as the ability to activate B cells, macrophages, and other immune effector cells. In syphilis, this has important implications not only to immunopathogenesis, but also for cellular events that likely contribute to HIV transmission (syphilis is an important cofactor for HIV transmission). In the case of B. burgdorferi, certain lipoproteins appear to be upregulated when the spirochete resides in ticks, whereas others appear to be upregulated as the organism prepares itself to invade mammalian tissues. We recently discovered an alternative sigma factor (RpoN-RpoS) regulatory pathway that controls the expression of key lipoprotein virulence factors in B. burgdoreri. The complex gene regulation systems governing such differential antigen expression are critical for sustaining B. burgdorferi in its very different niches of ticks and mammals. Elucidation of such systems will reveal much about the parasitic strategies of this important human pathogen.
Contemporary approaches in molecular biology, structural biology, immunology, and cell biology are being used for the identification, isolation, and characterization of membrane proteins and lipoproteins of T. pallidum and B. burgdorferi of potential relevance to immunopathogenesis and vaccine development. Structural and functional studies of selected integral membrane proteins are underway to understand how the peculiar membrane biology of T. pallidum and B. burgdorferi contributes to the host-parasite relationship, tissue dissemination, and immune evasion. Given that both T. pallidum and B. burgdorferi have dual membrane systems that differ markedly from those of Gram-negative bacteria, research emphasis also is being placed on discerning the membrane topologies of key integral membrane proteins/lipoproteins. Lastly, various molecular methodologies are being applied to improve the diagnosis of syphilis, congenital syphilis, and Lyme disease.
Finally, our lab recently has begun work to support the national biodefense initiative. Francisella tularensis is a Class A bacterial biothreat that is easily weaponized and was previously the focus of much biowarfare research in the former Soviet Union. Infection with F. tularensis, also known as rabbit fever, is a zoonotic infection of small wild animals, but causes a serious, life-threatening infection when humans are inadvertently exposed. Along with other faculty in the Department of Microbiology, a large multi-component program project is underway to elucidate factors that may contribute to the virulence of F. tularensis infection. This work is being conducted under strict biological safety level-3 containment.
News Publications:
UT Southwestern researchers receive $15.1 million in federal grants to study biothreats
UT Southwestern researchers uncover key to survival ability of bacterium that causes Lyme disease
Selected Publications:
Bouis, D., T.G. Popova, A. Takashima, and M.V. Norgard. 2001. Dendritic cells phagocytose and are activated by Treponema pallidum. Infection and Immunity 69:518-528.
H�bner, A., X. Yang, D.M. Nolen, T.G. Popova, F.C. Cabello, and M.V. Norgard. 2001. Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc.Natl.Acad.Sci.U.S.A. 98:12724-12729.
Revel, A.T., A.M. Talaat, and M.V. Norgard. 2002. DNA microarray analysis of differential gene expression in Borrelia burgdorferi, the Lyme disease spirochete. Proc.Natl.Acad.Sci.U.S.A. 99:1562-1567.
Deka, R.K., M. Machius, M.V. Norgard, and D.R. Tomchick. 2002. Crystal structure of the 47-kilodalton lipoprotein of Treponema pallidum reveals a novel penicillin-binding protein. Journal of Biological Chemistry 277:41857-41864.
Yang, X.F., S.M. Alani, and M.V. Norgard. 2003. The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi. Proc.Natl.Acad.Sci.U.S.A. 100:11001-11006.
Yang, X.F., U. Pal, S.M. Alani, E. Fikrig, and M.V. Norgard. 2004. Essential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete. Journal of Experimental Medicine 119:641-648.
Revel, A.T., J.S. Blevins, C. Almazan, L. Neil, K.M. Kocan, J. de la Fuente, K.E. Hagman, and M.V. Norgard. 2005. BptA (bbe16) is essential for the persistence of the Lyme disease spirochete, Borrelia burgdorferi, in its natural tick vector. Proc.Natl.Acad.Sci.U.S.A. 102:6972-6977.
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Can someone boil this down for me? Does this mean we should eat less iron-rich foods? Manganese-rich foods? Which foods are they? I am a little concerned about this as I've been trying to to bump up veg intake to get more vitamins.
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Hoosiers51
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IU as in Indiana University? Where does it say that? Indiana Univ. does have a school of medicine by the way.
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CD57
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Regarding bart/BLO and the OTHER TBDs: this means that Bea is onto something when she started her husband on lactoferrin.....this is an iron binding protein that would essentially help starve the other bacteria inside us....although it would help Bb.
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Keebler
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Thanks to all for the articles.
I have homework for later. Leaf blowers just arrived for the day . . . reading is shelved for now.
charlie
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....I've known several welders who have parkinson-like tremors supposedly from absorbing too much manganese while handling welding rods.
Charlie
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Dekrator48
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Thank you for posting this. It is very interesting.
-------------------- The fibromyalgia I've had for 32 years was an undiagnosed Lyme symptom.
"For I know the plans I have for you", declares the Lord, "plans to prosper you and not to harm you, plans to give you hope and a future". -Jeremiah 29:11 Posts: 6076 | From Pennsylvania, USA | Registered: Nov 2008
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Isn't it ironic, that they must focus on virulence factors of known biowarfare strains to gain insight to BB pathogenisis? Microw
-------------------- microw Posts: 129 | From Toronto, ON Canada | Registered: Feb 2008
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blaze
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And this is why I believe cell phone tower radiation is involved in the virulence of Lyme. It also would explain the greyish-white film that keeps adhering to my teeth that I figured was some metal, originally I thought it was iron...
Manganese is a gray-white metal, resembling iron. It is a hard metal and is very brittle, fusible with difficulty, but easily oxidized. Manganese metal and its common ions are paramagnetic. While manganese metal does not form a permanent magnet, it does exhibit strong magnetic properties in the presence of an external magnetic field.
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Very interesting from a microbiology standpoint, but I am more interested in findings that can most likely be applied to treatment and cure in humans. Microbiologists have crippled Bb in many different ways, and most modified bacteria lose their virulence, but that is not really helping patients that much.
You do have to admit though, Bb is one freaky organism. Fe is not needed, even for the electron transport chain apparently. A linear chromosome and 20+ linear and circular plasmids, but all combined around 1.5Mb pairs. It is hard to imagine that an obligate organism that has such a small genetic footprint could survive so well not only in mammals but ticks also.
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quote:Originally posted by CD57: this means that Bea is onto something when she started her husband on lactoferrin.....this is an iron binding protein that would essentially help starve the other bacteria inside us....although it would help Bb.
CD, what you are saying makes sense -- but aren't you making a large number of assumptions on this? Maybe not!? Read on...
As you may know, lactoferrin is in dairy products and in some probiotics like Theralac. As a single substance, it in inherently anti-bacterial. I found this (excerpt) from an eleven-year-old article, ANTIMICROBIAL FACTORS IN MILK, by Karen J. Losnedahl, Hong Wang, Mueen Aslam, Sixiang Zou, and Walter L. Hurley 08/05/1998
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LACTOFERRIN
Lactoferrin, an iron-binding glycoprotein, was first isolated from cow's milk and subsequently from human milk. Lactoferrin is present in large quantities in mammalian secretions such as milk, tears, saliva, and seminal fluid, as well as in some white blood cells. Lactoferrin is one of the minor proteins naturally occurring in cow milk at an average concentration of about 0.2 grams/liter.
In colostrum, the lactoferrin content can be as high as 0.5 to 1 grams/liter. During the dry period, lactoferrin concentration in mammary secretions from dry cows increases until about 30 days after drying off. The highest lactoferrin concentration found in cow mammary secretions is about 50 to 100 grams/liter. In human milk and colostrum, the reported concentrations of lactoferrin are 2 to 4 grams/liter and 6 to 8 grams/liter, respectively.
In its natural state, lactoferrin is only partly saturated with iron (5 to 30 percent). Lactoferrin has many proposed biological functions, including antibacterial/ anti-inflammatory activities, defense against gastro-intestinal infections, participation in local secretory immune systems in synergism with some immunoglobulins and other protective proteins, provision of an iron-binding antioxidant protein in tissues, and possibly promotion of growth of animal cells such as lymphocytes and intestinal cells. A role for milk lactoferrin in iron absorption by the intestine has long been postulated, but remains unproven.
Most micro-organisms need iron for growth and lactoferrin has the potential to inhibit the growth of bacteria, and even kill them by depriving them of iron. The effectiveness of the antibacterial activity of lactoferrin depends on the iron requirement of the organism, the availability of exogenous iron, and the concentration and degree of iron-saturation of lactoferrin. It has been shown that 'natural' lactoferrin is bacteriostatic against a wide range of micro-organisms, including gram-negative bacteria with high iron require- ments (coliforms, which are major mastitis pathogens), and also against some gram-positive organisms such as Staphylcoccus aureus (also a major mastitis pathogen), bacillus species, and Listeria monocytogenes. Lactic acid bacteria in the stomach and intestine have low iron requirements and are generally not affected. There is also evidence that on certain streptococcal mutants and Vibrio cholerae, lactoferrin can exert a direct, bactericidal effect that is independent of iron-deprivation.
-------------------- My biofilm film: www.whyamistillsick.com 2004 Mycoplasma Pneumonia 2006 Positive after 2 years of hell 2006-08 Marshall Protocol. Killed many bug species 2009 - Beating candida, doing better Lahey Clinic in Mass: what a racquet! Posts: 830 | From Mass. | Registered: Aug 2006
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bejoy
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Looks like that would be University of Texas.
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