BIOLOGICAL SCIENCES / MICROBIOLOGY Borrelia burgdorferi intercepts host hormonal signals to regulate expression of outer surface protein A
Mark R. Scheckelhoff*, Sam R. Telford, Mary Wesley*, and Linden T. Hu*,
*Division of Geographic Medicine and Infectious Diseases, Tupper Research Institute, Tufts-New England Medical Center, Boston, MA 02111; and Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA 01536
Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved March 18, 2007 (received for review August 23, 2006)
The Borrelia burgdorferi infectious cycle requires that the organism adapt to vast differences in environmental conditions found in its tick and mammalian hosts.
Previous studies have shown that B. burgdorferi accomplishes this accomodation in part by regulating expression of its surface proteins. Outer surface protein A (OspA) is a borrelial protein important in colonization of the tick midgut.
OspA is up-regulated when the organism is in its tick host and down-regulated when it is in a mammalian host.
However, little is known about how it is up-regulated again in a mammalian host in preparation for entry into a feeding tick.
Here, we report that the host neuroendocrine stress hormones, epinephrine and norepinephrine, are specifically bound by B. burgdorferi and result in increased expression of OspA.
This recognition is specific and blocked by competitive inhibitors of human adrenergic receptors.
To determine whether recognition of catecholamines, which are likely to be present at the site of a tick bite, may play a role in preparing the organism for reentry into a tick from a mammalian host, we administered a -adrenergic blocker, propranolol, to infected mice.
Propranolol significantly reduced uptake of B. burgdorferi by feeding ticks and decreased expression of OspA in B. burgdorferi recovered from ticks that fed on propranolol-treated mice.
Our studies suggest that B. burgdorferi may co-opt host neuroendocrine signals to inform the organism of local changes that predict the presence of its next host and allow it to prepare for transition to a new environment.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
tailz
Unregistered
posted
I actually was placed on this medication before they knew I had Lyme, but I only took a couple of pills at best - maybe even just one - I forget.
As soon as I took this pill, within minutes, my heart rate slowed dramatically, and it was kind of scary. I thought my heart was going to stop, and I never took one again.
Though I think it's possible that this drug might help those who only have Lyme, they also need to factor in coinfections that might respond less favorably to the addition of this medication.
IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Wow, thanks for the insight. That's pretty scary.
Were you on any ABX at the time? Perhaps it just caused them to take some other action, if there was nothing present to kill them off.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
Foggy
Frequent Contributor (1K+ posts)
Member # 1584
posted
Prior to my Lyme dx, I used to take it for anxiety & it was very helpful. Made me mellow & less twitchy.
NEMC is NOT LL!
Posts: 2451 | From Lyme Central | Registered: Aug 2001
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
That's very interesting. I wonder why such a difference in response.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
posted
Propranolol is given to lower blood pressure quickly, within half an hour. It also has off label uses, such as social anxiety and I think it also prevents blushing. I think it's a beta blocker.
Instead of taking a whole one try taking a half. I have this med. because my blood pressure was spiking. I never took a whole one at once. Try a half or even a quarter.
-------------------- sunnymalibu Posts: 192 | From california | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
I guess that lets me out. The Babesia keeps dropping my BP.
Thanks Sunny.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
posted
AliG-you can take Proamatine to raise your blood pressure. It's a med that is given for low blood pressure.
Several weeks ago my blood pressure was about 90/60 and I felt like a wet noodle. Could hardly move. I started using heparin and my blood pressure is back to normal.
You can read about heparin and infections at the www.hemex.com site.
I used to live in Summit, N.J. and moved to Los Angeles. Don't miss the weather there at all!
Best wishes!
-------------------- sunnymalibu Posts: 192 | From california | Registered: Jul 2006
| IP: Logged |
posted
Very low dose propananol really helps me because I can get quite severe adrenaline attacks often related to the way my body reacts to blood sugar I believe but it is also so helpful when any really stressful situation arises like going to the dentist for treatment.
I always feel better about 3/4 hour after taking 10mg, sometimes 15mg but I only every took 20mg when I went through a period of high bp. Now its back to normal and I only take the betablocker on an as needed basis and use a very low dose.
treepatrol
Honored Contributor (10K+ posts)
Member # 4117
posted
A is what is in the tick as soon as it enters a human or warm blooded it expresses B
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
These are exactly the avenues we need to explore to incapacitate Bb. It appears that Bb needs these outer surface lipoproteins(Osps) to simulate inflammation which helps Bb evade our immune system. This article suggests using propranolol, an alpha blocker to control the inflammation.
The Marshall Protocol uses a beta blocker- Benicar to minimize inflammation. So this concept is certainly Key.
Thanks for sharing this with us. Ernie
Posts: 546 | From Cascadia subduction zone | Registered: Mar 2002
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Thanks Sunny,
I'm familiar with that noodle feeling.
I generally load up on some high sodium liquids like chicken broth, eat some black licorice (the real stuff) and drink some good strong coffee on the occasions when my BP drops REALLY low.
I have also used hot cocoa on the rare occasions when it has gone way up.
I had read about heparin, a while back. I thought it sounded really interesting, especially since my blood tends to get sludgy. Thanks for the link.
I have this strange need to keep from medically treating the individual symptoms. (Unless they would land me in the hospital . I somehow believe that the nature of the symptoms & their cycles might somehow give me a better understanding of what these critters are doing in there.
I don't want to cover up anything that might help me get rid of them.
You may not miss the weather, but I'll bet you miss the pizza. We used to have to ship Taylor Ham (pork roll) to family, while they were living there.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Lil,
You're welcome & Thank you.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Thanks Tree,
Would they be more succeptible to ABX while in the process of changing their Osps from A to B or B to A?
Would it help to rid them if we can make them change their defenses, while attacking them?
Maybe if we can make them go back & forth repeatedly, they'll drop dead from exhaustion. (OK now that's REALLY an odd thought, but wouldn't it be fun to just "tick" them off for a change? )
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Glad you liked it Ernie!
I looked up Benicar. It's actually an Angiotensin Receptor Blocker (ARB). I found a great article on ARBs possibly modulating the immune system (Marshall)& have been trying to figure out all day why my bleeping computer won't let me copy & paste info (among other things).
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
1Autoimmunity Research Foundation, Thousand Oaks, California 91360, USA 2Black Hawk College, Moline, Illinois 61443, USA 3Los Robles Regional Medical Centre, Thousand Oaks, California 91360, USA
Theoretical Biology and Medical Modelling 2006, 3:1 doi:10.1186/1742-4682-3-1
Published 10 January 2006
Abstract
Background
There have been indications that common Angiotensin Receptor Blockers (ARBs) may be exerting anti-inflammatory actions by directly modulating the immune system.
We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation.
We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D.
This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone) and the Parathyroid Hormone (PTH).
Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b), which recruits monocytes to the site of inflammatory immune challenge.
Results
Telmisartan was predicted to strongly antagonize (Ki≈0.04nmol) the VDR.
The ARBs Olmesartan, Irbesartan and Valsartan (Ki≈10 nmol) are likely to be useful VDR antagonists at typical in-vivo concentrations.
Candesartan (Ki≈30 nmol) and Losartan (Ki≈70 nmol) may also usefully inhibit the VDR.
Telmisartan is a strong modulator of PPARgamma (Ki≈0.3 nmol), while Losartan (Ki≈3 nmol), Irbesartan (Ki≈6 nmol), Olmesartan and Valsartan (Ki≈12 nmol) also seem likely to have significant PPAR modulatory activity.
Olmesartan andIrbesartan (Ki≈9 nmol) additionally act as antagonists of a theoretical modelof CCR2b.
Initial validation of this CCR2b model was performed, and a proposed model for the AngiotensinII Type1 receptor (AT2R1) has been presented.
Conclusion
Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design.
ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b.
However, this study also found evidence that ARBs modulate the activation of two key nuclear receptors-VDR and PPARgamma.
If our simulations are confirmed by experiment, it is possible that ARBs may become useful as potent anti-inflammatory agents, in addition to their current indication as cardiovascular drugs.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
sometimesdilly
Frequent Contributor (1K+ posts)
Member # 9982
posted
dear dear ali-
excuse this interuption of the regularly scheduled programming and thread- i have no idea what you are talking about here, but wanted to send you a great big hug and thank you. hope things are looking up for you... dilly
Posts: 2507 | From lost in the maze | Registered: Aug 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
You can interrupt me anytime, pal! I'll always break for hugs!
Glad to see you here! I've been worrying about you something fierce! I hope all is well. I'll have to run over to general to see if you've posted an update, so I don't make you tire your fingers.
BRB guys, please excuse me for a minute.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Back again....
I believe both propranolol & Benicar lower BP. So maybe add high-sodium diet?
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
posted
This is interesting to me as well. I have suffered from anxiety/panic disorder for three years. I just stopped taking atenolol and celexa a few months ago cause I was feeling better.
Then I got the tick bite in June and have been sick ever since. Being sick and worrying has really kicked up my anxiety, lots of palpitations, and racing pulse.
My doctor suggested starting the Celexa and Atenolol again since my anxiety has kicked up. I started them again last night. Talk about being tired today. The tiredness is normal when you start taking a beta blocker and an anti-depressant. I certainly hope they help me out in addition to the doxycycline I am currently taking.
-------------------- Just looking for answers. i appreciate all the help everyone on the board have provided Posts: 34 | From Missouri | Registered: Jul 2007
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
I'm not sure why, but this sounded interesting.
This article has been cited by other articles in PMC.
AbstractThe effect of atenolol, propranolol, trifluoperazine, and caffeine on the occurrence of meiotic diploid and disomic products in Saccharomyces cerevisiae was investigated.
We demonstrated that atenolol, propranolol, and trifluoperazine reduce the occurrence of meiotic diploid products and that propranolol also slightly decreases the spontaneous frequency of disomics.
On the other hand, caffeine appears to be a powerful inducer of diploid meiotic products, but also shows a lesser effect on disomic induction.
Since spontaneous or caffeine-induced diploids arise from a failure of the second meiotic division, it appears that the target of these drugs is at the beginning of the second meiotic division.
The only common effect of trifluoperazine and propranolol, mainly investigated in mammals, was an inhibition of calmodulin activity via direct interaction.
We tend, therefore, to believe that calmodulin activity must be a crucial point for the second meiotic division to begin.
The increased induction of diploids, due to caffeine, may be interpreted as a consequence of an increased cyclic AMP level.
It would seem that they effect the cell division of yeasts, with caffeine having the opposite effect of the others?
I wonder if they also effect bacteria(Lyme) and/or protozoa(Babesia). ??
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
This is great Roger!
Please try to let us know how you're progressing. If you notice a difference, having added them. How long have you been on the Doxy alone?
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
| IP: Logged |
The Lyme Disease Network is a non-profit organization funded by individual donations. If you would like to support the Network and the LymeNet system of Web services, please send your donations to:
The
Lyme Disease Network of New Jersey 907 Pebble Creek Court,
Pennington,
NJ08534USA http://www.lymenet.org/
UBBFriend: Email this page to someone!
![[Eek!]](eek.gif)
![[confused]](graemlins/confused.gif)
![[Roll Eyes]](rolleyes.gif)
![[hi]](graemlins/hi.gif)
![[loco]](graemlins/loco.gif)
![[Razz]](tongue.gif)
We used to have to ship Taylor Ham (pork roll) to family, while they were living there.![[Smile]](smile.gif)
![[woohoo]](graemlins/woohoo.gif)
![[lol]](graemlins/lol.gif)
(OK now that's REALLY an odd thought, but wouldn't it be fun to just "tick" them off for a change? ![[Big Grin]](biggrin.gif)
)![[Mad]](mad.gif)
.![[kiss]](graemlins/kissing.gif)
Printer-friendly view of this topic