Topic: Dps is critical for spirochaete persistence within ticks
Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
1: Mol Microbiol. 2007 Dec 20; [Epub ahead of print]
The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticks.
� Li X, � Pal U, � Ramamoorthi N, � Liu X, � Desrosiers DC, � Eggers CH, � Anderson JF, � Radolf JD, � Fikrig E.
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Borrelia burgdorferi survives in an enzootic cycle, and Dps proteins protect DNA against damage during starvation or oxidative stress.
The role of a Dps homologue encoded by Borrelia in spirochaete survival was assessed. Dps-deficient spirochaetes were infectious in mice via needle-inoculation at the dose of 10(5) spirochaetes.
Larval ticks successfully acquired Dps-deficient spirochaetes via a blood meal on mice. However, after extended periods within unfed nymphs, the Dps-deficient spirochaetes failed to be transmitted to a new host when nymphs fed.
Our data suggest that Dps functions to protect the spirochaetes during dormancy in unfed ticks, and in its absence, the spirochaetes become susceptible during tick feeding.
dps is differentially expressed in vivo- low in mice and high in ticks - but constitutively expressed in vitro, showing little change during growth or in response to oxidative stress.
Borrelia Dps forms a dodecameric complex capable of sequestering iron. The Dps-deficient spirochaetes showed no defect in starvation and oxidative stress assays, perhaps due to the lack of iron in spirochaetes grown in vitro.
Dps is critical for spirochaete persistence within ticks, and strategies to interfere with Dps could potentially reduce Borrelia populations in nature and thereby influence the incidence of Lyme disease.
PMID: 17181780 [PubMed - as supplied by publisher]
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"sequestering iron"
The powerful antioxidant, melatonin, which looks to be overproduced to combat the extreme oxidative stress ALSO locks onto iron...making it unavailable.
Oxygen carrying heme... Since NO and the superoxide free radical can destroy Bb...no wonder Bb doesn't like iron...and is triggering the "unavailability" of iron.
We need iron to transport oxygen. Bb can stand a little O2, but not a lot.
O3 trivalent oxygen. Powerful. Do NOT BREATHE, but...ozone SAUNAS, on the other hand may indeed be beneficial...for a few minutes on a daily basis.
When our astronauts return to earth, they have low PFK levels and are anemic.
PFK is the rate limiting enzyme for glycolysis. It is likely being utilized by Bb since we KNOW Bb is "PFK dependent".
WHICH PFK is important 'cause ONLY glucagon can INactivate both PFK 1 and PFK2 (liver). Glucagon is acidic and it "downregulates" insulin which is also acidic. However, it then triggers sugar release to keep the blood sugar level steady.
And then there's this:
"This transferrin, like those of two other insect species, has conserved iron-binding residues in the N-terminal lobe but not in the C-terminal lobe, which also has large deletions in the polypeptide chain, compared with transferrins with functional C-terminal lobes.
The hypothesis is developed that this transferrin plays a role
similar to vertebrate lactoferrin
in sequestering iron from invading organisms
and that degradation of the structure of the C-terminal lobe might be a mechanism for evading pathogens that elaborate transferrin receptors to tap sequestered iron."
Keep in mind, in lyme...flip this...it looks like Bb has a preference for the C terminal, not the N terminal.
And...
"In the 12 Nov. 2004 issue of the journal Cell, the scientists show that a key step in the process of preventing cell suicide is the induction of ferritin heavy chain (FHC), a protein that collects and hoards iron.
By sequestering iron -- which cells with suicidal tendencies need to make the harmful substances that induce death -- FHC prevents cellular suicide.
This finding suggests that drugs that modulate FHC or iron metabolism could provide a new and effective approach to anti-inflammatory therapy without the side effects, such as weakening the immune system, that come with current treatments."
Bb has a PKC inhibitor...to trigger cell death. Not good if too many cells die off too fast.
MUCH MORE INFO. ON THE ABOVE link!!!
"Mechanism of iron release from human serum C-terminal monoferric transferrin to pyrophosphate"
Pyrophosphate...now that rings a bell...;-)
"The rate constant for iron release depends linearly on chloride concentration, confirming that anion binding is mandatory for iron release, not only at pH 7.4 as has been previously reported, but also at pH 5.5.
The extent of iron release is relatively small (< 20% for 1.0 M chloride). Concentrations of > 0.2 M phosphate are required for complete iron removal, but millimolar concentrations of pyrophosphate effect complete removal." PMID: 7876832
Well...pH of 5.5 is out...what about 7.4?
"We learned that blood pH is neutral at 7.4.
We also learned that higher than 7.8 or lower than 7.0 is really bad and leads to death."
Bb: "Initial comparisons of cultures incubated at pHs 6.0, 7.0, and 8.0 yielded alterations in the expression of seven membrane proteins as determined by probing with hyperimmune rabbit serum.
Six of these membrane proteins (54, 45, 44, 43, 35, and 24 kDa) were either present in increased amounts in or solely expressed by cultures incubated at pHs 6.0 and 7.0.
The 24-kDa protein that decreased in expression at pH 8.0 was identified as outer surface protein C (OspC).
In addition, a 42-kDa membrane protein increased in amount in cultures incubated at pH 8.0.
Similar changes were observed with serum from a mouse infected by tick bite, with the recognition of two additional bands (48 and 46 kDa) unique to pHs 6.0 and 7.0.
When membrane fractions were analyzed by 2D-NEPHGE, at least 37 changes in the membrane protein profile between cells incubated at pHs 6.0, 7.0, and 8.0 were observed by immunoblotting and silver staining.
Environmental cues such as pH may prove important in the regulation of virulence determinants and factors necessary for the adaptation of B. burgdorferi to the tick or mammalian microcosm"
"CONCLUSIONS: This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. "
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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what does,'Dps' stand for? if i know what this stands for, then i have a "hook" to delve further into this aspect of persistance, and, perhaps find an "angle" of attack.
posted
Thanx, Marnie... it would seem that, interrupting this might yield some reslts...who knows...at least for now...
Tincup, Thanks for this new information. a little more digging into this might lead to a way of sabatoging the synthetic pathway(s) leading to the formation of this protein,and hopefully, to compromise this protetive effect, thereby allowing and opening to maim, if not kill borrelia, hopefully w/o maiming or killing ourselves in the process.
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Darma, try to keep your pH at the correct level...7.4 (blood pH)
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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