Topic: Mycoplasma toxin discovery could lead to therapy for asthma, other conditions
Mathias
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Member # 5298
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New research published in June of this year.
The mycoplasmas are the smallest of all bacteria, almost inscrutable in their ways of operating. Microbe hunters seek the answers to many questions about them. What are mycoplasmas doing to our bodies? How do they persist in our tissues? Can we develop vaccines against them? For more than three decades, Joel B. Baseman, Ph.D., professor and chair of the department of microbiology and immunology at the Health Science Center, has looked at countless microscope slides and bacterial cultures to answer the questions.
This spring, Dr. Baseman, senior author, and his prot�g�, T.R. Kannan, Ph.D., lead author, reported what Dr. Baseman says is the most exciting discovery ever to come out of his laboratory: identification of the first toxin produced by a disease-causing mycoplasma. ``This discovery is arguably the most important in the field since the discovery of the classical toxins of diphtheria and pertussis decades ago,'' Dr. Baseman said.
The toxin is produced by the respiratory pathogen Mycoplasma pneumoniae. ``This mycoplasma species is incredibly common, and is spread by sneezing, coughing, talking and touching hands to nose,'' said Dr. Kannan, instructor of microbiology and immunology.
Half of all people are infected with it. By persisting in the lungs and flaring up from time to time, it is thought to be responsible for millions of cases of child and adult asthma. ``Even cases of the sniffles that we call colds may actually be manifestations of infection with this bacterium,'' Dr. Kannan said. ``Studies of its mechanisms of operation could improve diagnosis and treatment of a wide range of human diseases, including acute and chronic airway diseases, but also diseases affecting other parts of the body, such as the heart, central nervous system, skin, joints, kidney and liver, that appear to be targets of M. pneumoniae and its toxin, as well.''
The historic paper was published in Proceedings of the National Academy of Sciences, and was so well received by the world's scientists that it was included in the Research Highlights section of Nature. Harvard Medical School's R. John Collier, Ph.D., one of the leading toxin experts in the world, highlighted the paper as a must read for the Faculty of 1000 Biology, composed of elite scientists around the world.
M. pneumoniae accomplishes its ill effects by escaping drug therapy, by having the unique ability to persist in its host for long periods, and by producing the newly discovered toxin, the researchers said. ``It can go deep inside cells to escape therapy, becoming quiet and dormant to escape detection,'' Dr. Kannan said. ``This bacterium is so small that it cannot live outside the host, so it persists in order to maintain its relationship with the host.''
It is the first microbial toxin found to date that carries out dual cell-disrupting functions, called ribosylation and vacuolation, rather than one, Dr. Baseman said.
Ribosylation involves enzymatically cutting an essential cell molecule called NAD into two pieces. One of the pieces is attached to specific proteins by the toxin, resulting in protein dysfunction or inactivation and ultimately to cell death. Vacuolation is disruption of cell membrane structure and integrity, also leading to cell death.
Infections caused by the diphtheria and pertussis bacteria initiate ribosylation through the action of their respective toxins. Helicobacter toxin, which causes stomach and intestinal ulcers, initiates vacuolation. But M. pneumoniae is more versatile than that.
``M. pneumoniae is involved in disease paths throughout the body,'' Dr. Baseman said. ``We have looked for a toxin that can explain it all. Now we've got it. We have uncovered a 50-year-old mystery in bacterial pathogenesis.''
-------------------- Mathias Posts: 1250 | From New Jersey | Registered: Feb 2004
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Marnie
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Member # 773
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Similarity between Bb and mycoplasma:
Re: Bb...
``Their lipid components are unusual in that they
*** include cholesterol;
this substance has been found in only one other bacterial genus, Mycoplasma.
The nutritional requirements of the borreliae are more complex than those of leptospires. Glucose, amino acids, long-chain fatty acids, N-acetylglucosamine, and several vitamins are some of their required organic nutrients.
The borreliae are microaerophilic organisms. Borrelia hermsii has a generation time of 12 hours when cultivated in artificial media at 35�C compared with only 6 to 10 hours in the mouse.''
Curious that d-ribose...a glyconutrient is needed to make RNA...to convert to DNA...RNA is "unstable"
Geeeze...I wish I was a biochemist!
Bb and mycoplasm are the only 2 pathogens that do not have a LPS layer/membrane.
reverse transcriptase = An enzyme, requiring a DNA primer, that catalyzes the synthesis of a DNA strand from an RNA template. An enzyme that can use RNA as a template to synthesize DNA.
You might also want to link him to the following...
Look to be related...ribosylation and riboswitches...perhaps. Bb does contain (genetic research indicates) a Mg transporter protein.
``Riboswitches are a recently discovered class of gene expression regulators. They control gene expression through a segment of messenger RNA (mRNA)--the copy of a gene that is used to produce a protein--that interacts with a target molecule to regulate its own translation into protein.
Usually, the protein regulated by the riboswitch is part of the cellular machinery that regulates the levels of the target molecule.
When the switch detects that magnesium has dropped to too low a level, it can boost the translation of the RNA--meaning the cell produces more of the transporter protein, thereby correcting the magnesium deficiency.
Every energy-producing reaction in the cell depends on magnesium as an accompanying cofactor for the cell's main energy molecule, ATP. Magnesium is also essential for the stability of the cell's membranes and its protein-producing ribosomes.
Groisman noted. ``And they will likely be involved in similar sensing mechanisms.''
The proteins that transport magnesium into the cell--MgtA and MgtB--had been know for decades, Groisman said.
And he and his colleagues discovered a decade ago that a regulatory system they called PhoP/PhoQ switches the genes for the transporters on or off in response to changing magnesium levels.
``But before this work, it wasn't suspected at all that a riboswitch might sense magnesium levels in the cell,'' Groisman said.
``Although there was no reason to think there should be any additional regulation, we found evidence that there was, indeed, an independent magnesium sensor in the cell,'' he said.
One piece of evidence came in the form of a mutation in the Salmonella bacterium that the researchers studied. That mutation in the PhoQ protein should have rendered the cell unable to respond to low magnesium levels, but the transporter genes remained sensitive to fluctuations in the mineral, said Groisman.
So, the researchers decided to analyze in detail how the mRNA molecule for mgtA responded to magnesium, in hopes of discovering a basis for magnesium-sensing. To do so, they dissected the function of the components of the Salmonella bacterium's mRNA for mgtA by systematically altering those parts' function and observing the results.
Their studies revealed that a region at one end of the mRNA molecule--which is not translated into the MgtA protein--responded to levels of magnesium.
A specific structure in this untranslated region, they showed, adopted different shapes depending on the level of magnesium in the bacterium.
Their studies revealed that a region at one end of the mRNA molecule--which is not translated into the MgtA protein--responded to levels of magnesium.
A specific structure in this untranslated region, they showed, adopted different shapes depending on the level of magnesium in the bacterium.
``Although we still have much work to do to understand the system, our analysis indicates that, in response to different magnesium levels, these different structures either allow or prevent the full-length messenger RNA from being translated,'' said Groisman.
He noted that the sequence of the untranslated region is conserved across many organisms, which indicates that it has a critical regulatory role.
In further studies, Groisman and his colleagues hope to understand in greater structural detail how the riboswitch senses magnesium levels--pinpointing the particular part of the molecule influenced by magnesium.
Also, he said, the researchers will seek to understand how this magnesium sensor applies the brakes on translation of the mRNA into the magnesium transporter protein, MgtA.
Researchers from Children's Hospital and Regional Medical Center in Seattle and the University of Washington School of Medicine have identified a magnesium transport protein that is essential to cell replication.
The research results, published today in the July 25 issue of Cell, show that tumor cells containing the protein divide rapidly, while cells lacking the protein become magnesium deficient and unable to divide.
"Our results indicated that this magnesium transport protein has a role in mediating magnesium uptake into cells. Special properties of the protein include forming a pore in the cell wall for magnesium to move through and an enzyme, which modifies other cellular proteins," said Dr. Scharenberg.
If this transporter protein is too abundant (in mice so far) it looks like there is an increased Mg and Ca LOSS via the urine:
``Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance.''
Kidney International (2006) 69, 1786-1791. doi:10.1038/sj.ki.5000344; published online 22 March 2006
(But we know that insulin shock doesn't work to cure lyme. It was tried by a doctor in Atlanta.)
Guessing...linked to bicarbonate (OH) loss -> acidosis as the pathogen converts RNA->DNA.
Metabolic acidosis (blood CO2 levels low)= respiratory alkalosis.
posted
Wow! This was way too scientific for my little brain to follow. (I really wish I could understand it, though). My kids have lyme, but my other non-lyme doc diagnosed mycoplasma pneumonia in me and my other daughter. What caught my eye is the reference to D-Ribose. He keeps pushing this product, and I couldn't really find anything to support taking it. Would this actually help with a mycoplasma infection? Thank you!
Posts: 2 | From San Diego | Registered: Jul 2006
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posted
What is the ref. to Bicarbonate and Acidosis mentioned ? My doc said my citrate is the lowest he has ever seen. Also low Renin and Aldosterone; Pos. western blot, (10 bands)
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Citrates convert to bicarbonates.
Looks to me like these diseases = bicarbonate loss = metabolic acidosis which = respiratory alkalosis.
d ribose, a teeny tiny form of sugar (called a glyconutrient) apparently is needed to make RNA.
We actually make RNA all the time. It converts to DNA.
Another nutrient Bb is taking from us (!), likely to make it's OWN DNA.
Would I take d ribose? In a heartbeat....along with many other nutrients.
IMO..the MOST CRITICAL nutrients/supps. are: Probiotics, Mg citrate, lecithin (for the phosphorus and choline), B vitamins (to support, since the "good guys" are taking a hit), and vitamin E. A good daily vit-mineral supp. to fill in the rest.
Probiotics...the beneficial bacteria make B vitamins for us...more than we consume. They bind zinc.
Mg because it locks onto ATP to power the cells...and for many, many, many other reasons!
Citrate because it converts to bicarbs.
phosphorous...ATP is made from phosphorus/phosphate choline...low levels = DNA damage
(the last 2 = lecithin which is a fat emulsifier...to "thin" the cholesterol, to prevent a "fatty liver")
B vitamins...to support what our beneficial bacteria make
Vitamin E. Powerful antioxidant to help protect the organs from ethanol.
The daily vitamin-mineral complex to fill in the gaps. Hopefully, one would also be following a very good diet and avoiding all junk foods and beverages.
Now...of course, I would supp. a LOT more...highly chosen, but it looks like the above are the absolute most critical nutrients. I am trying hard to make this "affordable" because I am well aware of the tremendous financial hit having this disease takes.
The goal should be...IMO...to keep the nutrient levels up for as many hours a day as possible. SMALL doses more often...NOT just a large dose one or two times a day.
This is why many docs want you to take SR...slow release or ER...extended release...
It's too bad there is not a computer program where persons could check off all the foods and beverages they like and then the program would spit out a menu plan that is nutritionally balanced based on their individual preferences.
I do think we chose foods that our body needs...somehow the body is "telling" us what it needs to stay in balance.
I know several kids with learning problems that absolutely crave cereal...or should I say...crave the B vitamins? And they pour on the sugar because glycogen is brain fuel.
Listen to what your body is telling you.
Now...hand over that chocolate ;-)
[ 20. July 2006, 07:50 AM: Message edited by: Marnie ]
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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TerryK
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Al, My aldosterone and renin are low. Part of the orthostatic hypotension and possibly the low blood volume problem. I've never had my citrate measured. I have IgeneX positive IgM and IgG WB. Terry
Posts: 6286 | From Oregon | Registered: Jan 2006
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