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» LymeNet Flash » Questions and Discussion » Medical Questions » Amphibian Skin Agent May Battle Multi-drug Resistant Bacteria

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Author Topic: Amphibian Skin Agent May Battle Multi-drug Resistant Bacteria
JRWagner
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http://www.sciencedaily.com/releases/2008/01/080122102502.htm


Hug a Frog today!

Peace, Love and Wellness,
JRW

Posts: 1414 | From Ny, Ny | Registered: Oct 2002  |  IP: Logged | Report this post to a Moderator
cottonbrain
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cool! where can i get one?
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AliG
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Very interesting info, JR. [Smile]

I've been fishing these little critters out of my pool every morning in the summer. I used to make them a little pond to live in, but now I have a dog who is something of a predator so I have to try to put them places where she can not get to them. [Roll Eyes]

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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.

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Truthfinder
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These ``antimicrobial peptides (AMPs)'' found on amphibian skin are the same things found in crocodile blood, which makes crocs very resistant to getting infections, even if they are seriously injured and even when they swim around in microbe-infested waters on a regular basis.

These AMPs may be the same things found in Western Fence Lizard blood that cure feeding ticks of Lyme Disease - I can't remember about the WF Lizard.

Unfortunately, something in live human blood `neutralizes' these AMPs before they can do any good.
[shake]

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Tracy
.... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�.

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AliG
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Oh POOP!

Thanks a lot Tracy! [Frown]

It was a nice hope while it lasted. [Roll Eyes]

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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 | Report this post to a Moderator
stormton
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But wait. They found a way to attach fluorine to these amp molecules which makes them last in the body many times longer. The idea came from teflon. Frog skin amp plus teflon equals a better antibiotic. This stuff seems promising but might take a long time before anyone is allowed to ingest them.
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AliG
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Thanks for possibly renewed hope, Stormton! [Smile]

Was that something I missed in the article or was there a study somewhere that I haven't seen as of yet?

[confused]

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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 | Report this post to a Moderator
JRWagner
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WOW...a new AMP molecule zipped up with Teflon?

Just slips righ on down...no water needed?!!

Ali...sounds like you have a Frog Monster in your midst...a POOL??? What's a pool? Water? What, you have WATER??? Jeesh, I don't gots no water...In fact, I have to run after my water...
(running water...)

Froggies make great living shawls...didn't you ever see these? Makes one want to croak....

I had a great pond when I was a kid (still am, thank you)where one could catch Bullfrogs, Leopard frogs and Turtles. PLUS...all sizes of Tadpoles...we never hurt them...my Mother went NUTS when I brought them home...something about dropping me off in the city with no money...

I am sure the men and women of science will find a way to make this work inside our bodies...perhaps in a new Ice Cream...or CHOCOLATE!!! Mango?

Peace, Love and Wellness,
JRW

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treepatrol
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quote:
Originally posted by JRWagner:
http://www.sciencedaily.com/releases/2008/01/080122102502.htm


Hug a Frog today!

Peace, Love and Wellness,
JRW

Dont lick em [Big Grin] JR

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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.

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h8lyme
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I don't think I want to be one of the first on this med. Sounds a bit scary, alligator or frogs blood...
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AliG
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JR, no comment. [Roll Eyes]



I'm sorry this is just too funny. [lol]

quote:
originally posted by treepatrol:

Dont lick em [Big Grin] JR

Best be careful, you might end up with warts on your tongue. [Razz]

LOL

--------------------
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.

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Truthfinder
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Yeah, or it might turn into a Prince or something.... which could end up being a lot worse than warts.

Fluorine? Interesting. I hadn't heard about that.

I remember all the excitement over shark cartilage and the medical cancer-preventative implications from that, but nothing ever came of it in the scientific world.

Maybe they can figure this frog puzzle out.....

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Tracy
.... Prayers for the Lyme Community - every day at 6 p.m. Pacific Time and 9 p.m. Eastern Time � just take a few moments to say a prayer wherever you are�.

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AliG
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University of Michigan News Service, 412 Maynard, Ann Arbor, MI 48109, [email protected]


Aug. 20, 2007
Frog plus frying pan equals better antibiotic

ANN ARBOR, Mich.--What do you get when you cross a frog with a frying pan? Possibly a solution to the problem of drug-resistant bugs, research at the University of Michigan suggests.

By creating "Teflon" versions of natural antibiotics found in frog skin, a research team led by biological chemist E. Neil Marsh has made the potential drugs better at thwarting bacterial defenses, an improvement that could enhance their effectiveness.

Marsh will discuss the work Aug. 20 at the 234th national meeting of the American Chemical Society in Boston. Marsh and collaborators work with compounds called antimicrobial peptides (AMPs), which are produced by virtually all animals, from insects to frogs to humans.

AMPs are the immune system's early line of defense, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces.

They're copiously produced in injured or infected frog skin, for instance, and the linings of the human respiratory and gastrointestinal tracts also crank out the short proteins in response to invading pathogens.

In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications.

Scientists have been interested in exploiting these natural antibiotics since their discovery in the 1980s, but they haven't been able to overcome some limitations.

In particular, AMPs are easily broken down by protein-degrading enzymes (proteases) that are secreted by bacteria and are also naturally present in the body.

Increasing the concentration of AMPs in an effort to get around that problem can cause toxic side effects, such as the destruction of red blood cells--those critical carriers of oxygen in the bloodstream.

That seems to happen because sticky parts of the AMP molecule interact with the cell membrane in a harmful way.

Marsh had the idea of replacing sticky portions of the peptides with nonstick analogs. His inspiration came from the kitchen as much as the chemistry lab: nonstick cookware is coated with fluorinated polymers, plastic-like compounds composed of chains of carbon atoms completely surrounded by fluorine atoms.

The fluorine not only makes Teflon slippery, it also makes the coating inert to almost every known chemical.

When Marsh and co-workers swapped sticky parts of their AMP molecule with nonstick, fluorinated versions, the molecules became much more resistant to proteases.

"The difference was quite striking," said Marsh, a U-M professor of chemistry. "When we treated them with purified proteases, the nonfluorinated AMPs were all degraded within 30 minutes.

Under the same conditions, the fluorinated AMP was completely intact after 10 hours. We think that should make them more effective, as they'll stay around longer in the body.

"We also showed that they seem to be at least as good at killing bacteria as their nonfluorinated counterparts, and for some bacteria they're actually significantly better."

Next, the researchers plan experiments to learn whether Teflon AMPs are also less toxic than their stickier equivalents.

If they are, and if further studies continue to point to their promise, eventually producing large enough quantities of fluorinated AMPs for clinical trials should be quite feasible, Marsh said. Though the research now has obvious practical applications, it started as an exploration in basic science.

"We were just interested in translating useful properties of man-made materials into biological molecules," Marsh said. "But fairly immediately we saw the potential for applying our fundamental science to a very important clinical problem, which is the way that more and more bacteria are becoming resistant to more and more conventional antibiotics."

Marsh's collaborators on this project include associate professor of chemistry Ayyalusamy Ramamoorthy, graduate students Lindsey Gottler and Hyang-Yeol Lee, and Charles Shelburne, an assistant research scientist in the School of Dentistry.

The researchers have funding from the American Heart Association and the National Science Foundation.



Related Links:

E. Neil Marsh

American Chemical Society



Contact: Nancy Ross-Flanigan
Phone: (734) 647-1853

University of Michigan News Service, 412 Maynard, Ann Arbor, MI 48109, [email protected]

--------------------
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.

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AliG
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from: Microbe Magazine - Microbe is the news magazine of the American Society for Microbiology

Fluorinated Antimicrobial Peptide Resists Proteases, Has Elevated Potency

Fluorinating antimicrobial peptides (AMPs) renders them dramatically more resistant to proteolytic enzymes and, in some cases, elevates their antimicrobial potency, according to Neil Marsh and his collaborators at the University of Michigan, Ann Arbor.

They presented their findings during the 234th national meeting of the American Chemical Society, held last August in Boston, Mass.

Although AMPs disrupt negatively charged bacterial membranes, they are not particularly effective against neutral phospholipid cell membranes of humans or other eukaryotes.

Moreover, when administered in very high doses to overcome proteolytic degradation, they begin to exert toxic side effects, such as rupturing red blood cells.

``We knew AMPs have potential to be therapeutic molecules, but they need some tweaking to become bene- ficial therapeutics,'' Marsh says. Typically, such AMPs contain 15 to 30 amino acids, and are highly susceptible to proteases.

Marsh and his collaborators chose to modify a synthetic AMP, called MSI-78 or pexiganan, that is an analog of magainin-2, which can be isolated from frog skin.

The researchers replaced two leucine and two isoleucine residues in MSI-78 with hexafluoroleucine, and named this modified AMP fluorogainin-1.

When MSI-78 is added to liposomes to mimic interactions with bacterial membranes, the proteases trypsin and chymotrypsin degrade it within 30 minutes, whereas fluorogainin-1 remains stable for up to 10 hours.

MSI-78 and fluorogainin-1 are both active when tested against both gram-negative and gram-positive bacterial species, including human pathogens.

For example, the two peptides show similar minimum inhibitory concentrations (MIC) in vitro against Bacillus subtilis, Salmonella enteritis, and Shigella sonnei.

``That was not a guarantee after introducing fluorinated atoms,'' notes Marsh. More surprisingly, fluorogainin-1 kills Klebsiella pneumoniae, whereas MSI-78 is inactive against this pathogen.

Furthermore, fluorogainin-1 kills Staphylococcus aureus at a dose four times lower than does MSI-78, but fluorogainin-1 is less active than MSI-78 against Streptococcus pyogenes.

Fluorinated AMPs ``seem to be at least as good at killing bacteria as their nonfluorinated counterparts, and for some bacteria they may be significantly better,'' Marsh says.

The improved resistance to proteolysis in vitro could mean that fluorinated AMPs will have prolonged bioavailability in vivo.

Although some researchers are investigating AMPs in clinical trials, protease destruction and bioavailability problems constrict their therapeutic range.

Marsh, a chemist, had no particular application in mind when he began exploring how fluorine-containing amino acids change proteins and peptides.

However, he was approached by his office neighbor, Ayyalusamy Ramamoorthy, who was interested in using fluorine as a solid-state nuclear magnetic resonance (NMR) probe for studying the interactions of AMPs with cell membranes.

Working together, they went beyond those narrower goals to address the stability of AMPs and advance them as therapeutic agents.

``Adding peptide modifications that enhance stability of antimicrobial peptides in vivo could represent an advance,'' says Paul McCray, a pediatric pulmonologist at the University of Iowa, Iowa City.

However, animal experiments of effectiveness and safety are needed before embracing this preliminary approach as a therapeutic advance, he cautions.

Chemist Beate Koksch of Free University Berlin, Germany, emphasizes the chemical advantages in making and evaluating fluorinated AMPs.

``Given the ominously increasing resistance against antimicrobial drugs, Marsh's investigations of fluorinated antimicrobial peptides as potential drug candidates against bacterial infections is important,'' she says.

Applying fluorine chemistry ``is an impressive step towards the creation of new peptide-based drugs.'' Further, she notes, fluorine dramatically affects the stability and interactions among peptides into which it is incorporated, and also provides a useful label for spectroscopic analyses.

Carol Potera
Carol Potera is a freelance writer in Great Falls, Mont.

--------------------
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.

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