An Enzyme In Various Fungi Helps Combat Gram-Negative Bacteria
A group of hybrid strains of fungi shows that it has the enzyme
that is an efficient inhibitor of several types of gram-negative bacteria called: metallo - β -lactamases, including New Delhi metallo-B-lactamase-1 (NDM-1). Several
patients at research hospitals with severe infectious were not able to fight against an infection with antibiotics. They had
very little hope of survival. Various antibiotics could not stop the infection from a few negative gram bacteria. When the
patients were fed 20 grams a day of a blend of fungi that showed a success from anecdotal tests with other patients, the patients
were able to combat the infections and survive. This fungi blend is made from seven different hybrid strains
from four different species that came from university research labs. . The assumption is that this enzyme, is in this fungi product that inhibits the resistance. We are
now testing this to determine that this is the mechanism or is there another molecule that is causing the inhibiting of the
gram-negative bacteria resistance to antibiotics.
The research team from McMaster University seemed to have found the enzyme that comes from fungi to support antibiotics
by blocking the chemistry in negative gram bacteria so that it is resistant to antibiotics.
Various fungi from soil proved to be an efficient inhibitor of several types of metallo - β -lactamases, including New Delhi metallor- β -lactamase-1 (NDM-1), according to Gerard Wright at McMaster University
in Hamilton, Ontario, Canada, and his collaborators. Because those β -Lactamases render bacterial pathogens resistant to carbapenem antibiotics, he and his collaborators
are continuing to study this natural product as a candidate to use with carbapenems to overcome that resistance and restore
their clinical usefulness, he says.
our best β -lactam antibiotics and help life
threatening pathogens to spread,” says microbiologist Kim Lewis at Northeastern University in Boston, Massachusetts.
Beta-lactamases are enzymes produced by some bacteria that provide resistance to β-Lacta antibiotics like penicillins,
cephamycins, and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic
resistance by breaking the antibiotics’ structure. These antibiotics all have a common element in their molecular structure:
a four-atom ring known as a β-Lactam. Through hydrolysis, the lactamase enzyme breaks the β-Lactam ring open, deactivating
the molecule's antibacterial properties.
An advantage of this enzyme is
its low molecular weight, which enables it to cross the outer membrane of gram-negative pathogens.
are typically used to treat a broad spectrum of Gram-positive and Gram-negative bacteria.
produced by Gram-negative organisms are usually secreted, especially when antibiotics are present in the environment.
A is an polyamino acid naturally produced by the mold Aspergillus versicolor.
The substance has been reported to inhibit two antibiotic resistance carbapenemase proteins in bacteria, New Delhi metallo-beta-lactamase
1 (NDM-1) and Verona integron-encoded metallo-beta-lactamase (VIM-2), and make those antibiotic-resistant bacteria susceptible
to antibiotics. Aspergillomarasmine A is toxic to leaves of barley and other plants, being termed as "Toxin
C" when produced by Pyrenophora teres.
Aspergillomarasmine A can be made from a culture of molds that
produce it. The liquid culture is filtered. Then from the filtrate, a precipitate is formed using calcium chloride, tricalcium
phosphate and acetone. From the precipitate, the substance is redissolved at pH 9 in water. Then chromatographic separation
in Amberlite IRC 50 with ammonia in water, and finally crystallisation at pH 3.0. At pH 2.5 aspergillomarasmine B crystalises.
Gram negative bacteria have thin cell walls with an outer layer composed of proteins and lypopolysaccharide. This
outer layer sometimes reacts with the immune system, causing inflammation and infection. In addition to preventing the bacteria from staining, the outer membrane of the cell also helps the bacteria
resist an assortment of drugs, making treatment of infections with Gram-negative
bacteria rather challenging.
Some examples of Gram-negative
bacteria include Legionella, Salmonella, and E. Coli. Numerous other pathogens are also Gram-negative, including some forms of meningitis, a number of bacterial
sources of gastrointestinal distress, and spirochetes. Gram-negative
bacteria can be stubborn infectious agents, and many sources of lethal infection are Gram-negative, including the bacteria
which contribute to secondary infections in hospitals and clinics.
1. Potera, Carol. “Natural Product from Soil Fungus Blocks
Metallo-B-Lactamases”. Microbe (Microbe – Vol, 9, Number 10,2014): 398-399.
3. Neu HC (June 1969). "Effect of beta-lactamase location in Escherichia coli on penicillin
synergy". Appl Microbiol 17 (6): 783–6. PMC 377810. PMID 4894721
4. King, Andrew M.; Sarah A. Reid-Yu; Wenliang Wang; Dustin T. King; Gianfranco
De Pascale; Natalie C. Strynadka; Timothy R. Walsh; Brian K. Coombes; Gerard D. Wright (2014). "Aspergillomarasmine A
overcomes metallo-β-lactamase antibiotic resistance". Nature 510 (7506): 503–506.
doi:10.1038/nature13445. ISSN 0028-0836
I.; H.J. Lyngs Jørgensen, I.M. Møller, P. Friis, V. Smedegaard-Petersen (2002). "Optimization of in vitro
growth conditions of Pyrenophora teres for production of the phytotoxin aspergillomarasmine A". Physiological
and Molecular Plant Pathology 60 (3): 131–140. doi:10.1006/pmpp.2002.0383. ISSN 0885-5765
6. Wagman, G.H.; Cooper, R. (1988-12-01). Natural Products Isolation: Separation
Methods for Antimicrobials, Antivirals and Enzyme Inhibitors. Elsevier. p. 499. ISBN 9780080858487. Retrieved 27 June 2014
We have completed in vitro and in vivo studies with various strains of medicinal mushrooms,
deciphered the chemical analyses and took what we found to be the best cases. Ongoing research is being
done with various rare strains of rare species, many of them not commercially available. This involved growing these mushrooms on
various substrates to determine the best substrate for the best strain with the desired outcome that would benefit mammalian
chemistry. We then conducted experiments to determine the best results by giving certain blends of these
rare strains to several cancer patients with remarkable results. The protocol included having individuals refrain from consuming foods
with tryalene and pryalene proteins and foods that promoted inflammation. The research papers analyzed
showed that the higher consumption of some of these rare strains provided better results. Clinical
tests are being planned with other researchers at University Medical Centers.
The rare strains used came from the following species of medicinal mushrooms.
The blends and individual strains were developed to target certain diseases and cancers: Ganoderma Lucidum (Reishi), Lentinus
edodes (Shiitake), Hericium erinaceus (Lion's Mane), Inonotus obliquus (Chaga), Antrodia camphorata (Antrodia), Agaricus muscarius
and californicus (Agarius Blazie), Pleruotus ostreatus (Oyster), Flammulina velutipes and ononidis (Enoki), Cordycep sinensis,
unilateralis and bassiana (Cordycep), Grifola frondusa (Maitake), Schizophyilum communa (Suehirotake) and Poria cocos (Hoelen).
The whole mushroom was used in our studies, not extracts. We are researching the chemistry in these rare strains
to determine the mechanisms that cause these good results.
Disease and Tick-borne Diseases
Other tick-borne pathogens to test for are: Babesia, Human
Granulocytic Anaplasma (HGA), Human Monocy Ahrlichia (HME), Bartonelli and Rickettsia. These other tick-borne diseases
are seen in approximately 20% of the patients with Lyme Disease. The typical first tests to order for the tick-borne diseases
are IFA antibody tests, dependent on the region you live or have traveled in.
Response to Wheat Protein May Provide Clue To Cause of Type 1 Diabetes
Aug 31, 2009
In a Canadian study involving 42 patients with type 1 diabetes, nearly half of the subjects had an abnormal response
to wheat proteins. Scientists at the Ottawa Hospital Research Institute and the University of Ottawa, who conducted the study,
found that the patients' over-reaction to wheat is linked to genes that are associated with type 1 diabetes.
The findings have two implications. First, testing for sensitivity
to wheat could be a way of establishing whether a person is predisposed to acquiring type 1 diabetes. Second, people at risk
for type 1 might forestall its onset by eliminating wheat from their diet.
The presence of wheat generates a response by the body's immune system in the form of attacks
by T cell defenders. The Canadians believe that this constant over-reaction puts a strain on the immune system, eventually
unbalancing it to the point that it attacks other parts of the body, including the pancreas.
Given the small number of patients in the study, lead researcher Dr. Fraser
Scott said that more research would be needed to confirm the link between sensitivity to wheat and the predisposition toward
type 1. He noted, however, that previous research with lab animals has shown that a wheat-free diet reduced the risk of developing
The study was published in the August
2009 issue of Diabetes.
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
The National Institute of Neurological Disorders and Stroke (NINDS) supports basic and clinical
research on brain and nervous system disorders. There is a growing awareness of the importance of diseases of the brain in
our society. In part this arises because our population is aging, and diseases of the brain become more prevalent as one gets
older. It is also due to the growing awareness of the importance of a healthy nervous system in early childhood and the brain's
role in many problems that have not traditionally been considered as biologically based diseases, conditions such as autism
or addiction or Tourette's syndrome. NINDS shares with a number of other Institutes and Centers at NIH responsibility for
research on the brain, and cooperates with them in areas of mutual research interest.
NINDS has responsibility for more than 600 neurological disorders that affect every age of the life
span, ranging from well-known disorders such as stroke, Alzheimer's disease, and epilepsy, which affect millions of Americans,
to a host of less well-known disorders that may affect a only few hundred Americans, but are nevertheless devastating to those
with the disease and to their families. Most NINDS-funded research is conducted by extramural scientists in public and private
institutions, such as universities, medical schools, and hospitals. They compete for grants and contracts that account for
more than 80 percent of the Institute's annual budget. NINDS intramural scientists, working in 22 Institute branches and laboratories,
also conduct a wide array of neurological research, ranging from studies uncovering structure and function in single brain
cells to tests of new diagnostic tools and treatments for those with neurological disease. By supporting and conducting neurological
research, the NINDS seeks better understanding, diagnosis, treatment, and prevention of these disorders.
To achieve this goal, the Institute relies on both clinical and basic investigations.
Clinical research applies directly to disease detection, prevention, and treatment, as in studies of brain imaging techniques
and in trials to test new drugs or surgeries for stroke. Although scientists studying the brain have made astounding progress
in recent years, a great deal is still not known about its complex functions. Basic research pursues an understanding of the
structure and activities of the human nervous system. The answers gained through this research can create the foundation for
diagnosing and treating brain disease in the future. Learning how the brain stores memory, for example, may help scientists
determine what happens when memory fails and may even suggest possible ways to treat certain dementias.
NINDS sponsors a rich portfolio of research focusing on disease and disability associated
with the aging brain, including Parkinson's disease and stroke, two major areas of need and opportunity.
Parkinson's Disease. Parkinson's disease (PD) usually strikes in late middle age and
affects more than a half million Americans. It impairs control of movement, progressing from symptoms such as tremor and muscular
rigidity to total disability and death. Parkinson's disease, like Alzheimer's disease, amyotrophic lateral sclerosis (ALS),
and Huntington's disease, is a neurodegenerative disease, the causes of which remain largely unknown. Clinical trials are
underway to evaluate several pharmaceutical and surgical interventions to treat PD. Promising studies of new drug therapies
for PD are continuing. Scientists conducting basic research studies are investigating the genetic and cellular origins of
the disease, and have discovered the gene for one form of PD. These genetic findings open up the possibility for new understanding
of the disease and development of new therapies.
Stroke. For several
years, NINDS has been reporting significant new findings in the prevention of stroke. In 1995 NINDS-supported research led
to the identification of the first emergency treatment for stroke in which a clot blocks a major brain artery. Clinical trial
results showed that the drug, tissue plasminogen activator (t-PA), increases chances for recovery by at least 30 percent if
given within three hours. The trial findings will guide future attempts to develop additional treatments for stroke. Moreover,
the trial demonstrated how community health care systems can organize to provide swift high quality care. To insure such prompt
treatment, NINDS is working with patient and professional organizations to publicize the research results, helping public
and health care professionals organize acute stroke treatment in a variety of settings.
NINDS also supports research on many neurological disorders that affect the entire lifespan. Examples
Epilepsy. Epilepsy refers to a group of disorders which
have in common recurrent seizures that are usually unprovoked and unpredictable. Seizures are caused by abnormal activity
in the brain and take many forms depending on what parts of the brain are involved. In about half the cases no cause can be
found, but head injuries, brain tumors, lead poisoning, problems in brain development before birth, and certain genetic and
infectious illnesses can all cause epilepsy. Medication controls seizures for the majority of patients, who are otherwise
healthy and able to live full and productive lives. On the other hand, at least 200,000 Americans have seizures more than
once a month. Their lives are devastated by frequent, uncontrollable seizures or associated disabilities. As part of an international
coalition including the Human Genome Project and scientists from Finland, NINDS-supported investigations discovered a gene
for one form of epilepsy. Understanding the processes involved in this form of epilepsy opens up an entirely new area of research
that may provide insights about the cause of many forms of epilepsy. This discovery should lead to a screening test, and perhaps
to a better understanding of what causes epilepsy and to new treatment approaches. In addition, NINDS is conducting and supporting
many ongoing research efforts to identify and test new therapies.
and Spinal Cord Injury. One reason trauma to the central nervous system has such severe consequences is that neurons in the
brain and spinal cord fail to regenerate after damage. Now we know they make unsuccessful attempts to regenerate, and in some
circumstances can be coaxed to regrow. NINDS is encouraging research in several areas with potential for success:
- High dose methylprednisolone, the first therapy to improve the outcome of spinal cord
injury, is now regularly used in emergency rooms. The effects of longer methylprednisolone treatment and of a new class of
drugs are now being studied.
- Efforts to understand
and repair trauma of the brain and spinal cord are continuing, using grafts, nerve bridges, cell implants, cell survival factors,
antibodies, and genetic engineering. The potential use of newly-discovered neural progenitor cells, nerve cells that may have
the capacity to replace cells lost because of trauma, is also under investigation.
- Neuroprosthetic devices connect with the nervous system via electrodes to stimulate muscles or provide
sensory input. For example, a neural prosthesis developed with NINDS support and recently recommended for approval by the
FDA restores hand function to quadriplegics. Future research goals include a splint-free system to allow a paraplegic person
to rise, stand and sit again without assistance, and technologies to control muscles using direct brain signals instead of
a functional neuromuscular stimulation implant.
the Developing Nervous System. More than a third of all genetic disorders affect the nervous system, and hundreds of these
first show symptoms in children. In the past several years, research has rapidly progressed in identifying genes for a number
of these disorders. Approximately 50 genes have been identified. Finding the defective gene that causes a disease is only
a beginning towards developing a therapy, but it allows scientists to develop diagnostic tests, create animal models, learn
how the gene and its protein function to promote health or disease, and pursue a reasoned strategy towards counteracting the
defect. Another very exciting area of research addresses the development of the brain in early life.
The National Academy of Science and reports published by the US Department of Health showed that a variety of proteins
in wheat and rye grains may be the cause of neurological and immune malfunctions and the US department of Mental Health in
the 1960's and 1970's completed clinical studies. The results showed that about 50% of all neurological and
immune malfunctions were eliminated when the patient was on a wheat and rye grain free diet which included refraining
from foods with dirivatives of these grains. This should not be confused with celiac disease which is caused by
a reaction to the gluten protein found in wheat, rye, barley and oats. These studies are being shared with
researchers to hypothosize the best approaches for further study as to the etiology of disease.
University of Maryland School of Medicine Scientists Pinpoint
Critical Molecule to Celiac, Possibly Other Autoimmune Disorders Monday,
September 07, 2009
Alessio Fasano, M.D.
Findings Reveal Further Detail About Protein Linked to Inflammatory Disorders
It was nine years ago
that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played
a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes. Now, scientists
have solved the mystery of zonulin’s identity, putting a face to the name, in a sense. Scientists led by Alessio Fasano,
M.D., have identified zonulin as a molecule in the human body called haptoglobin 2 precursor.
the precise molecule that makes up the mysterious protein will enable a more detailed and thorough study of zonulin and its
relationship to a series of inflammatory disorders. The discovery was reported in a new study by Dr. Fasano, published September
8 in the online version of the Proceedings of the National Academy of Sciences. Dr. Fasano is a professor of pediatrics,
medicine and physiology and director of the Mucosal Biology Research Center and the Center for Celiac Research at the University
of Maryland School of Medicine.
Haptoglobin is a molecule that has been known to scientists for many years. It
identified as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin
molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a permutation found only in humans. It’s
believed the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people
throughout the world.
Dr. Fasano’s study revealed that zonulin is the precursor molecule for haptoglobin
2 — that is, it is an immature molecule that matures into haptoglobin 2. It was previously believed that such precursor
molecules served no purpose in the body other than to mature into the molecules they were destined to become. But Dr. Fasano’s
study identifies precursor haptoglobin 2 as the first precursor molecule that serves another function entirely — opening
a gateway in the gut, or intestines, to let gluten in. People with celiac disease suffer from a sensitivity to gluten.
“While apes, monkeys and chimpanzees do not have haptoglobin 2, 80 percent of human beings have it,” says
Dr. Fasano. “Apes, monkeys and chimpanzees rarely develop autoimmune disorders. Human beings suffer from more than 70
different kinds of such conditions. We believe the presence of this pre-haptoglobin 2 is responsible for this difference between
“This molecule could be a critical missing piece of the puzzle to lead to a treatment for
celiac disease, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production
of zonulin/pre-haptoglobin 2 and to the loss of the protective barrier of cells lining the gut and other areas of the body,
like the blood brain barrier,” says Dr. Fasano.
“The only current treatment for celiac disease
is cutting gluten from the diet, but we have confidence Dr. Fasano’s work will someday bring further relief to these
patients. Zonulin, with its functions in health and disease as outlined in Dr. Fasano’s paper, could be the molecule
of the century,” says E. Albert Reece, M.D., Ph.D., M.B.A., dean of the School of Medicine, vice president for medical
affairs of the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor. Dr. Fasano, as a physician
scientist, fulfills two of the core missions of the University of Maryland School of Medicine: making basic science discoveries
that can impact human health, and finding ways to translate those discoveries into treatments and diagnostic tools.”
People who suffer from celiac disease have a sensitivity to gluten, a protein found in wheat, and suffer
gastrointestinal distress and other serious symptoms when they eat it. In celiac patients, gluten generates an exaggerated
release of zonulin that makes the gut more permeable to large molecules, including gluten. The permeable gut allows
these molecules, such as gluten, access to the rest of the body. This triggers an autoimmune response in which a celiac patient’s
immune system identifies gluten as an intruder and responds with an attack targeting the intestine instead of the intruder.
An inappropriately high level of production of zonulin also seems responsible for the passage through the intestine of intruders
other than zonulin, including those related to conditions such as diabetes, multiple sclerosis and even allergies. Recently,
other groups have reported elevated production of zonulin affecting the permeability of the blood brain barrier of patients
suffering from brain cancer.
“We hope pre-haptoglobin 2 will be a door to a better understanding of
not just celiac disease, but of several other devastating conditions that continue to affect the quality of life of millions
of individuals,” says Dr. Fasano. “This is quite a remarkable molecule that was just flying under the radar. We
would have never have thought it would be the key. Now that we have identified this molecule, we are able to replicate it
in the lab to use for research purposes. We hope to learn much more about it and its potential for treating and diagnosing
celiac disease and other autoimmune conditions. This molecule has opened innumerable doors for our research.”
For video or audio of an interview with Dr. Fasano discussing his study, please see these links:
To view the
interview using Real Player:http://media.umaryland.edu:8080/ramgen/oea/090507-fasano-intvu.rm
Study to Investigate AHCC and the Swine Flu Virus
AHCC is a nutritional food supplement developed using a patented process from the mycelia of
several species of mushrooms including the shiitake mushroom.
Dr. Kenna Stephenson Interview with CBS News YouTube Video
AHCC and the Flu on Fox's Morning Show
Learn more about AHCC from Dr. Fred Pescatore YouTube Video
AHCC- a Powerful Aid in Fighting Viruses
and Infections Total Health Magazine
Mon Jun 1, 2009 5:12pm EDT
studies published in peer-reviewed journals have shown the benefits of
AHCC against influenza, avian flu, west nile virus and MRSA.
BEAVERTON, Ore., June 1
/PRNewswire/ -- A study evaluating the effect of
(Active Hexose Correlated Compound) on supporting the immune system in
response to the swine flu virus will
be conducted at the Southern China
Agricultural University, one of the few research centers in China that have
approved to conduct studies on highly infectious diseases such as the
swine flu. This controlled study will examine
the effects of AHCC when
supplemented to a group of mice infected with the virus.
Two years ago, following the avian flu outbreak, the same university conducted
a study in mice on the effect of AHCC on the bird flu (H5N1) virus. The
findings, published in the Japanese Journal
of Complementary and Alternative
Medicine (Vol. 4, (2007), No. 1 pp. 37-40), demonstrated that AHCC enhanced
resistance against bird flu. Other papers published in peer-reviewed
journals include studies on AHCC and the common
influenza (H1N1), the West
Nile Virus and hospital-borne infections including MRSA.
"The animal study
published by my group in the recent issue of Journal of
Nutrition suggested that dietary supplementation with AHCC may
immunotherapeutic for the West-Nile Virus potentially susceptible
populations." said Tian Wang, Assistant
Professor at the Departments of
Microbiology, Immunology and Pathology at the University of Texas Medical
at Galveston. "So in light of our findings and similar conclusions of
Drexel University's study on influenza, I
think that a study on AHCC and the
swine flu is very timely and likely to yield useful information on the value
of AHCC in combating this virus".
human clinical studies have shown that AHCC activates NK cells and
DC Cells, which are the body's frontline defense
against viruses and
infections. A recent study at the Yale Medical School also showed that AHCC
production of cytokines which act as chemical messengers that
activate the immune system when the body comes under attack.
"AHCC is the only natural compound
that I know of which has been studied not
only for influenza but also for several other important virus strains."
Fred Pescatore, MD, MPH of the Center for Integrative and Complementary
Medicine. "The combination of
the animal research on those specific strains
and the significant clinical data on the efficacy of AHCC in humans makes
compound a very compelling target for further research specifically against
the swine flu."
What is AHCC (Active Hexose Correlated Compound)?
AHCC is a natural compound derived from the hybridization
medicinal mushroom. AHCC is used by hundreds of healthcare
facilities around the world and by hospitals as a part of
a standard regimen
for incoming patients to reduce the risk of hospital infections.
supported by more
than 20 studies published in major peer-reviewed medical
journals (key term
"active hexose correlated compound" at www.PubMed.org).