THE FAUCI FILES, 3( 72): Mycoplasmas: Is The Real AIDS Paradigm Being Ignored?
August 22, 2000
Duesberg's admonitions about HIV were nothing more than
a German-trained scientist's culturally-tinged sadomasochistic
review of the rigors of reproducible scientific experimentation.
That's just how German scientists are made.
So let's forget about the trumped-up Duesberg drama
that gets replayed over and over ad nauseum by those
who have a vested interest in some pharmaceutical
bonanza, and let's consider the very real possibilities
that Duesberg never did -- and Fauci never will.
"Sit down before fact as a little child, be prepared to give
up every preconceived notion, follow humbly wherever and to
whatever abysses nature leads, or you shall learn nothing."
by Thomas Henry Huxley
The question still unanswered is quite simple: How can a single
viral pathogen like HIV cause a disease state of immunoregulatory
compromise, often fatal, that appears to be dramatically different
in terms of symptomatology, epidemiology and disease trajectory
when one views this "AIDS syndrome" in terms of geopolitical
borders?
So why do so many struggle with such an obvious in-your-face
question? Isn't it obvious that there are co-factors -- perhaps
more than one -- which may offer better targets for extending
the trajectory of this disease than HIV (all quotes hereafter
are from the Baseman and Tully article cited and excerpted below):
"In two other studies using PCR, M. fermentans was
identified in the upper respiratory tract of 20% to 44% of
both healthy and HIV-infected patients and was associated
with acute respiratory distress syndrome in
nonimmunocompromised persons."
"Another area of emerging mycoplasmal infections concerns
immunodeficiency. Although patients with congenital or
acquired disorders of antibody production are susceptible
to a wide variety of microbial infections, the unique
susceptibility of such patients to mycoplasmal infections
is a growing concern, especially considering the number of
occurrences, the types of mycoplasmas involved, and the
difficulties posed in the therapeutic management of such
infections."
"Furthermore, the ability of mycoplasmas to induce a broad
range of immunoregulatory events, mediated by cytokine
production and direct effects on macrophages, B and T
cells, and glial cells, is evidence that mycoplasmas
possess the attributes of primary mediators of pathogenesis.
For example, cytokine production and lymphocyte activation
may either minimize disease through the activation of host
defense mechanisms or exacerbate disease through lesion
development."
The harder question is even more obvious: can a medical
system that defines its "ethical standards" only in terms
of the prevailing "standard of care" be trusted to open
its collective mind to ANY possibilities other than those
which perpetuate that "ethical standard of care"? Isn't
the answer obvious?
"Nonetheless, mycoplasmas remain mysterious and enigmatic,
and the available data and proposed hypotheses that
correlate mycoplasmas with disease pathogenesis range from
definitive, provocative, and titillating to inconclusive,
confusing, and heretical. Controversy seems to be a
recurrent companion of mycoplasmas, yet good science and
openmindedness should overcome the legacy that has burdened
them for decades."
When one considers the fact that mycoplasmas offer the very
best pathogenic cofactor candidate(s) to explain even the
most apparent inconsistencies of AIDS pathogenesis, then
one will find these discussions centered on HIV as the superior,
central and dominant pathogen to be, at best, rather parochial
wastes of time, money and lives.
Given our cultural perversion of the basic notions
of "scientific experimental rigor", one must ask:
Who wants to be the first Mycoplasma Activist?
Meantime, NIH/NIAID Director Dr. Anthony "Mussolini" Fauci
has already taken the lead in turning the mycoplasma issue
into bureaucratic window dressing by adding "Mycoplasma"
to his growing list of go-nowhere emerging disease and
research departments.
W. Fred Shaw, Editor
THE FAUCI FILES
======
Full article is freely available at
http://www.cdc.gov/ncidod/EID/vol3no1/baseman.htm
Mycoplasmas explained in Jan/Mar 1997 Emerging Infectious Diseases
====================================
Emerging Infectious Diseases, Jan-Mar 1997, Volume 3, pp.
21-32.
Mycoplasmas: Sophisticated, Reemerging, and Burdened by
Their Notoriety
Joel B. Baseman(1) and Joseph G. Tully(2)
(1)The University of Texas Health Science Center at San
Antonio, San Antonio, Texas, USA. Email:
baseman@uthscsa.edu
(2)National Institute of Allergy and Infectious Diseases,
Frederick Cancer Research and Development Center,
Frederick, Maryland, USA. Email: jt21c@NIH.GOV
"Sit down before fact as a little child, be prepared to give
up every preconceived notion, follow humbly wherever and to
whatever abysses nature leads, or you shall learn nothing."
Thomas Henry Huxley
INTRODUCTION
Mycoplasmas are most unusual self-replicating bacteria,
possessing very small genomes, lacking cell wall
components, requiring cholesterol for membrane function and
growth, using UGA codon for tryptophan, passing through
"bacterial-retaining" filters, and displaying genetic
economy that requires a strict dependence on the host for
nutrients and refuge. In addition, many of the mycoplasmas
pathogenic for humans and animals possess extraordinary
specialized tip organelles that mediate their intimate
interaction with eucaryotic cells. This host-adapted
survival is achieved through surface parasitism of target
cells, acquisition of essential biosynthetic precursors,
and in some cases, subsequent entry and survival
intracellularly. Misconceptions concerning the role of
mycoplasmas in disease pathogenesis can be directly
attributed to their biological subtleties and to
fundamental deficits in understanding their virulence
capabilities. In this review, we highlight the biology and
pathogenesis of these procaryotes and provide new evidence
that may lead to increased appreciation of their role as
human pathogens. No other group of procaryotes has been
so embroiled in controversy and in establishing a clear
pathogenic niche as the mycoplasmas. Their virulence
determinants are undeniably complex, and their unique
biological properties likely challenge the host differently
from typical bacterial pathogens (1,2). Also, numerous
Mycoplasma species appear to comprise the commensal
microbial flora of healthy persons (3), and the association
of these mycoplasmas with disease complicates the diagnosis
and necessitates extensive and highly specific serologic,
nucleic acid, and epidemiologic data. Nonetheless,
mycoplasmas by themselves can cause acute and chronic
diseases at multiple sites with wide-ranging complications
and have been implicated as cofactors in disease. Recently,
mycoplasmas have been linked as a cofactor to AIDS
pathogenesis and to malignant transformation, chromosomal
aberrations, the Gulf War Syndrome, and other unexplained
and complex illnesses, including chronic fatigue syndrome,
Crohn's disease, and various arthritides (4-8). Even with
mounting evidence of their pervasive and pathogenic
potential, mycoplasmas still evoke the image of a group of
obscure or impotent microorganisms. Yet they are
evolutionarily advanced procaryotes (9-11), and their elite
status as "next generation" bacterial pathogens
necessitates new paradigms in fully understanding their
disease potential. Mycoplasmas, which lack cell walls
but possess distinctive sterol- containing plasma
membranes, are taxonomically separated from other bacteria
and belong to the class Mollicutes (mollis, soft; cutis,
skin). Mollicutes, a term that includes the cell wall-less
procaryotes assigned to numerous genera under the class
Mollicutes and is frequently used interchangeably with
mycoplasmas, are unusual for other biological reasons as
well. They are evolutionary descendants of the low G+C
containing gram-positive bacteria and, through chromosome
reduction, represent the smallest self-replicating life
forms. Their streamlined genome size, which illustrates
extreme biological gene economy, imposes complex
nutritional requirements, such as dependence on external
supplies of biosynthetic precursors, including amino acids,
nucleotides, fatty acids, and sterols. This limited coding
capacity dictates for mycoplasmas a parasitic way of life
that few pathogenic micro-organisms can claim. Therefore,
the view that pathogenic mycoplasmas can grow
"independently" requires an appreciation of their fastidious
nature and their intimate dependence upon the host. Because
of these properties, pathogenic mycoplasmas are among the
most difficult micro-organisms to grow from clinical
specimens and remain frequent contaminants of primary and
continuous eucaryotic cell lines and tissue cultures (12).
In some instances, mycoplasma contamination is obvious
since infected eucaryotic cells exhibit aberrant growth,
metabolism, and morphology. However, mycoplasmas often
establish covert and chronic infections of target cells
that lead to either invalid and misleading data or
introduction of mycoplasmas or their products into reagents
dedicated to therapeutic or research purposes. The recent
emphasis on isolating viral agents, such as human
immunodeficiency virus (HIV)-1, from human primary
lymphocytic cells has also demonstrated the frequent
cocultivation of mycoplasmas of human origin. Often, the
unwanted sources of exogenous mycoplasmas are serum
products and filter-"sterilized"(450 nm) solutions;
cross-contamination by already infected cell cultures, viral
stocks, or immunologic preparations; breaks in technique,
including aerosols from the respiratory tract or by mouth
pipetting; ignorance of the mycoplasma problem; or
scientific indifference. Detailed up-to-date reviews
describing the biological and pathogenic properties of
mycoplasmas have been published (1,2,13,14). Our intention
here is to provide a concise historical perspective of the
role of mycoplasmas in human disease; highlight the
discoveries of new Mycoplasma species and their association
with human illness and host conditions that present
problems in detection and treatment; describe selected
biological properties of mycoplasmas consistent with their
intimate host relationship and possible mechanisms of
pathogenicity; and address recent controversies associated
with mycoplasmas as emerging infectious agents. Renewed
attention to these issues may provide the impetus to
demystify mycoplasmas and improve their standing as genuine,
card-carrying pathogens. . . .
AIDS
The role of mycoplasmas in accelerating the
progression of AIDS could not have begun under more
baffling and circuitous conditions. A virus-like agent that
arose through transfection of NIH 3T3 cells with DNA from
Kaposi sarcoma tissues of AIDS patients was later shown to
be M. fermentans. The spotted history of M. fermentans in
rheumatoid arthritis and leukemia and its frequent
contamination of cell cultures, along with its contemporary
link to AIDS, have been considerable impediments to
overcome in its elevation to pathogenic status. However,
careful and convincing independent studies by several
laboratories have implicated M. fermentans as a cause of
systemic infections and organ failure in AIDS patients
(4,74). The isolation of M. fermentans from blood and urine
samples of HIV-infected persons, its detection by PCR and
immunohistochemistry in multiple tissue sites at various
stages of AIDS, and its ability to stimulate CD4+
lymphocytes and other immunomodulatory activities implicate
this Mycoplasma species as a cofactor in AIDS. Consistent
with this possibility, M. fermentans has been shown to act
synergistically with HIV to enhance cytopathic effects on
human CD4+ lymphocytes. Coincident with these studies, a new
Mycoplasma species, Mycoplasma penetrans, also has emerged
as a potential cofactor in AIDS progression (75,76). Its
isolation almost exclusively from the urine of HIV-infected
patients, the extraordinarily high prevalence of antibodies
against this mycoplasma in HIV-infected patients and not in
HIV-seronegative persons, and its capacity to invade target
cells and activate the immune system of HIV-infected
patients at various stages of disease correlate with a
synergistic role with HIV. Other mycoplasmas, including M.
genitalium and Mycoplasma pirum, have also been isolated
from AIDS patients and implicated as potential cofactors.
However, the proposed role of mycoplasmas as infectious
agents and cofactors in AIDS-related disorders still remains
a hypothesis without definitive proof. If cofactors of HIV
are essential to the development of late stages of
HIV-mediated disease, mycoplasmas possess all the
prerequisite properties of the consummate helper. Their
ability to establish covert or overt chronic and persistent
infections with concomitant activation of the immune
system, stimulation of cytokine production, and induction
of oxidative stress correlate with increased HIV
replication and disease progression. Are mycoplasmas
irrelevant to AIDS, or are the clinical and microbiological
correlations sufficient to imply intimate relationships
between HIV and mycoplasmas, especially as the infected
host undergoes immunologic distress? Malignant
Transformation As early as the mid-1960s,
mycoplasma-infected cell lines were associated with
chromosomal aberrations, altered morphologies, and cell
transformation (77,78). These abnormal oncogenic cell traits
continued even after the apparent elimination of
mycoplasmas, and evidence implied increased tumorigenicity
of these transformed cells in animals. This issue has been
revisited in studies demonstrating that longterm,
persistent mycoplasmal infection of mouse embryo cells
initiated a multistage cellular process that resulted in
irreversible cell transformation, karyotypic alterations,
and tumorigenicity in nude mice (6). Do these oncogenic
events associated with mycoplasma-mammalian cell
coincubation relate to the ontogeny of human cancers?
Gulf War Syndrome One of the most controversial current
medical issues is whether the multiple acute and chronic
symptoms found in veterans of the Persian Gulf War were
caused by chemical exposure, infectious agents, or
psychological problems, or whether a Gulf War Syndrome
exists at all. The clinical illness comprises a collection
of symptoms, including chronic fatigue, joint pain,
headaches, and skin rashes. One study suggests that
pathogenic mycoplasmas are responsible for a large number
of cases among veterans, on the basis of DNA hybridization
and the responsiveness of veterans to prolonged antibiotic
treatment (5). Even though the experimental evidence is
sparse and incomplete and well- controlled and detailed
studies by independent laboratories are needed, if the Gulf
War Syndrome has infectious causes, mycoplasmas with their
requisite biological credentials are potential candidates.
Crohn's Disease Several epidemiologic studies correlate
respiratory infections with exacerbation of Crohn's disease
and other chronic inflammatory bowel diseases (7,79).
Acute onset gastrointestinal symptoms in patients with these
diseases are accompanied by seroconversion to specific viral
or M. pneumoniae antigens. As indicated earlier,
mycoplasmas can elicit pleiotropic immune responses and are
difficult to eliminate in patients despite appropriate
antibiotic treatment. Steroid therapy to control
gastrointestinal symptoms in these patients, along with the
multifaceted biological properties associated with
pathogenic mycoplasmas, may precipitate the onset of acute
exacerbations of chronic inflammatory bowel disease.
Rheumatoid Arthritis and Other Human Arthritides The
occurrence of various Mycoplasma and Ureaplasma species in
joint tissues of patients with rheumatoid arthritis,
sexually transmitted reactive arthritis, and other human
arthritides can no longer be ignored (8). A clinical trial
of longterm (6 to 12 months) antibiotic (doxycycline)
therapy before cartilage destruction might prove beneficial
in managing such frequent and often debilitating infections.
Extensive clinical and microbiological evidence indicates
that mycoplasmas alone can elicit a spectrum of illness for
which no other agents are incriminated. The eradication of
these pathogenic mycoplasmas from various tissue sites
requires an intact and functional immune system, although
persons with fully competent immune systems may have
difficulty eliminating mycoplasmas, even with recommended
prolonged drug therapy. Nonetheless, mycoplasmas are still
viewed as subordinates to other infectious agents and are
relegated to a category of commensals that unwittingly
cause disease in patients whose immune systems offer little
resistance to microbial stress and overload. The
fundamental importance of mycoplasmas in specific diseases
of humans, animals, insects, and plants is irrefutable, and
their unique biological properties are consistent with
their intimate association with host target cells. These
remarkable bacteria must continue to receive the scientific
attention of mycoplasmologists, cell culturists,
clinicians, immunologists, and DNA sequencers who most
recently are compiling extensive databases that may
eventually dissect every approachable mycoplasmal element
that defines their biological and genetic being.
Nonetheless, mycoplasmas remain mysterious and enigmatic,
and the available data and proposed hypotheses that
correlate mycoplasmas with disease pathogenesis range from
definitive, provocative, and titillating to inconclusive,
confusing, and heretical. Controversy seems to be a
recurrent companion of mycoplasmas, yet good science and
openmindedness should overcome the legacy that has burdened
them for decades.
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