THE INCREASE GROWTH AND MATURATION OF C.

IMMITIS WITH EXPOSURE TO HUMAN SEX HORMONES

PROVIDES A POTENTIAL HYPOTHESIS TO THE HIGH INCIDENCE OF “VALLEY FEVER” SEEN IN MEN AND
PREGNANT WOMEN
INTRODUCTION
Kathryn Choo - Santa Clara University
Coccidioides immitis is a pathogenic fungus most popular for its virulent role in
causing “Valley Fever”, a fungal disease endemic in certain parts of the United States
southwestern region. C. immitis epidemiological specificity in desert areas of the
United States including parts of California, Arizona, New Mexico, Texas and Utah is a
RESULTS RESULTS CONCLUSIONS
result of the fungus rich soil where the fungus can grow and thrive. The mechanism of
Experiment 1.
infection occurs when disruption of this soil caused by farming or even natural
destruction such as earthquakes, release the spores of the fungus and then enter the host •Morphological findings with electron
through inhalation. These dimorphic pathogens evade the immune systems of infected
organisms that cause severe lung disease and can potentially spread to parts of the body
microscope reveals dense septum-associated
causing skin lesions and other life threatening complications in untreated. bodies that are similar to Woronin antibodies
Aside from the unique epidemiological phenomenon of C. immitis which make them share both characteristics of
pathogenicity, other interesting factors have been discovered in showing a possible
increased virulence of the fungus in human hosts. One of these factors includes
Deuteromycota (asexual) and Ascomycota.
findings of increased growth and maturation in the presence of human sex hormones
such as beta active estradiol, progesterone and testosterone. The effects of human sex
•The old reference of C. Immitis as “imperfect
hormones on the fungal growth has been suggested to correlate directly with increased fungi” has continued to confuse taxonomist,
pathogenicity seen in pregnant women (especially in third trimester) and men because
. however recent studies have labeled C. Immitis
of their high levels of these hormones. Is it viable that these human sex hormones could
play such a significant role in fungal growth or are these statistics solely due to low
as asexual forms of “ascomycetes”proposing
immune responses? Scientist have yet to actually confirm a direct correlation between that C. immitis could mistaken human sex
sex hormones and its prominent role in C. immitis growth, however past studies and a hormones for their own mating hormones
still yet an undetermined life cycle/taxonomy of the fungus continue to make this topic
a possible hypotheses to think about in increased virulence seen in patients with
which they use.
“Valley Fever”(Coccidiomycosis).
•Experiments reveal a definite increase in
logathrithmic growth and spherule maturation
size in the presence of specific sex hormones:
beta estradiol, progesterone, and testosterone.
•Furthermore, experiments performed proves
Figure 5. Matured spherule percentage was that C. immitis has a increasingly higher
determined during observation of C. immitis binding affinity for human sex hormones
growth rate of both arthroconidia and compared to several other strains tested.
endospore formation; both resulted in having
the exposure of sex hormone, beta estradiol •All the experimental results shown have
increasing number of mature spores compared provided support and an overall hypothesis to
Figure 3. A log growth response of C. why pregnant women and men show an
to that of those exposed to anti-estrogens,
immitis performed showed an significant
tamoxifen and nafoxidine (represented as T increase in incidence of “Valley Fever”.
increase in growth over 72 hour time period
and N).
when grown in conditions of exposure to
Experiment 2
both beta estradiol(active sex hormone),
Figure 1. Figure 2. Life cycle of testosterone, and progestrone compared to
Microscopic view Dimorphic fungus that of the control (without sex hormone
of culture C. Coccidioides immitis. exposure) and alpha estradiol (non-active sex
Immitis in hormone).
pathogenic
sporulated form.

REFERENCES
METHODS
Figure 6. Electron microscopy of the septum
Three separate experiments performed by different researchers all of Coccidioides immitis resulted in the
Cutler, Jim E., and Keith H. Erke.
combine to the overall support of increased infection of discovery of the presence of structures
coccidiomyocosis seen in pregnant women and men due to human sex
resembling Woronin antibodies. "Ultrastructural Characteristics of Coccidioides
hormone levels effects on fungal growth and maturation.
Immitis, a Morphological Variant of
Cryptococcus Neoformans and Podosypha
Experiment 1
Ravenelli V." Journal of Bacteriology 105.1
In 1981 Researchers at the University of Texas measured the
effects of different sex hormones on the growth and maturation of C.
(1971): 438-44. Print.
immitis along with a few other strains to test if it solely effects C.
immitis. Along with the testing of sex hormones: testosterone, Powell, Bernard L., David J. Drutz, Milton
progesterone, and 17beta-estradiol, they also used controls of the Huppert, and Sung H. Sun. "Relationship of
fungus in a compound with only ethanol or distilled water. Other test
they performed included measuring the effects of sterols without sex Progesterone- and Estradiol-Binding Proteins in
hormone activity (cholesterol and ergosterol) and non-steroidal anti-
estrogens (tamoxifen and nafoxidine) to confirm the positive results of
Coccidioides Immitis to Coccidioidal
the sex hormones. They obtained data of the logarithmic growth under Dissemination in Pregnancy." Infection and
these different conditions, maturation percentage and also analyzed
spore size.
Immunity 40.2 (1983): 478-85. Print.
Experiment 2 Drutz, David J., Milton Huppert, Sung H. Sun,
Exactly a decade before this experiment, in 1971, researchers at and William L. McGuire. "Human Sex
Tulane University School of Medicine performed an experiment,
obtaining electronic microscopic images of the morphological structure Hormones Stimulate Growth and Maturation of
of C. immitis. Their findings on the structure of C. immitis provided Coccidioides Immits." Infection and Immunity
more information allowing researchers to study better the “imperfect”
taxonomy of the fungus. 32.2 (1981): 897-907. Print.
Experiment 3
Pan, Shuchong, Lynee Sigler, and Garry T.
An experiment performed in 1983 by the same researchers at
the University of Texas, further supported the relationship between sex
Cole. "Evidence for Phylogenetic Connection
hormones and its effect on C. immitis growth. They performed an Table 1. Quantitative specific binding of tritiated between Coccidioides Immitis and
experiment testing the binding affinity of different fungal strains Figure 4.Spore formation shown in (A) was
ligands to cytosols of various fungi resulted in Uncinocarpus Reesii (Onygenaceae)."
focusing on C. immitis cytosol on the different sex hormones that exposed to the sex hormone estradiol and
showed positive effects on its fungal growth. determining that C. immitis had significantly Microbiology 140 (1994): 1481-494. Print.
showed significantly larger sized spherules
higher binding affinities for all five hormones
compared to spore formation shown in (B)
tested compared to that of the other fungi tested,
without hormone treatment.
B. dermatidis and T. glabrata.