Wednesday, April 25, 2012

Cunninghamella: Fungal Overview

My name is Jeffrey Noland and I am a graduate student (Master's of Science) in the Department of Biological Sciences at Western Illinois University.  This blog is intended to help any person who is interested in the field of medical mycology understand this important fungus.  To aid in understanding specific terms (those highlighted in blue), see the "definitions" section at the end for a description.


GENERAL DESCRIPTION; DISTRIBUTION:


Phylogeny of Cunninghamella species (Murad, et al., 2011)
Cunninghamella spp. is a genus of fungi that is under the taxonomic phylum of Zygomycota and belongs to the class zygomycetes.  This fungus belongs to an order of fungi, Mucorales, that are known to be opportunistic pathogens. Within the family Cunninghamellaceae, Cunninghamella spp. is distributed mainly in tropical and subtropical regions (8,9).  The full taxonomy is listed below.


Domain- Eukarya
Kingdom- Fungi
Phylum- Zygomycota
Class- Zygomycetes
Order- Mucorales
Family- Cunninghamellaceae
Genus- Cunninghamella
Species- C. bertholletiae (example)












Zygosporangia (photo courtesy of Mycology Online)


 When this fungus is cultured, a diagnostic feature is that the colonies are grey or white in color and grow quickly on SDA (Sabouraud's Dextrose Agar).  After its quick growth, the colonies become granulated and very dark in color, which indicates that the fungus has become mature (8).  When cultured, this fungus has raised zygosporangia that are elevated above the surface of the growth media.  Analyzed with microscopy, Cunninghamella can have both zygospores and chlamydoconidia.  These spores are attached to zygosporangia with a width of approximately 20 µm, which are located at the edge of the sporangiophore.  The ends, which contain the zygosporangia, are swelled and produce the tissue responsible for sporulation (8).  No large scale examples (fruiting bodies that are visible environmentally) are known for this fungus.


HABITAT:


Distribution of Cunninghamella spp. (photo courtesy of Discovery Life)
     This genus of fungi can be isolated out of environmental samples, such as soil in tropical and subtropical regions.  Cunninghamella spp. can play on both sides when it comes to the medical field.  It has documented instances where it is an opportunistic pathogen (2), but on the other hand, it has been known to produce compounds that can destroy tumors (2).  Another instance of Cunninghamella acting as a pathogen is in AIDS patients where this zygomycete is an opportunistic pathogen.  For example, Cunninghamella berthollatiae was isolated from a patient suffering from trauma on the thigh (6).  Cunninghamella is also known to be an opportunistic pathogen associated with transplant recipients who are taking immunosuppressants to not reject the transplanted organ (7). Of the known species, only one is considered a human pathogen, Cunninghamella berthollatiae.  


MEDICAL CASES CONCERNING CUNNINGHAMELLA:


Case 1:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532968/pdf/hippokratia-12-043.pdf


Image of a chest X-RAY of a patient with Pulmonary Zygomycosis
(courtesy of www.jgid.org)


     In this case, we have a 10 year old child suffering from a pulmonary zygomycosis.  This case describes the difficulties of diagnosing zygomycoses, mainly due to the rapid growth and necrosis of tissue it infects.  While having leukemia, the patient already has a suppressed immune system leading to the infection.  This article also discusses the increasing occurrence of these types of fungal infections and shows that death, in nearly all of these infections, is common.
     Pulmonary zygomycosis caused by Cunninghamella berthollatiae in a child with actue lymphoblastic leukemia.  Throughout the treatment of this infection, antifungal drugs were used, but to no effect.  The child died from a severe infection that attacked the pulmonary system.  As stated in the paper, nearly all cases of pulmonary zygomycoses that are caused by C. berthollatiae are fatal.  Amphotericin B (an antifungal drug) was not effective enough in the short period of time to cure the patient of infection (1).


NAMING:


     Through Index Fungorum (9),  Cunninghamella is the name that is most commonly used for the fungus because the anamorphic stage is what is most seen.  Approximately 10 species/specific epithets are ranked taxonomically.  Two other names are listed for the teleomorphs:  Choanephora cucurbitarium and Heterobasidion annosum.  Both are currently listed under different families.  C. cucurbitarium is in the family Choanephoraceae, while H. annosum is in the family Bondarzewiaceae.


USES:


     Some of the uses of this genus of fungi that are beyond the scope of medicine, are that some species are used for bioremediation.  In particular, Cunninghamella elegans has been used for the metabolic breakdown of anthracene and phenanthrene (4).  In this study, the authors found that C. elegans was able to metabolize these two compounds that are found throughout the environment as a result of fossil distillation and combustion.  Another study shows that  Cunninghamella elegans has the ability to degrade and metabolize naphthalene, another compound that is very volatile and caustic to the environment, which is a by-product of fossil fuel production and combustion (3).  This study was dual in nature, because it showed the molecular process by which this bioremediation takes place.  C. elegans has a gene that is similar to cytochrome P450 monooxygenase that acts similarly to detoxification pathways in mammals (3).


DEFINITIONS:


SDA:  Sabouraud's Dextrose Agar. SDA is a growth media that is used when culturing fungi.  This was first used by Raimond Jacques Saubouraud in the 1890's.  This media has been used since and has standardized culturing techniques when isolating fungi.


Zygosporangia (pl.): These are structures that belong to this grouping of fungi only.  Here, zygosporangium (sing.) is the location of meiosis or the location of reproductive cell division.


Zygospores:  Sexual spores produced by fungi in the Zygomycota phylum.


Chlamydoconidia:  A type of thick walled spores that are produced during unfavorable conditions (e.g. low nutrient availability, drought, stress...)


Sporulation:  The process by which a fungus generates spores.  This can either be sexual OR asexual spore formation and can indicate whether a fungus has matured or not.  Fungal maturation can be seen when growing on a medium (SDA, environmental substrate, etc) and becomes darker in color over time.


Fruting Body/Bodies:  Structures in fungi that allow for sexual reproduction


Opportunistic Pathogen:  As compared to a true pathogen of humans, this is a pathogen that does not normally infect a human host.  In certain instances, an individual can become compromised, (HIV+, diabetes, taking immune suppressing drugs, etc), which allows for this pathogen to invade and cause illness.  


True Pathogen:  As compared to an opportunistic pathogen (see above), this is a pathogen that can infect a healthy host.  This organism does not require a host to be compromised in some way.  


Immunosuppressants:  Compounds or drugs that suppress the immune system in humans.  These are usually taken when a patient is undergoing cancer treatments (chemotherapy and radiation) or are organ transplant recipients.


Pulmonary:  Location in the body that involves the lungs, heart, and surrounds blood vessels.  


Zygomycosis:  Infection caused by fungi under the Zygomycota phylum.  


Anamorphic:  A developmental stage in fungi that grows rapidly and produces spores that are short lived.  This stage of fungal development is ASEXUAL.


Taxonomy/Taxonomic:  A method of classification of all organisms and biological entities.  This allows for evolutionary relationships to be determined between organisms that share similar biology, but do not have similar genetic structure.  This is done through morphology (physical features and the change from one individual to the next) and molecular (DNA, RNA, Protein codes) data, which allows for proper placement in a specific hierarchical arrangement.  The hierarchical arrangement in taxonomy is as follows:  Domain, Kingdom, Phylum, Class, Order, Family, Genus and Species.  There are various sub- and super- divisions in each ranking (e.g. superfamily or subfamily).


REFERENCES:


(1) Bibashi, E., et al. 2008.  Pulmonary Zygomycosis caused Cunninghamella bertholletiae in a child with acute lymphoblastic leukemia.    
   
(2) Betts, R. E., D. E. Walters, and J. P. Rosazza, 1974. Microbial transformations of antitumor compounds. 1. Conversion of acronycine to 9-hydroxyacronycine by Cunninghamella echinulata.  Journal of Medicinal Chemistry. 17 (6):  599-602

(3) Cerniglia, C. E. and D. T. Gibson, 1977.  Metabolism of naphthalene by cell extracts of Cunninghamella elegans.  Archives of Biochemistry and Biophysics.  186 (1):  121-127.

(4) Cerniglia, C. E. and S. K. Yang, 1984.  Stereoselective metabolism of anthracene and phenathrene by the fungus Cunninghamella elegans.  Applied and Environmental Microbiology 47 (1):  119-124.

(5) Mostaza, J. M., et. al, 1989.  Cutaneoarticular mucormycosis due to Cunninghamella bertholletia in a patient with AIDS


(6) Murad, A. M. A., et. al. 2011. Identification and Characterisation of an Oleaginous Fungus Producing High g-Linoleneic Acid. The Internet Journal of Microbiology.  9 (2): 1-12

(7) Nimmo, G. R., R. F. Whiting, and R. W. Strong, 1988.  Disseminated mucormycosis due to Cunninghamella bertholletiae in a liver transplant recipient.  Postgraduate Medical Journal.  64, 82-84