There are greater than 100 species of Candida but only C. albicans is regularly isolated from humans, 
either as a member of the normal flora or from ill patients. Infections by C. albicans have increased in 
incidence over the last 20 years as more and more medical advances provide opportunities for the 
organism to colonise ill patients such that C. albicans is now the most common fungal infection in 
humans. The reasons must lie partly with the fact that C. albicans is readily isolated as a member of the 
normal flora of humans (mouth, gut and genitourinary tract) and any reduction in colonisation resistance 
by antibiotics will permit a swift increase in numbers of Candida. Candida albicans causes localised 
infections such as vaginal thrush which occur in otherwise healthy people, but is also an important cause 
of systemic disease in hospitalised patients. The risk of colonisation by an endogenous organism is 
clearly greater than with exogenously-acquired organisms. Correspondingly, infections by C. albicans
are invariably the same strain as that present in the normal flora and the patient is likely to be colonised 
prior to developing clinical infection. 
In systemic candidosis the site of invasion varies. Where the site of infection seeds directly into the 
bloodstream (for example an infected intravenous cannula), the natural defences of the skin are 
bypassed. Alternatively, invasion from the mucous membranes is likely as these are the normal sites of 
residence for the organism. Once in the bloodstream, the organisms will be distributed throughout the 
body (haematogenous spread) and multiple organs may become infected. 
The virulence factors that have been proposed for C. albicans include the ability of the organism to 
adhere to numerous substrates including the skin, epithelia and IV line plastic, the production of 
proteinase enzymes and the property of dimorphism. As mentioned above, dimorphism is the ability to 
switch from hyphal forms to yeast forms and back again depending on environmental signals, notably 
temperature. When C. albicans is exposed to serum at 37°C it produces hyphal forms which are 
particularly adherent to human tissues. Mutants unable to exhibit the hyphal forms are less virulent in 

animal models than the wild type. Dimorphism is seen in other primary fungal pathogens such as Histoplasma capsulatum where the hyphal form in the soil switches to the yeast form in human tissue. It 
is interesting to note that in C. albicans both hyphal and yeast forms can be observed in infected human 
tissues. The hyphal forms appear early on in the course of an infection and release of the proteolytic 
enzymes from the hyphal tips can be seen as valuable in the organism penetrating the tissues. The penetration 
of tissues by hyphae is termed thigmotropism. Once simple nutritional substances are available the 
hyphae revert to the yeast form. The signalling systems for Candida are not fully elucidated but the 
principle of the organism adapting to its environment is unmistakable. 
The virulence of C. albicans is complicated due to the genetic variability of the organism. The yeast is 
diploid but considered strictly asexual. Not being tied down to sexual reproduction via meiois, C. 
albicans can vary the level of expression of the virulence genes from the two chromosomes very readily. 
There are implications for the research worker attempting to identify the virulence determinants in 
C. albicans in  that, during the course of an experiment, the yeast may alter the expression of the 
targeted gene under investigation if both alleles are not ablated. 
Having considered three different fungi you will notice that unifying themes are not very evident. The 
primary pathogens, the dermatophytes, do not cause systemic disease whereas the secondary pathogen, 
Candida, does cause invasive, systemic disease. Thus, the severity of the disease is no tan indication that 
the causative agent is a primary pathogen. The exogenous infections, cryptococcosis and aspergillosis, 

are both acquired via the respiratory tract but both neither are infectious between humans. 


From the above examples what are the key virulence factors of fungi that enable human infections? 
Numerous fungi infect plants and cause considerable destruction to industrial farming and horticulture, 
and plant mycologists have considerable expertise on the pathogenic mechanisms of fungal infections. 
With human disease, insufficient research has, to date, been responsible for a limited understanding of 
fungal pathogenesis. Hence, the extent to which pathogenic fungi follow the six characteristic steps 
described for bacterial pathogens is largely speculative. 
•  adhere, 
•  invade, 
•  multiply, 
•  spread, 
•  avoid host defence mechanisms, 
•  exit the host. 
One or more of the steps can be found in most pathogens, but the complete set are difficult to clearly 
identify in many pathogenic fungi (to date anyway). For those fungi that do possess parasitic modes of 

existence, a number of adaptations have accompanied the shift from saprophytic to parasitic existence

Cutler, J.E. (1991) Putative virulence factors of Candida albicans. Annu. Rev. Microbiol.45, 187–218.
Denning, D.W. (1991) Epidemiology and pathogenesis of systemic fungal infections in the
immunocompromised host. J. Antimicrob. Chemother.28, Suppl. B, 1–16.
Fridkin, S.K. and Jarvis, W.R. (1996) Epidemiology of nosocomial fungal infections. Clin.
Microbiol. Rev.9, 499–511.
Hogan, L.H., Klein, B.S. and Levitz, S.M. (1996) Virulence factors of medically important fungi.
Clin. Microbiol. Rev.9, 469–88.
Kobayashi, G.S. and Medoff, G. (1998) Introduction to the fungi and mycoses, in Schaechter, M.,
Engelberg, N.C., Eisenstein, B.I. and Medoff, G. (eds) Mechanisms of Microbial Disease, 3rd
edition, Lippincott, Williams & Wilkins, Baltimore, USA.
Richardson, M.D. (1992) Fungal infections, in McGee, J.O.D., Isaacson, P.G. and Wright, N.A. (eds)
Oxford Textbook of Pathology, Oxford University Press, Oxford, UK. 

Weitzman, I. and Summerbell, R.C. (1995) The dermatophytes. Clin. Microbiol. Rev.8, 240–59. 

Cited By Kamal Singh Khadka
Msc Microbiology, TU.
Assistant Professor In PU, PBPC, PNC, NA, LA.
Pokhara, Nepal.

SOME SUGGESTED REFERENCES: › MicrobiologyBytes Video Library › NCBI › Literature › PubMed Central (PMC


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