untitled

of the antibiotic griseofulvin or by newer, less toxic

drugs such as terebinafine (Chapter 17).

Candida albicans and otherCandida

species

Candida albicansoccurs naturally as a diploid budding

yeaston the mucosal membranes of humans and

other warm-blooded animals. It is a common com-

mensal of humans, being found on the mucosa of the

mouth, gut, or vagina of more than 50% of healthy

individuals. Usually it causes no harm, but a wide

range of predisposing factors can cause it to become

invasive, leading to conditions collectively known

as candidosis. A few other Candidaspecies, such as

C. glabrataand C. tropicalis, cause similar conditions,

but less frequently. Several recent reviews cover

significant aspects of Candidabiology – Brown & Gow

(2001), Calderone & Fonzi (2001), and Douglas

(2003).

The list of clinical manifestations of C. albicansis

extensive. This fungus can cause “thrush” in newborn

babies, when the fungus invades the mucosa of the

mouth and throat, producing speckly white pustules

from which the disease gains its name. This is often

associated with delivery through an infected birth

canal, and the fungus proliferates on the mucosa

before a normal, balanced microbial population has

developed. Candidaalso causes cystitis, and it can

cause inflammation of the mouth (stomatitis) of many

people who wear dentures. This is associated with

several factors, including abrasion caused by the den-

tures, adhesion of Candidacells to the dental plastic,

and probably the closed environment with lack of

“flushing” underneath the denture plate.

People whose hands are frequently exposed to water

can develop Candidainfections of the skin and finger-

nails. In addition, Candidacan be introduced into the

blood through catheters and other surgical procedures,

but the yeast population soon declines when the

catheter is removed. Candidainfection of the gut is

often associated with prolonged antibacterial therapy,

especially with tetracycline antibiotics which suppress

the bacterial population. Stress can be an additional

factor in Candidainfections; for example, astronauts

have been found to develop high populations of C.

albicansduring space flights. And, in extreme cases of

predisposition, such as advanced diabetes, neutrophil

or macrophage disorders, immune disorders, and

malignancies, Candida can grow systemically and

become life-threatening. This catalog of examples

shows that Candidais potentially an ever-present

threat to human wellbeing. An understanding of its

virulence determinants could pave the way for new

approaches to controlling these infections.

The virulence determinants ofCandida

albicans

A large body of evidence suggests that there are two

obvious virulence determinants of C. albicans– its

ability to adherestrongly to epithelia and several

other surfaces, and its ability to undergo a dimorphic

switchbetween a yeast phase and a hyphal or pseudo-

hyphal phase in response to environmental factors.

Adhesins

Despite many years of study on the adhesion of

Candidacells, both in vitroand in vivo, it is still not

possible to define precisely the role that adhesion

plays in Candidainfections, because there seem to be

many interacting factors. Adhesion studies in vitro

show that the yeast cells of C. albicansadhere strongly

to shed epithelial cells of the vagina, and that adhesion

is stronger to cells obtained from pregnant women. The

two commonest cell types in the vaginal epithelium

are the intermediate cells and the superficial cells.

Candidabinds most strongly to the intermediate cells

in vitro, and these cells predominate when there are

high levels of progesterone (for example, during pre-

gnancy or in women who use oral contraceptives).

Progesterone seems to have a direct effect, because

Candidabinds more strongly to the epithelial cells of

nonpregnant women if progesterone is added in vitro.

Additionally, strains of C. albicansfrom active vaginal

infections are found to adhere more strongly in in

vitrostudies than do isolates from healthy people. This

raises the possibility that venereal spread of vaginal

candidosis might involve the transmission of strongly

adherent strains.

These general correlations between in vitroadhesion

and the course of relatively mild clinical infections are

supported by other studies. For example, C. albicans

adheres to cells of the buccal cavity, to the methyl acry-

late resin of dentures, and to the surfaces of catheters.

By using buccal epithelia or denture resin as model

systems in vitro, the adhesion of Candidawas found to

be strongly enhanced if the fungus had been grown

on high levels of galactose, maltose, or sucrose, rather

than on glucose. This is associated with the presence

of mannoprotein adhesinson the surface of the yeast

cells. Nevertheless, the differential effects of sugars

seem to be strain-related, because Candidastrains from

active infections show it frequently, whereas strains from

asymptomatic carriers can show it much less often. Also,

adhesion may be a specific feature of C. albicansrather

than of Candidaspecies in general, because the adhe-

sion of nonpathogenic Candidaspp. or of the non-

pathogenic Saccharomyces cerevisiaeis not markedly

altered when they are grown on different sugars.

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