untitled

The pathogenicity and virulence

determinants of dermatophytes

Pathogenicity is the ability to cause disease, while

virulence factors determine the severity of a disease.

Although this distinction is clear in principle, it is not

always easy in practice without knowledge of specific

genes and gene products that can be manipulated to

establish a direct link between disease and the roles of

pathogenicity/virulence determinants. However, two key

features are thought to contribute to diseases caused

by dermatophytes: (i) their ability to grow on substrates

rich in keratin, and (ii) their significant, although not

absolute, degree of host specialization.

Keratinis a major protein found in skin, nails, and

hair. It is a difficult substrate to degrade, especially when

found in the form of “hard keratin” (e.g. nails, hoofs)

which contains numerous disulfide bonds between the

sulphur-containing amino acids. In laboratory culture

the dermatophytes can grow on keratin as their sole

carbon and energy source, by producing keratinolytic

proteases termed keratinases. This is perhaps a unique

feature of these fungi, because no other fungus is

reported to grow exclusively on proteins. Keratinases

could therefore be virulence determinants of the derm-

atophytes, and an understanding of these enzymes

could lead to the development of vaccines. In a recent

report (Brouta et al. 2002) a metalloprotease (MEP)

genome sequence of the unrelated fungus, Aspergillus

fumigatus, was used as a probe to identify three MEP

genes in a genomic library of Microsporum canis. One

of these genes, MEP3, was found to encode a 43.5-kDa

keratinolytic metalloprotease, and both this protease and

another (termed MEP2) were found to be produced in

vivoduring experimental infection studies on guinea

pigs. This work represents the first report of a gene

family encoding potential virulence determinants in

dermatophytes.

Dermatophytes show a quite significant degree of

host- or habitat-specialization, so they are commonly

grouped into three categories (Box 16.1):

• Anthropophilic(human-loving) species are prim-
  arily parasites of humans and only rarely infect
  other species. They typically cause persistent but
  relatively mild infections. Examples of these fungi
  include:
  
  
  • Epidermophyton floccosum, with a worldwide dis-
    tribution, causing infection of the groin, the body,
    and feet (athlete’s foot);
  
  
  • Trichophyton mentagrophytes and T. rubrum –
    probably the commonest species, with worldwide
    distributions, infecting many body parts.
  
  
  
  


• Zoophilic(animal-loving) species typically infect wild
  or domesticated animals, such as cattle, cats, dogs,
  and horses. They can also be transmitted to humans
  who have very close contact with animals, but these
  infections usually induce a strong inflammatory
  response in the human host and then resolve spon-
  taneously. A classic example is Microsporum canis, com-
  monly acquired by humans who have close contact
  with domestic pets such as cats and dogs.


• Geophilicspecies live in soil and usually degrade
  keratin-containing materials such as feathers and
  hair, but they can occasionally infect human hosts.
  An example is Microsporum gypseumwhich is found
  worldwide but commonly in South America, where
  it is usually acquired from soil but occasionally from
  animals.

The treatments used to control dermatophyte infections

are discussed in Chapter 17. Briefly, because these fungi

cause superficial infections they can be treated by

topical application of oxidizing agents or antibiotics

(e.g. nystatin, amphotericin B). If the infections are

persistent they can be treated by oral administration

326 CHAPTER 16

Box 16.1Some of the main dermatophytic fungi that infect humans.

Anthropophilic

Epidermophyton floccosum

Microsporum audouinii

Microsporum ferrugineum

Trichophyton mentagrophytes

var. interdigitale

Trichophyton rubrum

Trichophyton tonsurans

Geophilic

Microsporum gypseum

(commonly infects humans)

Trichophyton terrestre

Zoophilic

Microsporum canis(cats, dogs)

Microsporum equinum (horses)

Microsporum nanum (soil/pigs)

Microsporum persicolor (rodents)

Trichophyton equinum (horses)

Trichophyton mentagrophytes var.

mentagrophytes (mice, rodents)

Trichophyton verrucosum (cattle)

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