Antivirulence and avirulence genes in human pathogenic fungi

Figures & data

Box 1. Definitions of concepts.

Pathogenicity: the ability of a microbe to cause damage to a host.

Virulence: the degree of damage a microbe can elicit. This damage manifests as the interruption of normal host function (and usually tissue structure) at any of the cellular, tissue or organ levels, which as clinical manifestations is called disease.

Virulence factor: a microbial attribute that causes damage to a host, either by direct action or indirectly by the host response or by allowing growth and survival when facing the host reaction (the latter is often also called a virulence determinant). The deletion of a virulence factor gene usually reduces virulence.

Antivirulence factor: a microbial attribute that reduces the direct or indirect damage to the human host. The gene that encodes an antivirulence factor is an antivirulence gene, and its deletion or loss leads to an increased virulence.

Avirulence factor: a virulence factor that is recognized by a host specific receptor, which triggers a host immuno response that concludes with the pathogen’s virulence. The gene that encodes an avirulence factor is an avirulence gene.

Figure 1. Illustration of virulence, antivirulence, and avirulence factors and their adaptive consequences within the host. Fungal factors expressed during host–pathogen interactions can lead to three different outcomes. From the pathogen’s perspective, a virulence factor (blue form) can be advantageous to overcome the host immune barrier, invade, or withstand stress conditions during infection. An antivirulence factor, in contrast, might be advantageous outside the host (green squares), but has a detrimental effect within the host, since it lowers the pathogen’s fitness, immune evasion ability or stress resistance. Lastly, a potential virulence factor can lose its function and become detrimental to the pathogen when the host develops specific receptors (purple form). If these recognize the factor or its action in the host, it can trigger an (immune) response that stops the progression of infection and turns the virulence factor into an avirulence factor.

Figure 2. Evolution of a virulence factor to an avirulence factor as a result of antagonistic co-evolution. A virulence factor confers the pathogen with an adaptive advantage within the host environment, which allows the infection to progress. However, frequent host–pathogen interactions act as a selection pressure on the host side to develop a specific defense response. As a result of this co-evolution the host can develop receptors that specifically recognize the pathogen’s virulence factor and trigger a specific (immune) response that counteracts and thereby abolishes the pathogen’s virulence. Note that new avirulence factor can still serve as a virulence factor in susceptible hosts that have not yet developed the specific response.