Antivirulence and avirulence genes in human pathogenic fungi

Abstract

Opportunistic commensal and environmental fungi can cause superficial to systemic diseases in humans. But how did these pathogens adapt to infect us and how does host-pathogen co-evolution shape their virulence potential? During evolution toward pathogenicity, not only do microorganisms gain virulence genes, but they also tend to lose non-adaptive genes in the host niche. Additionally, virulence factors can become detrimental during infection when they trigger host recognition. The loss of non-adaptive genes as well as the loss of the virulence potential of genes by adaptations to the host has been investigated in pathogenic bacteria and phytopathogenic fungi, where they are known as antivirulence and avirulence genes, respectively. However, these concepts are nearly unknown in the field of pathogenic fungi of humans. We think that this unnecessarily limits our view of human-fungal interplay, and that much could be learned if we applied a similar framework to aspects of these interactions. In this review, we, therefore, define and adapt the concepts of antivirulence and avirulence genes for human pathogenic fungi. We provide examples for analogies to antivirulence genes of bacterial pathogens and to avirulence genes of phytopathogenic fungi. Introducing these terms to the field of pathogenic fungi of humans can help to better comprehend the emergence and evolution of fungal virulence and disease.

The Dual Function of the Fungal Toxin Candidalysin during Candida albicans—Macrophage Interaction and Virulence

“…Candidalysin can be seen both as a virulence factor that helps to evade innate immune responses or to breach host barriers, but also as an avirulence factor that can activate host-protective responses in the immunocompetent host and thus limit the pathogen's virulence ( Figure 2) [109,110]. Depending on the infection site, candidalysin exhibits differential effects on fungal virulence.…”

Transient mitochondria dysfunction confers fungal cross-resistance between macrophages and fluconazole

“…However, residing for a long time within the human body requires phenotypic plasticity to survive changing stresses, such as osmotic, ER, and oxidative stress, hypoxia, and starvation (Bliska & Casadevall, 2009; Casadevall, 2008; Gerwien, Skrahina, Kasper, Hube, & Brunke, 2018; Hube, 2009; Krishnan & Askew, 2014; Vylkova & Lorenz, 2014). One mechanism that leads to the better host adaptation and virulence in human pathogenic bacteria and fungi is the inactivation or loss of specific genes, which are then known as antivirulence genes (Bliven & Maurelli, 2012; Siscar-Lewin et al, 2019).…”

“…It was therefore speculated that both genes may contribute to favor C. glabrata in host interactions, in a still unknown manner. Thus, the petite phenotype may constitute a relevant pathogenic form of C. glabrata , and genes involved in mitochondrial function may be considered potential antivirulence genes (Siscar-Lewin et al, 2019).…”

“…Among the strategies that confer pathogenicity, the loss or inactivation of certain genes, termed antivirulence genes, is common in pathogenic microorganisms (Bliven & Maurelli, 2012): Cellular pathways and functions that are normally advantageous for the microbe can become superfluous or even disadvantageous under infection conditions, and the loss or inactivation of their encoding genes becomes adaptive during infection. Several examples of such antivirulence factors are known in human pathogenic fungi, and many more are likely to exist (Siscar-Lewin, Hube, & Brunke, 2019).…”

Fungal infection strategies

“…Such factors have been termed "antivirulence factors" and the respective genes "avirulence genes" [32,33]. In the final paper of this Special Focus, Siskar-Lewin et al discuss how this concept could be transferred to human pathogenic fungi and extend our understanding of host-fungal interaction [34].…”