Sexual reproduction of human fungal pathogens

Abstract

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms.

Figure 1.

Mating in Candida albicans. Mating in Candida albians involves both homozygosis from a/α to a/a or α/α, and a switch from the white to opaque phenotype. (A) Homozygosis from a/α to a/a or α/α results in the loss of the a1-α2 corepressor complex, which represses both mating and switching. (B) Attaining mating competence is a two-step process, involving first homozygosis at the mating type locus, and a second phenotypic switch from the white to opaque phenotype. The latter involves a network of inter-regulatory and autoregulatory transcription factors and chromatin modifications, affected by a number of environmental conditions. (C) The cell biology of mating between opaque a/a and α/α cells is similar to that of S. cerevisiae, but involves long conjugation tubes and the formation of an a/a/α/α daughter cell. (D) The pheromone response pathway for mating activation has been conserved in the hemiascomycetes, so that all components, pheromone to the major targeted transcription factor, are orthologs of those components in the S. cerevisiae response pathway.

Figure 2.

Sexual reproduction in Aspergillus species. Micrograph showing larger, ornamented lenticular ascospores (white arrow) of A. lentulus relative to smaller, globose less-heat-resistant conidia (black arrow). Scale bar, 5 µm. (Image courtesy of C. O’Gorman and S. Swilaiman.)