Colletotrichum is an economically important plant pathogenic genus worldwide, but can also have endophytic or saprobic lifestyles. The genus has undergone numerous revisions in the past decades with the addition, typification and synonymy of many species. In this study, we provide an account of the 190 currently accepted species, one doubtful species and one excluded species that have molecular data. Species are listed alphabetically and annotated with their habit, host and geographic distribution, phylogenetic position, their sexual morphs and uses (if there are any known). There are eleven species complexes in Colletotrichum and 23 singleton species. The main characters of each species complex are detailed with illustrations. Phylogenetic trees are provided for the whole genus and each species complex. Genes and combination of genes that can be used for identification of the species complexes are suggested. Specific genes that can be used in species identification are given when possible.

Aspergillus fumigatus is an important opportunistic fungal pathogen. The cAMP-dependent protein kinase (PKA) signaling pathway plays an important role in regulating morphology, growth, and virulence in a number of fungal pathogens of plants and animals. We have constructed a mutant of A. fumigatus that lacks the regulatory subunit of PKA, pkaR, and analyzed the growth and development, sensitivity to oxidative damage, and virulence of the mutant, along with those of the wild type and a complemented mutant. Both growth and germination rates of the mutant are reduced, and there are morphological abnormalities in conidiophores, leading to reduced conidiation. Conidia from the ⌬pkaR mutant are more sensitive to killing by hydrogen peroxide, menadione, paraquat, and diamide. However, the hyphae of the mutant are killed to a greater extent only by paraquat and diamide, whereas they are less susceptible to the effects of hydrogen peroxide. In an immunosuppressed mouse model, intranasally administered conidia of the mutant are significantly less virulent than those of the wild type or a complemented mutant. Unregulated PKA signaling is detrimental to the virulence of A. fumigatus, perhaps through the reduced susceptibility of the mutant to damage by oxidizing agents and reduced growth kinetics.Aspergillus fumigatus is an important fungal pathogen of immunocompromised hosts (23,34). Despite the recent introduction of newer antifungals with anti-Aspergillus activity, the morbidity and mortality of invasive aspergillosis (IA) remains high, especially once the infection has disseminated (7). In nature, the fungus plays a key role in the compost cycle by recycling carbon and nitrogen from plant material (24, 42). In this environment, A. fumigatus is likely to be exposed to broad fluctuations in pH, temperatures up to 50°C, and reactive oxygen species (24,33,45). These stressors are not unlike the kinds of factors an organism might encounter in vivo (13). Therefore, adaptive mechanisms that confer resistance to environmental stress may contribute to the efficient colonization and persistence of the organism in the human host.The cyclic AMP-dependent protein kinase (PKA) is a wellknown regulator of the stress response in eukaryotes. PKA is a heterotetramer, made up of a dimer of regulatory subunits and two catalytic subunits. Fungal regulatory subunits are homologues of mammalian type II subunits, based on the autoinhibition site (29). When cAMP binds to the regulatory subunits, a conformational change occurs, which releases the catalytic subunits to autophosphorylate and to phosphorylate downstream targets. PKA signaling in Saccharomyces cerevisiae regulates the general stress control pathway (11,26). Mutants lacking BCY1, the gene encoding the regulatory subunit of PKA in S. cerevisiae, have unregulated PKA activity; these mutants are pseudohyphal in morphology and hypersensitive to killing with hydrogen peroxide (15, 44).The PKA pathway also regulates morphology and virulence in a number of fungal pathogens of humans and pla...

The Ras family of GTPase proteins has been shown to control morphogenesis in many organisms, including several species of pathogenic fungi. In a previous study, we identified a gene encoding a fungus-specific Ras subfamily homolog, rasB, in Aspergillus fumigatus. Here we report that deletion of A. fumigatus rasB caused decreased germination and growth rates on solid media but had no effect on total biomass accumulation after 24 h of growth in liquid culture. The ⌬rasB mutant had an irregular hyphal morphology characterized by increased branching. Expression of rasB⌬113-135, a mutant transgene lacking the conserved rasB internal amino acid insertion, did not complement the deletion phenotype of delayed growth and germination rates and abnormal hyphal morphology. Virulence of the rasB deletion strain was diminished; mice infected with this strain exhibited ϳ65% survival compared to ϳ10% with wild-type and reconstituted strains. These data support the hypothesis that rasB homologs, which are highly conserved among fungi that undergo hyphal growth, control signaling modules important to the directional growth of fungal hyphae.Aspergillus fumigatus is the predominant mold pathogen of immunosuppressed patient populations (12). This organism inhabits soil and organic debris where it produces conidia, the infective propagules that are disseminated by aerosolization (12). In order for A. fumigatus conidia to cause invasive aspergillosis, inhaled conidia must undergo processes that are essential to the establishment and progression of disease and to growth mechanisms common to all filamentous fungi. First, the conidia must complete germination, a process that involves isotropic growth, mitosis, and emergence of the initial germ tube. In order to continue growth and consequently invade tissue, the nascent germling must elongate by a process termed apical extension. The result of this growth process is long, tube-like hyphae, the characteristic morphology of filamentous fungi. The molecular mechanisms that control germination and apical extension and their contribution to virulence in A. fumigatus remain unknown.Homologs of the Ras family of GTPase proteins have been shown to contribute to morphology and virulence in several pathogenic fungi (14). Control of morphogenetic pathways by Ras proteins can be achieved by several different mechanisms. For example, the RSR1 homologs of Saccharomyces cerevisiae (11), Candida albicans (23), and Ashbya gossypii (3) are hypothesized to control components of the polarisome directly by effecting their recruitment and/or stabilization at the site of polarization. Control of a wider range of developmental processes by Ras homlogs can be seen in both Aspergillus nidulans (6, 18, 21) and A. fumigatus (7). The rasA gene product from both of these filamentous fungi has been implicated in controlling events in germination, including mitosis, as well as in completion of the asexual developmental cycle. Although the mechanism is unknown, the Neurospora crassa NC-ras2 gene, a rasB homolog, has als...

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Patient-derived cell lines and animal models have proven invaluable for the understanding of human intestinal diseases and for drug development although both inherently comprise disadvantages and caveats. Many genetically determined intestinal diseases occur in specific tissue microenvironments that are not adequately modeled by monolayer cell culture. Likewise, animal models incompletely recapitulate the complex pathologies of intestinal diseases of humans and fall short in predicting the effects of candidate drugs. Patient-derived stem cell organoids are new and effective models for the development of novel targeted therapies. With the use of intestinal organoids from patients with inherited diseases, the potency and toxicity of drug candidates can be evaluated better. Moreover, owing to the novel clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 genome-editing technologies, researchers can use organoids to precisely modulate human genetic status and identify pathogenesis-related genes of intestinal diseases. Therefore, here we discuss how patient-derived organoids should be grown and how advanced genome-editing tools may be applied to research on modeling of cancer and infectious diseases. We also highlight practical applications of organoids ranging from basic studies to drug screening and precision medicine.