Dimorphic Fungi:

The members of some fungal species have the ability to grow in the form of yeasts or mycelium depending on the environmental and some internal conditions. This phenomenon, denominated “dimorphism” is not exclusive of some fungal taxa, but examples represent almost all groups. Fungal dimorphism is an important phenomenon from both applied and basic concepts. In the former aspect because a significant number of species pathogenic for plants, animals, and specially humans are dimorphic, the causal agents displaying different forms during their saprophytic and pathogenic stages, and more specifically because it has been demonstrated that inhibition of the dimorphic transition by drugs or mutation blocks the pathogenic development. Regarding the second aspect, the dimorphic transition has all the elements to consider it as an example of cell differentiation, and as such it constitutes a basic model for the study of this important biological phenomenon. In this chapter we analyze dimorphism on this line and propose its study through its division into four blocks of reactions: stimulus reception, translation of the stimulus, change in the developmental program and final outcome.

Paracoccidioides brasiliensis, a pathogenic dimorphic fungus geographically restricted to Latin America, is the causative agent of paracoccidioidomycosis, one of the most recurrent systemic mycoses in the region. Since its first description in 1908 by Adolpho Lutz in Brazil, P. brasiliensis has been considered the only species within the genus Paracoccidioides. Recent phylogenetic data have revealed the presence of cryptic species, namely P. brasiliensis S1, PS2 and PS3, and a well separated species, labeled P. lutzii as a tribute to Lutz. In this review, we bring together information that supports the existence of these new phylogenetic species, as well as summarize extensive works published on molecular aspects of dimorphism and morphogenesis done in classical strains of P. brasiliensis and also in P. lutzii (isolate Pb01). In doing so, we will attempt to analyze possible differences in their metabolic pathways, that may contribute to facilitate species differentiation and help researchers and clinicians to better understand the variety of pathologies so far reported in paracoccidioidomycosis.

Candida albicans is an opportunistic human fungal pathogen that belongs to the Saccharomycetaceae family of ascomycota fungi. C. albicans is responsible for local and systemic infections, mainly in immunocompromised patients. Inside the host, it has the ability to form biofilms, to adapt to different environmental pressures and to switch between yeast and filamentous forms. The molecular mechanisms behind dimorphic transition in C. albicans and its relation to pathogenesis are scientific highlights, and many efforts have been done to understand and identify key regulators in this process. In the present chapter, we review many important regulators of yeast-to-hypha transition in C. albicans, including transcription factors, signaling mediated by cAMP and MAPK pathways, pH dependent morphological transitions and the role of important growth regulators such as polyamines. Even so information on new molecules is still needed to fully understand the mechanisms governing dimorphism in C. albicans.

The pathologist Samuel Taylor Darling discovered in 1905 a new disease caused by a previously not described microrganism that he named Histoplasma capsulatum based on an archaic term for macrophages (Histo), its resemblance to protozoan parasites (plasma), and the apparent presence of a surrounding capsule (capsulatum). However, it turned out that it was a fungus and not encapsulated. In the last few decades, fungal infections have become more widespread due to the AIDS epidemic end to the increase in immune compromised state of patients under chemotherapic treatment, extensive use of antibiotics and organ transplants. In parallel with the developments of molecular biology tools, our knowledge of the mechanism of virulence and host-parasite interactions have also increased significantly. This chapter will highlight the major findings in these areas of investigation focusing on the biology of the virulence determinants of H.capsulatum.

Yarrowia lipolytica is one of the most important non-conventional yeasts that belongs to the Dipodascaceae family of hemiascomycetous fungi. Y. lipolytica is used for both academic and biotechnological applications. Respect to biotech traits, Y. lipolytica is widely used in production of singlecell protein, organic acids and enzymes, also it utilized as heterologous protein expression system, and bioremediation issues, among others. On the other hand, Y. lipolytica has become a model used to study several biological themes such as: dimorphism, protein secretion, gene manipulation, protein expression, peroxisome biogenesis, physiology, genetics, degradation of hydrophobic substrates, and lipid accumulation, etc. Y. lipolytica is a dimorphic organism that grows as a mixture of yeast-like and short mycelial cells. This behavior is influenced by pH, carbon and nitrogen sources, blood serum, citrate, polyamines and anaerobic stress. In the present chapter, we review many important regulators involved in the dimorphic switch in Y. lipolytica. All the knowledge about the yeast-to-hypha transition that has been obtained from this non-pathogenic yeast, providing information that undoubtedly will be useful for the understanding of this phenomenon in important pathogenic organisms.

The thermally dimorphic fungus Sporothrix schenckii is the etiological agent of human and animal sporotrichosis and belongs to the recently proposed Sporothrix complex, which includes other species based on the phylogenetic-species concept. Sporotrichosis is a deep mycosis and clinical manifestations vary from a benign lymphocutaneous form to less frequent disseminated and extracutaneous forms, mainly associated with an immunocompromised host. Animals are also susceptible to S. schenckii infection and cats (Felis catus) are known for greater predisposition to this fungal infection. Only recently has zoonotic transmission of this disease been reported in greater detail in the literature and these new data are changing the epidemiological concept of this mycosis. The gold standard for the diagnosis of sporotrichosis remains fungus isolation from biological specimens, but new diagnostic tools are under development for both human and animal sporotrichosis. The outcome of an infectious disease is not only associated with virulence factors inherent to the pathogen, but also the host immune response. Thermotolerance is described as a virulence factor for S. schenckii and is associated with the capacity of a clinical or environmental isolate to cause host damage. However, the description of new species and genotypes among clinical isolates and the observation that thermotolerant isolates can exhibit differences in virulence using in vivo models strongly supports the concept that other virulence factors could be related to the clinical manifestations or modulate the host immune response. This chapter will address new data in relation to the clinical, epidemiological and biological aspects of S. schenckii.

The zygomycetous fungi occupy many important niches with impact on humans. To list a few, biocatalysts to produce steroids, organic acids, β-carotene, a variety of fermentation products, sources for chitosan and other polymers, biocontrol of insect pest and causative agents of mycoses and storage decays. The zygomycetes are also one of the important tools for recombinant studies. This group consists of ten orders, 32 families, around 124 genera, and 870 species. Earlier, a distinct characteristic viz. the reversible transition between the yeast and hyphal form, was reported in genera Mucor, Cokeromyces and Mycotypha. Similar transitions or giant cell formation now have been reported in other zygomycetes such as Benjaminiella, Rhizopus, Absidia, Chytridiopsis and others. The environmental perturbations triggering vegetative differentiation in different genera and cause-effect relationship of enzymes involved in ammonia assimilation, cell wall synthesis and degradation and other pathways will be discussed. Furthermore, to understand the molecular mechanism underlying this phenomenon the role of different genes such as ornithine decarboxylase, glutamate dehydrogenase, chitin synthase, actin, tubulin and others will be explored. The issues regarding the positioning of dimorphic zygomycetes in the evolution of fungi will also be addressed. The possibility of the use of dimorphism of zygomycetes for various applications will also be given.

Ustilago maydis, a Basidiomycota species, is the causal agent of common smut in corn and teozintle. This fungus has a complex life cycle regulated by two mating factors: a with two alleles involved in mating, and b, multiallelic, involved in mycelial growth and pathogenesis. Two morphological stages can be recognized in the life cycle of the fungus: a yeast-like haploid, saprophytic stage (sporidia), and a mycelial dikaryotic pathogenic stage. Transition of the first one into the latter involves mating between two sporidia containing different a and b alleles, only these dikaryotic cells being infectious, and maintained only in the host, where the diploid stage, a specialized type of spore (teliospore) is formed after cytokinesis. Teliospores germinate to produce haploid sporidia. It is known that pathogenesis and morphogenesis are controlled by the formation of a heterodimer made of two gene products from compatible b genes (bx/by), that acts as a master transcription factor. Nevertheless new data have demonstrated that U. maydis haploid cells may be pathogenic to different plant species under experimental conditions, and that they may grow in the lab in the mycelial form responding to different stimuli: nitrogen starvation, use of fatty acids as C source, and incubation at acid pH. All these data suggest that both, pathogenesis and morphogenesis may occur without the involvement of the heterodimer through a bypass involving a MAPK pathway which is antagonized by a PKA pathway. Different elements such as polyamines, probably DNA methylation, cell wall alterations, but not the pH responsive Pal/Rim pathway are involved in these processes.