Drug resistance and cellular adhesion are two key elements of both dissemination and prevalence of the human fungal pathogen Candida albicans. Smi1 belongs to a family of hub proteins conserved among the fungal kingdom whose functions in cellular signaling affect morphogenesis, cell wall synthesis and stress resistance. The data presented here indicate that C. albicans SMI1 is a functional homolog of Saccharomyces cerevisiae KNR4 and is involved in the regulation of cell wall synthesis. Expression of SMI1 in S. cerevisiae knr4Δ null mutants rescued their sensitivity to caspofungin and to heat stress. Deletion of SMI1 in C. albicans resulted in sensitivity to the cell-wall-perturbing compounds Calcofluor White and Caspofungin. Analysis of wild-type and mutant cells by Atomic Force Microscopy showed that the Young’s Modulus (stiffness) of the cell wall was reduced by 85% upon deletion of SMI1, while cell surface adhesion measured by Force Spectroscopy showed that the surface expression of adhesive molecules was also reduced in the mutant. Over-expression of SMI1, on the contrary, increased cell surface adhesion by 6 fold vs the control strain. Finally, Smi1-GFP localized as cytoplasmic patches and concentrated spots at the sites of new cell wall synthesis including the tips of growing hyphae, consistent with a role in cell wall regulation. Thus, Smi1 function appears to be conserved across fungi, including the yeast S. cerevisiae, the yeast and hyphal forms of C. albicans and the filamentous fungus Neurospora crassa.

Abstract
. Purpose of Review
. Human fungal pathogens are rapidly increasing in incidence and readily able to evade the host immune responses. Our ability to study the genetic behind this has been limited due to the apparent lack of a sexual cycle and forward genetic tools. In this review, we discuss the evolution of mating, meiosis, and pathogenesis and if these processes are advantageous to pathogens.
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. Recent Findings
. This review summarises what is currently known about the sexual cycles of two important human fungal pathogens, Candida albicans and Candida glabrata. This includes the identification of parasexual cycle in C. albicans and the observed low levels of recombination in C. glabrata populations.
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. Summary
. In this review, we present what is currently known about the mating types and mating/sexual cycles of two clinically important human fungal pathogens, Candida albicans and Candida glabrata. We discuss the evolution of meiosis using the knowledge that has been amassed from the decades of studying Saccharomyces cerevisiae and how this can be applied to fungal pathogens. We further discuss how the evolution of pathogenesis has played a role in influencing mating processes in human fungal pathogens and compare sexual cycles between C. albicans and C. glabrata, highlighting knowledge gaps and suggesting how these two fungi have evolved distinct mating niches to allow the development of disease in a human host.
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Advances in microfabrication technology, and its increasing accessibility, allow us to explore fungal biology as never before. By coupling molecular genetics with fluorescence live-cell imaging in custom-designed chambers, we can now probe single yeast cell responses to changing conditions over a lifetime, characterise population heterogeneity and investigate its underlying causes. By growing filamentous fungi in complex physical environments, we can identify cross-species commonalities, reveal species-specific growth responses and examine physiological differences relevant to diverse fungal lifestyles. As affordability and expertise broadens, microfluidic platforms will become a standard technique for examining the role of fungi in cross-kingdom interactions, ranging from rhizosphere to microbiome to interconnected human organ systems. This review brings together the perspectives already gained from studying fungal biology in microfabricated systems and outlines their potential in understanding the role of fungi in the environment, health and disease.

. Understanding how single eukaryotic cells self-organize to replicate and migrate is relevant to health and disease. In the fungal pathogen,
. Candida albicans
. the small GTPase, Rsr1, guides the directional growth of hyphae that invade human tissue during life-threatening infections. Rsr1 is a Ras-like GTPase and a homolog of the conserved Rap1 subfamily, which directs migration in mammalian cells. Research into how this single GTPase delivers complex intracellular patterning is challenging established views of GTPase regulation, trafficking, and interaction. Here, we show that Rsr1 directly and indirectly coordinates the spatial and temporal development of key intracellular macrostructures, including septum formation and closure, vacuole dynamics, and nuclear division and segregation, as well as whole-cell morphology by determining branching patterns. Furthermore, we categorize these functions by differential Rsr1 localization and activity state and provide evidence to support the emerging view that the cytosolic pool of Ras-like GTPases is functionally active.
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