Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/α2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.

By using harmonic radar, we report the complete flight paths of displaced bees. Test bees forage at a feeder or are recruited by a waggle dance indicating the feeder. The flights are recorded after the bees are captured when leaving the hive or the feeder and are released at an unexpected release site. A sequence of behavioral routines become apparent: ( i ) initial straight flights in which they fly the course that they were on when captured (foraging bees) or that they learned during dance communication (recruited bees); ( ii ) slow search flights with frequent changes of direction in which they attempt to “get their bearings”; and ( iii ) straight and rapid flights directed either to the hive or first to the feeding station and then to the hive. These straight homing flights start at locations all around the hive and at distances far out of the visual catchment area around the hive or the feeding station. Two essential criteria of a map-like spatial memory are met by these results: bees can set course at any arbitrary location in their familiar area, and they can choose between at least two goals. This finding suggests a rich, map-like organization of spatial memory in navigating honey bees.

The ability to switch between yeast and hyphal growth forms (dimorphism) is one of the most discussed and best investigated virulence attributes of the human pathogenic fungus Candida albicans. Both morphological forms seem to be important for virulence and have distinct functions during the different stages of disease development, including adhesion, invasion, damage, dissemination, immune evasion and host response. In this review, we will provide an overview of the known and potential roles of C. albicans dimorphism and will discuss the potential benefit of drugs that can inhibit the morphological transition.

Iron sequestration by host iron-binding proteins is an important mechanism of resistance to microbial infections. Inside oral epithelial cells, iron is stored within ferritin, and is therefore not usually accessible to pathogenic microbes. We observed that the ferritin concentration within oral epithelial cells was directly related to their susceptibility to damage by the human pathogenic fungus, Candida albicans. Thus, we hypothesized that host ferritin is used as an iron source by this organism. We found that C. albicans was able to grow on agar at physiological pH with ferritin as the sole source of iron, while the baker's yeast Saccharomyces cerevisiae could not. A screen of C. albicans mutants lacking components of each of the three known iron acquisition systems revealed that only the reductive pathway is involved in iron utilization from ferritin by this fungus. Additionally, C. albicans hyphae, but not yeast cells, bound ferritin, and this binding was crucial for iron acquisition from ferritin. Transcriptional profiling of wild-type and hyphal-defective C. albicans strains suggested that the C. albicans invasin-like protein Als3 is required for ferritin binding. Hyphae of an Δals3 null mutant had a strongly reduced ability to bind ferritin and these mutant cells grew poorly on agar plates with ferritin as the sole source of iron. Heterologous expression of Als3, but not Als1 or Als5, two closely related members of the Als protein family, allowed S. cerevisiae to bind ferritin. Immunocytochemical localization of ferritin in epithelial cells infected with C. albicans showed ferritin surrounding invading hyphae of the wild-type, but not the Δals3 mutant strain. This mutant was also unable to damage epithelial cells in vitro. Therefore, C. albicans can exploit iron from ferritin via morphology dependent binding through Als3, suggesting that this single protein has multiple virulence attributes. Iron is an essential nutrient for all microbes. Many human pathogenic microbes have developed sophisticated strategies to acquire iron from the host as most compartments in the body contain little free iron. For example, in oral epithelial cells intracellular iron is bound to ferritin, a protein that is highly resistant to microbial attack. In fact, no microorganism has so far been shown to directly exploit ferritin as an iron source during interaction with host cells. This study demonstrates that the pathogenic fungus Candida albicans can use ferritin as the sole source of iron. Most intriguingly, C. albicans binds ferritin via a receptor that is only exposed on invasive hyphae. This receptor is Als3, which is a member of the Als-protein family. Als3 was previously demonstrated to be an adhesin with invasin-like properties. Mutants lacking Als3 failed to bind ferritin, grew poorly with ferritin as an iron source and were unable to damage epithelial cells. Strains of the baker's yeast expressing C. albicans Als3, but not two closely related proteins, Als1 or Als5, were able to bind ferritin. Therefore, C. albicans uses an additional morphology specific and unique iron uptake strategy based on ferritin while invading into host cells where ferritin is located.

Candida albicans and C. glabrata are the two most common pathogenic yeasts of humans, yet they are phylogenetically, genetically and phenotypically very different. In this review, we compare and contrast the strategies of C. albicans and C. glabrata to attach to and invade into the host, obtain nutrients and evade the host immune response. Although their strategies share some basic concepts, they differ greatly in their outcome. While C. albicans follows an aggressive strategy to subvert the host response and to obtain nutrients for its survival, C. glabrata seems to have evolved a strategy which is based on stealth, evasion and persistence, without causing severe damage in murine models. However, both fungi are successful as commensals and as pathogens of humans. Understanding these strategies will help in finding novel ways to fight Candida, and fungal infections in general.