In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species.

First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C. auris were isolated from distinct geographical locations. Although C. auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C. auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis. Infections and outbreaks caused by C. auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C. auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C. auris. Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C. auris infections.

The fungal pathogen Candida albicans is frequently associated with catheter-based infections because of its ability to form resilient biofilms. Prior studies have shown that the transcription factor Bcr1 governs biofilm formation in an in vitro catheter model. However, the mechanistic role of the Bcr1 pathway and its relationship to biofilm formation in vivo are unknown. Our studies of biofilm formation in vitro indicate that the surface protein Als3, a known adhesin, is a key target under Bcr1 control. We show that an als3/als3 mutant is biofilm-defective in vitro, and that ALS3 overexpression rescues the biofilm defect of the bcr1/bcr1 mutant. We extend these findings with an in vivo venous catheter model. The bcr1/bcr1 mutant is unable to populate the catheter surface, though its virulence suggests that it has no growth defect in vivo. ALS3 overexpression rescues the bcr1/bcr1 biofilm defect in vivo, thus arguing that Als3 is a pivotal Bcr1 target in this setting. Surprisingly, the als3/als3 mutant forms a biofilm in vivo, and we suggest that additional Bcr1 targets compensate for the Als3 defect in vivo. Indeed, overexpression of Bcr1 targets ALS1, ECE1, and HWP1 partially restores biofilm formation in a bcr1/bcr1 mutant background in vitro, though these genes are not required for biofilm formation in vitro. Our findings demonstrate that the Bcr1 pathway functions in vivo to promote biofilm formation, and that Als3-mediated adherence is a fundamental property under Bcr1 control. Known adhesins Als1 and Hwp1 also contribute to biofilm formation, as does the novel protein Ece1. The formation of biofilms (surface-attached microbial communities) on implanted medical devices such as catheters is a major cause of fungal and bacterial infections. Prior studies of the fungal pathogen Candida albicans have shown that the regulator Bcr1 is required for biofilm formation in vitro, but the mechanism through which it promotes biofilm formation and its significance for biofilm formation in vivo was uncertain. The authors demonstrate that Bcr1 is required for biofilm formation in vivo in a rat model of catheter-based infection. Manipulation of Bcr1 target genes through mutation and gene overexpression shows that the known surface adhesin Als3 has a pivotal role in biofilm formation and that adhesins Als1 and Hwp1 also contribute to biofilm formation. The results thus indicate that adherence is the key property regulated by Bcr1 and highlight a group of adhesins as potential therapeutic targets.