''Nakaseomyces glabratus'' is a

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

of haploid

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

of the genus ''Nakaseomyces'', previously known as ''Candida glabrata''. Despite the fact that no sexual life cycle has been documented for this species, ''N. glabratus'' strains of both mating types are commonly found. ''N. glabrata'' is generally a

commensal Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit fro ...

of human mucosal tissues, but in today's era of wider human immunodeficiency from various causes (for example, therapeutic immunomodulation, longer survival with various comorbidities such as diabetes, and

HIV infection Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

), ''N. glabratus'' is often the second or third most common cause of

candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...

as an

opportunistic pathogen An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...

. Infections caused by ''N. glabratus'' can affect the urogenital tract or even cause systemic infections by entrance of the fungal cells in the bloodstream ( Candidemia), especially prevalent in immunocompromised patients.

Clinical relevance

''N. glabratus'' is of special relevance in nosocomial infections due to its innately high resistance to antifungal agents, specifically the

azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. T ...

s. Besides its innate tolerance to antifungal drugs, other potential virulence factors contribute to ''N. glabratus''

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

icity. One of them is the expression of a series of adhesins genes. These genes, which in ''N. glabratus'' are mostly encoded in the subtelomeric region of the

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

, have their expression highly activated by environmental cues, so that the organism can adhere to biotic and abiotic surfaces in microbial mats. Adhesin expression is the suspected first mechanism by which ''N. glabratus'' forms fungal

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

s, proved to be more resistant to antifungals than the planktonic cells. ''N. glabratus'' genome frequently undergoes rearrangements that are hypothesized to contribute to the improvement of this yeast's fitness towards exposure to stressful conditions, and some authors consider that this property is connected to the virulence potential of this yeast.

Diagnosis

Cultures are an effective method for identifying non-albicans vaginal infections. Urinalyses are less accurate in this process. The culture may take several days to grow, but the identification of the yeast species is quick once the yeast is isolated. Skin disease diagnosis is difficult, as cultures collected from swabs and biopsies will test negative for fungus and a special assessment is required. Listed under the 'Rare Diseases' database on the NIH web site, ''Torulopsis glabrata'', or ''N. glabratus'' can also be found on the CDC's web site. Although listed as the second most virulent yeast after ''Candida albicans'', the fungus is becoming more and more resistant to common treatments like

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to pr ...

. ''N. glabratus'' resistance to Echinocandin is also increasing, leaving expensive and toxic antifungal treatments available for those infected. Although high mortality rates are listed, assessment of the critical nature of a glabrata infection is a gray area. ''N. glabratus'' ferments and assimilates only glucose and trehalose, opposing to ''Candida'' species and this repertoire of sugar utilization is used by several commercially available kits for identification.

Treatment

A major phenotype and potential virulence factor that ''N. glabratus'' possesses is low-level intrinsic resistance to the

medications, which are the most commonly prescribed antifungal (antimycotic) medications. These medications, including

and ketoconazole, are "not effective in 15–20% of cases" against ''N. glabratus''. It is still highly vulnerable to polyene medications such as

amphotericin B Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...

and

nystatin Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be ...

, along with variable vulnerability to

flucytosine Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...

and caspofungin. However, intravenous amphotericin B is a medication of last resort, causing among other side effects, chronic

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. Amphotericin B vaginal suppositories are used as an effective form of treatment in combination with boric acid capsules as they are not absorbed into the bloodstream. A first-line treatment for vaginal infections may be the use of terconazole 7-day cream. Several courses may be needed. The cure-rate for this treatment is approximately 40%. Recurrences are common, causing chronic infections and spread to other areas such as skin and scalp. Blood infections might be best assessed per symptoms if other areas are involved. An experimental, but effective second-line treatment for chronic infections, is the use of

boric acid Boric acid, more specifically orthoboric acid, is a compound of boron, oxygen, and hydrogen with formula . It may also be called hydrogen borate or boracic acid. It is usually encountered as colorless crystals or a white powder, that dissolve ...

. Compounding pharmacies can create

vaginal suppositories. Use of

Vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...

oil may be used in conjunction to combat irritation.

Amphotericin B Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...

vaginal suppositories have also been used in case studies to treat chronic infections, both symptomatic and asymptomatic.

Borax Borax is a salt ( ionic compound), a hydrated borate of sodium, with chemical formula often written . It is a colorless crystalline solid, that dissolves in water to make a basic solution. It is commonly available in powder or granular for ...

and

may be used for persistent scalp and skin infections.

Phylogenetic relationship

''N. glabratus'' is more closely related to ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...

'' than to ''Candida'' species. In fact, ''N. glabratus'' belongs to the group of '' Nakaseomyces'' inside the

whole genome duplication Paleopolyploidy is the result of genome duplications which occurred at least several million years ago (MYA). Such an event could either double the genome of a single species (autopolyploidy) or combine those of two species (allopolyploidy). Bec ...

clade within

Saccharomycetaceae The Saccharomycetaceae are a family of yeasts in the order Saccharomycetales that reproduce by budding. Species in the family have a cosmopolitan distribution, and are present in a wide variety of habitats, especially those with a plentiful supp ...

. The whole genome duplication event occurred about 90 million years ago, whereas phylogenetic studies indicate that the common ancestor between ''N. glabratus'' and ''C. albicans'' is dated between 200 and 300 million years ago. The largest phylogenetic study to date about ''

Saccharomycotina Saccharomycotina is a subdivision (subphylum) of the division (phylum) Ascomycota in the kingdom Fungi. It comprises most of the ascomycete yeasts. The members of Saccharomycotina reproduce by budding and they do not produce ascocarps (fruitin ...

,'' also known as budding yeasts, indicated in 2018 that the (currently construed) genus ''Candida'' is found in

Pichiaceae The Pichiaceae are a family of yeasts in the order Saccharomycetales. According to the 2007 Outline of Ascomycota, the family contains four genera, but GBIF lists 15 genera. The family was named by Zender in 1925. Genera As listed by GBIF; * '' ...

, CUG-Ser1 clade,

Phaffomycetaceae The Phaffomycetaceae are a family of yeasts in the order Saccharomycetales that reproduce by budding. Species in the family have a widespread distribution. The family are named after '' Phaffomyces'' but it was placed in the Pichiaceae fungi fa ...

and

. Consequently, despite that the name ''Candida'' evokes a unitary notion of

, the pathogenic power of some budding yeasts is a paraphyletic trait shared by several subphyla with different kinds of metabolism.

References

External links

Dr. Fungus's "Candida inconspicua"

Candida genome database

PathoYeastract

''N. glabratus'' genome map
{{Taxonbar, from=Q139137 Fungi described in 1917 Yeasts Fungal pathogens of humans Fungus species