Candida glabrata is a fungus that is one of the most frequent causes of candidiasis worldwide, second only to C. albicans. Categorized as a non-albicans Candida species, it functions as an opportunistic pathogen. While often a harmless part of the normal human microflora, it can cause severe, life-threatening infections in people with compromised immune systems or those who are critically ill. It is a growing concern in hospital environments due to its increasing prevalence and tendency toward antifungal drug resistance, contributing to serious nosocomial infections.
Distinct Biological Traits and Virulence
A defining characteristic of C. glabrata is its haploid genome, unlike many other pathogenic Candida species that are diploid. This single set of chromosomes allows the fungus to acquire and express resistance mutations more readily, contributing to its adaptability and survival under drug pressure. C. glabrata cells grow only as yeast cells (blastoconidia) and generally lack the ability to form hyphae or pseudohyphae, structures typically associated with the virulence of other Candida species.
Despite the absence of hyphal formation, a major virulence factor is the fungus’s ability to adhere firmly to host surfaces and medical devices. This adherence is mediated by glycosylphosphatidylinositol (GPI)-anchored cell wall proteins, known as adhesins, which facilitate binding. This process initiates the formation of biofilms, which are yeast cells embedded in an extracellular matrix. Biofilms protect the fungus against host immune defenses and contribute to antimicrobial tolerance and treatment failure.
A challenge in managing C. glabrata infections is its intrinsic or acquired resistance to azole antifungals, such as fluconazole. This resistance often results from the overexpression of drug transporter genes, like CDR1, which pump the drug out of the fungal cell. Mutations in the azole target enzyme, lanosterol 14α-demethylase (encoded by the ERG11 gene), can also reduce susceptibility by altering the drug’s binding site.
Range of Clinical Infections
C. glabrata is capable of causing clinical disease ranging from superficial mucosal colonization to severe systemic infections. The most serious manifestation is candidemia, a bloodstream infection that is a leading cause of hospital-acquired infections. Candidemia caused by C. glabrata is associated with high mortality rates in critically ill and immunocompromised patients.
The fungus is also a frequent cause of urinary tract infections (UTIs), a condition known as candiduria, especially in patients with indwelling urinary catheters or underlying conditions like diabetes. While often asymptomatic, candiduria can lead to severe complications like ascending infection or pyelonephritis. Furthermore, C. glabrata is often implicated in mucosal infections, including vulvovaginal candidiasis (causing recurrent cases) and oral candidiasis in denture wearers or immunosuppressed individuals.
The presence of indwelling medical devices, such as central venous catheters or prosthetic valves, is a significant risk factor because of the fungus’s ability to form biofilms on these surfaces. Biofilms allow the organism to persist and evade host defenses, acting as a reservoir for systemic dissemination. This ability to thrive in various environments, coupled with drug resistance, makes C. glabrata a persistent clinical threat.
Laboratory Identification and Diagnostic Methods
Timely identification of C. glabrata is necessary for appropriate therapy, given its common resistance to fluconazole. Traditional laboratory methods begin with culturing clinical specimens, such as blood or urine, followed by microscopic examination of the characteristic yeast cells. Biochemical testing relies on the organism’s metabolic profile but often requires several days for definitive species identification.
A more rapid, culture-based technique uses chromogenic agars, such as CHROMagar Candida, where C. glabrata produces a distinctive purple-to-pink colony color. Modern laboratories increasingly rely on rapid, technology-driven methods. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) identifies the fungus by analyzing its protein profile, providing accurate species identification from a culture plate within minutes.
Molecular diagnostics offer the fastest identification directly from clinical samples, such as blood cultures, before the yeast is grown in pure culture. Polymerase Chain Reaction (PCR)-based assays target species-specific DNA sequences in the fungal genome, providing highly specific identification in a matter of hours. Commercial platforms like the T2 Candida panel can detect and identify C. glabrata directly from whole blood, circumventing the lengthy blood culture process, which is a major advantage for patients with severe infections like candidemia.
Antifungal Treatment Protocols and Resistance Management
The treatment of invasive C. glabrata infections is challenging due to the species’ reduced susceptibility to azole drugs. Current clinical guidelines recommend echinocandins as the preferred first-line therapy for invasive candidiasis, including candidemia, when C. glabrata is suspected or confirmed. The echinocandin class (caspofungin, micafungin, and anidulafungin) works by inhibiting the enzyme 1,3-β-D-glucan synthase, which is necessary for cell wall synthesis.
Echinocandins are favored because they demonstrate potent activity against C. glabrata, and resistance to this class, while emerging, is less common. However, the fungus can acquire echinocandin resistance through point mutations in the FKS1 and FKS2 genes, which encode subunits of the glucan synthase enzyme. The emergence of strains resistant to both azoles and echinocandins presents a serious challenge, creating multidrug-resistant isolates.
For infections caused by strains with high-level echinocandin resistance, treatment must be escalated to an alternative drug class, most often Amphotericin B formulations. Amphotericin B, a polyene antifungal, works by binding to ergosterol in the fungal cell membrane, causing cell lysis. This drug can be associated with significant toxicity, necessitating the use of safer liposomal formulations.
Antifungal Susceptibility Testing (AST) determines the minimum inhibitory concentration (MIC) of various antifungals against the specific isolate, guiding the modification or de-escalation of therapy. If the isolate is susceptible to fluconazole, a switch from an echinocandin to high-dose fluconazole may be considered for stable patients to reduce toxicity and cost.