Candida glabrata: Introduction, Morphology, Pathogenicity, Lab

Introduction

Table of Contents

Candida glabrata is a species of yeast, specifically a type of fungus, that belongs to the Candida genus. It is commonly found in the environment and is also part of the normal microbial flora on the skin and mucous membranes of humans. While it is generally considered to be a commensal organism, meaning it can exist harmoniously with its host without causing harm, C. glabrata has gained significant attention as an opportunistic pathogen in recent years.

As an opportunistic pathogen, C. glabrata is known to cause infections, particularly in individuals with weakened immune systems or underlying health conditions. This includes patients with compromised immune systems due to medical treatments (such as chemotherapy or immunosuppressive therapy), those with chronic diseases (like diabetes), or individuals undergoing prolonged hospitalization.

Yeast cells and hyphae of Candida glabrata in Giemsa stained smear of sputum microscopy at a magnification of 1000X — Fig. Yeast cells and hyphae of *Candida glabrata* in Giemsa stained smear of sputum microscopy at a magnification of 1000X

Candida glabrata infections, known as candidiasis or thrush, can manifest in various parts of the body, such as the bloodstream, urinary tract, mouth, and genital regions. It is noteworthy that Candida glabrata is less common compared to another frequently encountered yeast, Candida albicans, but it has shown increased resistance to certain antifungal medications, posing challenges in the management of infections.

Due to its ability to develop resistance to antifungal drugs, C. glabrata infections may be difficult to treat, necessitating careful selection of appropriate antifungal agents. This makes it important for healthcare professionals to be aware of the potential for C. glabrata infections, particularly in vulnerable patient populations, to diagnose and manage these infections effectively.

Morphology

The morphology of Candida glabrata refers to its physical characteristics, particularly its appearance under a microscope or on culture media. As a yeast species, C. glabrata typically exhibits the following morphological features:

Yeast Cells: Candida glabrata primarily exists in the yeast form, which is the most common and clinically relevant form of this organism. Yeast cells are single-celled, oval to spherical structures. They reproduce by budding, where small daughter cells emerge from the parent cell, giving rise to a characteristic “budding yeast” appearance.
Pseudohyphae Formation: Under certain conditions, C. glabrata can form pseudohyphae. Pseudohyphae are chains of elongated yeast cells that remain attached to each other, resembling a primitive form of hyphal growth. However, this is not as common as in some other Candida species like C. albicans.
Hyphae Formation (Rare): Unlike many other pathogenic Candida species, C. glabrata rarely forms true hyphae, which are elongated filamentous structures. Hyphal formation is more common in Candida albicans, contributing to its invasive nature. The lack of prominent hyphae formation is one of the factors contributing to Candida glabrata‘s relatively lower virulence.
Color and Staining: C. glabrata cells typically appear as round to oval, colorless, or light-pinkish structures when observed under a microscope. In Gram stain, they may show a faint pinkish hue due to the cell wall composition.

Fig. Candida glabrata growth on Muller-Hinton agar (MHA) plate

It’s important to note that Candida glabrata‘s morphology can vary depending on environmental conditions, growth media, and the presence of different factors. Additionally, the yeast-to-hyphal transition is influenced by various factors, including temperature, nutrient availability, and the presence of host factors, among others.

Pathogenicity

The pathogenicity of Candida glabrata refers to its ability to cause disease or infections in humans. C. glabrata is considered an opportunistic pathogen, meaning it is typically harmless in healthy individuals with intact immune systems, but can become pathogenic in certain circumstances, particularly when the host’s immune defenses are compromised. Here are some key aspects of Candida glabrata‘s pathogenicity:

Opportunistic Infections: It is one of the leading causes of opportunistic fungal infections in humans, especially in healthcare settings. It can cause a wide range of infections, including bloodstream infections (candidemia), urinary tract infections (candiduria), thrush (oral candidiasis), and infections of other mucous membranes and internal organs.
Immune System Suppression: Its infections are more common in individuals with weakened immune systems, such as those undergoing immunosuppressive therapies, organ transplant recipients, cancer patients undergoing chemotherapy, and those with HIV/AIDS. Patients with severe underlying diseases, malnutrition, or prolonged hospitalization are also at an increased risk.
Biofilm Formation: It has the ability to form biofilms on various surfaces, including medical devices like catheters, prosthetic devices, and implants. Biofilms provide a protective environment for the yeast cells, making them more resistant to immune responses and antifungal treatments.
Antifungal Resistance: One of the major concerns with C. glabrata infections is its increasing resistance to commonly used antifungal drugs, especially azoles like fluconazole. This can complicate treatment and lead to persistent or recurrent infections.
Interactions with Host Cells: It can adhere to and invade host cells, which facilitates its ability to colonize and cause infection. It can also modulate the host immune response, evading clearance by immune cells.
Association with Other Infections: C. glabrata infections are sometimes associated with other bacterial infections or complications. For example, in patients with bloodstream infections, it can lead to sepsis, a life-threatening condition.
Low Virulence Factors: Compared to other Candida species like Candida albicans, Candida glabrata is considered to have lower virulence factors. It is less likely to form hyphae, a structure associated with tissue invasion and pathogenesis, which may partly explain why it is less invasive in healthy individuals.

Lab Diagnosis

The laboratory diagnosis of Candida glabrata involves several methods to accurately identify and differentiate this yeast species from other Candida species and fungal pathogens. The following are common approaches used in the laboratory:

Microscopic Examination: A direct microscopic examination of clinical specimens, such as blood, urine, or other bodily fluids, can provide preliminary evidence of the presence of yeast cells. A wet mount preparation or Gram stain may reveal characteristic yeast cells with a budding appearance, typical of Candida species.
Culture: Culturing the yeast on appropriate growth media is a fundamental step in the diagnosis. Sabouraud dextrose agar or chromogenic agar, like CHROMagar Candida, are commonly used for this purpose. C. glabrata colonies on these media usually appear as smooth, small, creamy-white to pinkish colonies.
Germ Tube Test: The germ tube test is used to differentiate Candida glabrata from Candida albicans, as most other Candida species, including C. glabrata, do not produce germ tubes. In this test, yeast cells are incubated in human serum, and if germ tubes (hyphal projections) are observed after incubation, it indicates C. albicans. The absence of germ tubes suggests non-albicans Candida species, including C. glabrata.
Biochemical Tests: Several biochemical tests, such as carbohydrate assimilation tests and sugar fermentation tests, can be performed to differentiate Candida species. Commercial identification systems, like VITEK, API, or BD Phoenix, are commonly used in clinical laboratories to accurately identify C. glabrata and other yeast species.
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS): MALDI-TOF MS is a powerful tool used for rapid and accurate identification of Candida species. This method relies on unique mass spectrometry profiles to identify the specific yeast species, including Candida glabrata.
Molecular Methods: Polymerase Chain Reaction (PCR) and DNA sequencing can be employed to detect and identify Candida glabrata in clinical samples. These methods are highly sensitive and specific and can provide accurate results, especially when dealing with mixed infections or when rapid identification is crucial.

Candida glabrata germ tube test (GTT)-Negative — Fig. *Candida glabrata* germ tube test (GTT)-Negative

It’s important to note that some C. glabrata strains can show reduced susceptibility or resistance to antifungal drugs, such as fluconazole. Antifungal susceptibility testing should be performed for clinically significant isolates to guide appropriate treatment decisions.

Treatment

The treatment of Candida glabrata infections can be challenging due to its increasing resistance to antifungal medications, especially azoles like fluconazole. The choice of treatment depends on the site and severity of the infection, the patient’s immune status, and antifungal susceptibility testing results. Here are the main treatment options for C. glabrata infections:

Antifungal Medications: a. Echinocandins: Echinocandin drugs, such as caspofungin, micafungin, and anidulafungin, are considered the first-line treatment for Candida glabrata infections, particularly for candidemia and invasive candidiasis. Echinocandins work by inhibiting the synthesis of the fungal cell wall, and they have shown good activity against many Candida species, including C. glabrata. These drugs are usually preferred when the patient is critically ill or when there is a high suspicion of antifungal resistance. b. Azoles: Azole antifungals, such as fluconazole, voriconazole, and isavuconazole, have been commonly used to treat Candida infections. However, due to the increasing prevalence of azole resistance in Candida glabrata, these drugs are now considered less reliable as first-line therapy. Nonetheless, for mild infections, azoles may still be considered as long as the isolate is known to be susceptible to the specific drug. c. Amphotericin B: Conventional amphotericin B or liposomal amphotericin B can be used as an alternative treatment for Candida glabrata infections, especially when other antifungals are not effective or tolerated. Amphotericin B binds to the fungal cell membrane, leading to its disruption and cell death.
Antifungal Susceptibility Testing: Antifungal susceptibility testing should be performed for clinically significant C. glabrata isolates to guide appropriate treatment choices. This testing helps identify the most effective antifungal agent based on the susceptibility profile of the specific strain.
Combination Therapy: In severe or refractory cases, a combination of antifungal drugs may be considered. Combining different classes of antifungals, such as an echinocandin with an azole or amphotericin B, might have a synergistic effect and improve treatment outcomes.
Duration of Therapy: The duration of antifungal therapy depends on the type and location of the infection and the patient’s response to treatment. Candidemia and invasive candidiasis typically require several weeks of treatment, while other forms of candidiasis may be treated for a shorter duration.
Infection Control Measures: In healthcare settings, implementing strict infection control measures is essential to prevent the spread of C. glabrata and other multidrug-resistant organisms. Hand hygiene, environmental cleaning, and proper use and maintenance of medical devices play a crucial role in reducing the risk of infection.

Prevention

Preventing Candida glabrata infections involves a combination of general infection prevention measures and specific strategies to reduce the risk of fungal infections. Here are some key preventive measures:

Infection Control in Healthcare Settings:
- Hand Hygiene: Healthcare providers should practice proper hand hygiene, including handwashing with soap and water or using alcohol-based hand sanitizers, before and after patient contact.
- Environmental Cleaning: Regular and thorough cleaning of patient care areas, medical equipment, and surfaces can help reduce the spread of C. glabrata and other pathogens.
- Proper Use of Medical Devices: Ensure the appropriate insertion and maintenance of medical devices, such as urinary catheters and intravenous lines, to minimize the risk of invasive candidiasis associated with these devices.
Antifungal Stewardship:
- Rational Use of Antifungals: Implement antifungal stewardship programs in healthcare settings to ensure appropriate use of antifungal medications, which can help reduce the development of drug resistance.
Immune System Support:
- Immunization: Encourage immunization for preventable diseases to reduce the risk of immune compromise.
- Managing Underlying Health Conditions: Properly manage chronic diseases, such as diabetes or HIV/AIDS, to optimize the immune system’s function.
Infection Prevention for High-Risk Individuals:
- Neutropenic Precautions: Implement strict neutropenic precautions for patients with low white blood cell counts, such as those undergoing chemotherapy.
- Protective Isolation: Use protective isolation protocols for highly susceptible patients, such as organ transplant recipients or those with severe immunosuppression.
Avoiding Prolonged Antibiotic Use: Unnecessary or prolonged antibiotic use can disrupt the normal balance of microorganisms in the body, potentially promoting fungal overgrowth. Limiting the use of antibiotics when not absolutely necessary can help reduce the risk of candidiasis.
Probiotics: Some studies suggest that probiotics may help maintain the balance of microbial flora in the body, potentially reducing the risk of fungal infections. However, more research is needed to establish their effectiveness for preventing C. glabrata infections.
Personal Hygiene: Maintaining good personal hygiene, especially in areas where C. glabrata commonly colonizes (e.g., skin folds, genital areas), can help reduce the risk of infection.

Preventing Candida glabrata infections is particularly important in healthcare settings, where vulnerable patients are at an increased risk of acquiring infections. Strict adherence to infection control protocols and vigilant surveillance for fungal infections can significantly contribute to reducing the incidence of C. glabrata and other healthcare-associated infections. Additionally, early identification and appropriate treatment of candidiasis can help prevent the spread of the infection and improve patient outcomes.

Keynotes

Here are some key points (keynotes) on Candida glabrata:

C. glabrata is a species of yeast that belongs to the Candida genus and is commonly found in the environment and on human skin and mucous membranes.
It is an opportunistic pathogen, meaning it can cause infections in individuals with weakened immune systems or underlying health conditions.
It is associated with various infections, including candidemia (bloodstream infection), candiduria (urinary tract infection), oral thrush (oral candidiasis), and infections of other mucous membranes and internal organs.
The yeast cells of C. glabrata are oval to spherical and reproduce by budding, which is a characteristic feature observed under the microscope.
It can form pseudohyphae, but true hyphae formation is rare, distinguishing it from some other pathogenic Candida species.
It is less invasive and has lower virulence factors compared to Candida albicans, but it is a significant concern due to its increasing resistance to antifungal medications, especially azoles.
The diagnosis of C. glabrata involves microscopic examination, culture, biochemical tests, and molecular methods to accurately identify the species.
Treatment of C. glabrata infections is challenging, and first-line therapy often involves echinocandin antifungal drugs due to their efficacy against the organism.
Antifungal susceptibility testing is crucial to guide treatment decisions and address potential resistance issues.
Prevention of Candida glabrata infections involves infection control measures in healthcare settings, appropriate antifungal stewardship, and support for the immune system in high-risk individuals.
C. glabrata infections remain a concern in healthcare settings, and ongoing research and surveillance efforts are essential to address the challenges posed by this opportunistic pathogen.

Candida glabrata: Introduction, Morphology, Pathogenicity, Lab Diagnosis, Treatment, Prevention, and Keynotes