Candida albicans- An Overview

Candida albicans is a type of yeast or fungus that lives in various parts of the human body, such as the mouth, skin, gut, and vagina . It is usually harmless and controlled by other microbes, but it can cause infections when it grows out of balance . It is an opportunistic pathogen that can affect people with weak or compromised immune systems . It is the most common human fungal pathogen.

Candida albicans can grow in different forms, such as yeast, pseudohyphae, and hyphae . These forms help it to adapt to different environments and host tissues. Candida albicans can also switch between different phenotypes, such as white and opaque cells, which have different mating abilities.

Candida albicans can cause various types of infections, depending on the site and severity of the infection. Some common infections are:

• Thrush: An infection of the mouth and throat that appears as white patches or sores.
• Vaginal yeast infection: An infection of the vagina that causes itching, burning, and discharge.
• Invasive candidiasis: A serious infection that spreads through the bloodstream and affects internal organs, such as the heart, brain, kidneys, and bones .

Candida albicans infections can be diagnosed by microscopic examination, culture, serology, or molecular methods. The treatment depends on the type and severity of the infection. Some common antifungal drugs are nystatin, fluconazole, amphotericin B, and caspofungin .

Candida albicans is a complex and versatile fungus that can cause a range of infections in humans. It is important to understand its biology, pathogenesis, diagnosis, and treatment to prevent and manage these infections effectively.

Candida albicans is a common member of the human gut flora, where it usually lives in harmony with other microorganisms. It can also be found on the mucous membranes of the mouth, throat, vagina, and skin. It is estimated that 40–60% of healthy adults carry C. albicans in their gastrointestinal tract or mouth.

However, C. albicans is not only restricted to the human body. It can also survive outside the human host and be isolated from various sources such as soil, animals, hospitals, inanimate objects, and food. It has a worldwide distribution and can adapt to different environmental conditions.

C. albicans is an opportunistic pathogen that can cause infections when the normal balance of the microbiota is disturbed or when the host`s immune system is weakened. It can cause a range of diseases, from superficial infections of the skin and mucous membranes to systemic infections that affect various organs.

Candida albicans is a polymorphic fungus that can grow in different shapes and sizes depending on the environmental conditions and the stage of its life cycle. The main morphological forms of C. albicans are:

• Yeast form: This is the most common form of C. albicans in culture and in the human body. Yeast cells are small, oval, and unicellular, measuring 2-4 µm in diameter. They reproduce by budding, which means that a daughter cell grows out of the mother cell and then separates. Yeast cells are usually gram-positive, meaning that they stain purple with the Gram stain.
• Pseudohyphal form: This is an intermediate form between yeast and hyphae that occurs when C. albicans is exposed to certain environmental stimuli, such as pH, temperature, or nutrient availability. Pseudohyphae are elongated yeast cells that remain attached to each other by constrictions at the septa (the cross-walls that divide the cells). Pseudohyphae are also gram-positive and have a morphology index (Mi) of about 2-3, which is a mathematical ratio that measures the shape of C. albicans cells based on their length, diameter, and septal diameter.
• Hyphal form: This is the most invasive and pathogenic form of C. albicans that occurs when the fungus penetrates into host tissues or forms biofilms (communities of microorganisms attached to a surface). Hyphae are long, slender, and multicellular filaments that grow by apical extension (the tip of the filament grows and branches out). Hyphae are also gram-positive and have a morphology index of about 4, which indicates a true hyphal shape. Hyphae can be further classified into two types: germ tubes and true hyphae. Germ tubes are the initial hyphal projections that emerge from yeast cells within 2 hours of incubation in human serum at 37°C. Germ tubes are used as a diagnostic test for C. albicans identification. True hyphae are the mature hyphal forms that have parallel walls and septa with pores that allow cytoplasmic continuity between adjacent cells. True hyphae can also produce chlamydospores, which are round, thick-walled structures that serve as survival or dispersal units for C. albicans.

Candida albicans can switch between these morphological forms depending on its genetic and environmental factors. This ability is called phenotypic plasticity and it is one of the main virulence factors of C. albicans, as it allows the fungus to adapt to different host niches and evade immune responses.

Candida albicans can grow on various types of media, depending on the environmental conditions and the nutritional requirements. Some of the common media used to culture C. albicans are:

• Sabouraud dextrose agar (SDA): This is a simple medium that contains glucose and peptone as the main sources of carbon and nitrogen. C. albicans grows as creamy, pasty colonies that are smooth or wrinkled, and have a yeast-like odor. The colonies may also show foot-like extensions from the margin on blood agar .
• CHROMagar Candida: This is a differential medium that contains chromogenic substrates that react with specific enzymes produced by different Candida species. C. albicans produces green colonies on this medium, while other species produce different colors .
• Corn meal agar or rice agar: These are media that induce the formation of chlamydospores by C. albicans. Chlamydospores are thick-walled, spherical structures that are produced terminally or laterally on hyphae or pseudohyphae. They are considered a distinctive feature of C. albicans .

The growth of C. albicans can also be influenced by factors such as temperature, pH, oxygen and carbon dioxide levels, and the presence of serum or other substances. For example, C. albicans can switch from yeast to hyphal form when exposed to higher temperatures (37°C), lower pH (4-6), reduced oxygen or increased carbon dioxide levels, or serum . This switch is called dimorphism and it is associated with increased virulence and invasiveness of C. albicans.

Candida albicans is a polymorphic fungus that can grow in different forms depending on the environmental conditions and the host tissue. The three main forms are yeast, pseudohyphae and true hyphae. Yeast cells are unicellular, oval-shaped and reproduce by budding. Pseudohyphae are elongated cells that remain attached after budding, forming chains or filaments. True hyphae are multicellular, tubular structures that branch and penetrate tissues.

Candida albicans has an asexual life cycle and does not undergo meiosis. However, it can switch between different phenotypes (white and opaque) and mating types (a and α) through epigenetic mechanisms. The white phenotype is more common and forms dome-shaped colonies, while the opaque phenotype is more rare and forms flat colonies. The opaque phenotype is more efficient for mating than the white phenotype.

Mating occurs when two cells of opposite mating types and opaque phenotypes come into contact and fuse to form a tetraploid cell. The tetraploid cell can undergo a parasexual cycle, which involves random chromosome loss without cell division, resulting in a diploid or aneuploid cell. This process generates genetic diversity and may contribute to adaptation and virulence.

Candida albicans can also form biofilms, which are complex communities of cells attached to a surface and embedded in a matrix of extracellular polymeric substances. Biofilms are resistant to antifungal drugs and host immune responses. Biofilm formation involves four stages: adhesion, development, maturation and dispersion. In the adhesion stage, yeast cells attach to a surface using adhesins (cell surface proteins). In the development stage, yeast cells proliferate and produce pseudohyphae and hyphae. In the maturation stage, the biofilm becomes more structured and heterogeneous, with channels for nutrient and waste exchange. In the dispersion stage, yeast cells detach from the biofilm and disseminate to new sites.

Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. C. albicans can grow in several different morphological forms, ranging from unicellular budding yeast to true hyphae with parallel-side walls. The ability to switch between these forms is known as polymorphism and is considered a major virulence factor of C. albicans.

Candidiasis occurs when C. albicans overgrows or invades the mucosal surfaces or the bloodstream of the host, usually due to some alteration in the host immunity, normal flora, or physiology. C. albicans can be transmitted from mother to infant during childbirth, rarely through sexual contact, or from person to person in hospital settings.

C. albicans has several mechanisms and factors that contribute to its pathogenicity, such as:

• Adhesion and invasion: C. albicans can adhere to and invade the epithelial and endothelial cells of the host using various cell surface molecules, such as fibronectin receptors, hydrophobic molecules, and adhesins (e.g., Als3 protein). Als3 protein also acts as an invasin that induces host cells to engulf the fungus by a process called induced endocytosis . C. albicans can also penetrate host tissues by producing hyphae that exert mechanical pressure and secrete hydrolytic enzymes.
• Biofilm formation: C. albicans can form biofilms on various surfaces, such as medical devices, dentures, or mucosal membranes. Biofilms are complex communities of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms provide protection from host defenses, antifungal drugs, and environmental stresses. Biofilm formation involves several steps: yeast cells adhere to a surface, develop into hyphae cells, form a mature biofilm with a heterogeneous structure, and disperse yeast cells to colonize new sites . Biofilm formation is regulated by various transcription factors, such as Bcr1, Tec1, and Efg1.
• Secreted hydrolases: C. albicans secretes three main classes of hydrolases: proteases, phospholipases, and lipases. These enzymes help C. albicans to degrade host proteins, damage host membranes, and acquire nutrients from the environment . C. albicans has 10 secreted aspartyl proteases (Sap1-10), four major classes (A, B, C, and D) of phospholipases, and 10 lipases (Lip1-10).
• Metabolic adaptation: C. albicans can adapt to different metabolic conditions during infection, such as changes in pH, temperature, oxygen levels, and nutrient availability. For example, C. albicans can quickly switch from glycolysis to the glyoxylate cycle when glucose is scarce, allowing it to use alternative carbon sources such as fatty acids . This metabolic flexibility enables C. albicans to infect almost any organ through the bloodstream.
• Phenotypic switching: C. albicans can switch between different phenotypes that have distinct colony morphology, gene expression, and virulence properties. The most common phenotypes are the white and opaque forms, which differ in their mating efficiency, biofilm formation, adhesion, and immune recognition . Phenotypic switching is controlled by epigenetic mechanisms and environmental cues.

These pathogenicity mechanisms enable C. albicans to cause various types of infections in different anatomical sites of the host.

Candida albicans is an opportunistic fungal pathogen that can cause various types of infections in humans, ranging from superficial mucosal candidiasis to life-threatening systemic candidiasis. To achieve this, C. albicans possesses a number of virulence factors that enable it to adhere to host surfaces, invade host tissues, evade host immune responses, and adapt to different environmental conditions . Some of the major virulence factors of C. albicans are:

• Polymorphism: C. albicans can switch between different morphological forms, such as yeast, pseudohyphae, and hyphae, depending on the environmental cues and the stage of infection. This ability allows C. albicans to colonize different niches in the host, penetrate epithelial and endothelial barriers, and escape from phagocytic cells . C. albicans can also undergo phenotypic switching, which is a reversible and heritable change in colony morphology and gene expression that affects its virulence and antifungal susceptibility .

• Adhesins: C. albicans expresses a variety of cell surface proteins that mediate its attachment to host cells and extracellular matrix components, as well as to other fungal cells to form biofilms. One of the most important adhesins is the agglutinin-like sequence (Als) family, which consists of eight members (Als1-Als7 and Als9) that have different binding specificities and functions . For example, Als3 is involved in binding to epithelial cells, endothelial cells, fibrinogen, and laminin, and also acts as an invasin that induces endocytosis of C. albicans by host cells .

• Biofilm Formation: C. albicans can form biofilms on biotic and abiotic surfaces, such as mucosal membranes, indwelling medical devices, and prosthetic implants. Biofilms are complex communities of fungal cells that are embedded in a matrix of extracellular polymeric substances (EPS) and display enhanced resistance to antifungal agents and host defenses . Biofilm formation involves four stages: adhesion, growth, maturation, and dispersal. Several transcription factors (such as Bcr1, Efg1, Tec1, Ndt80, and Brg1) and signaling pathways (such as cAMP-PKA and MAPK) regulate biofilm development in C. albicans .

• Secreted Hydrolases: C. albicans secretes various hydrolytic enzymes that degrade host molecules and facilitate its invasion and nutrient acquisition. The main classes of hydrolases are aspartyl proteases (Saps), phospholipases (Plbs), and lipases (Lips). C. albicans has 10 Saps (Sap1-Sap10), which belong to four subfamilies (A-D) based on their sequence similarity and substrate specificity. Saps degrade host proteins such as immunoglobulins, complement components, cytokines, and extracellular matrix proteins . C. albicans has four Plbs (Plb1-Plb4), which belong to two subfamilies (A-B) based on their localization and activity. Plbs hydrolyze phospholipids in host membranes and modulate host inflammatory responses . C. albicans has 10 Lips (Lip1-Lip10), which belong to three subfamilies (A-C) based on their sequence similarity and substrate specificity. Lips degrade triglycerides and fatty acids in host sebum and skin lipids .

• Metabolic Adaptation: C. albicans can adjust its metabolism to cope with different environmental conditions in the host, such as pH, temperature, oxygen availability, carbon source availability, and nutrient limitation. For example, C. albicans can activate the glyoxylate cycle under glucose starvation to utilize alternative carbon sources such as acetate or fatty acids . C. albicans can also switch from aerobic respiration to fermentation under hypoxic or anaerobic conditions to produce ethanol or lactate as end products . Moreover, C. albicans can modulate its iron uptake mechanisms under iron-replete or iron-depleted conditions by expressing different iron transporters and siderophores .

These virulence factors are not mutually exclusive but rather act synergistically to promote the pathogenesis of C. albicans.

Colonization

This is the initial stage where C. albicans adheres to the epithelial surfaces of the mucous membranes or the skin. The fungus uses various adhesins (such as Als3 protein) to bind to the host cells and extracellular matrix proteins. Colonization also involves nutrient acquisition from the host environment, such as glucose, amino acids and iron. Colonization does not necessarily lead to disease, as C. albicans can exist as a commensal organism in healthy individuals .

Superficial Infection

This is the stage where C. albicans penetrates the epithelial barrier and causes local inflammation and tissue damage. The fungus uses various secreted hydrolases (such as proteases, phospholipases and lipases) to degrade the host proteins and lipids and facilitate invasion. Superficial infection can manifest as oral thrush, vaginal yeast infection, cutaneous candidiasis or nail infection .

Deep-Seated Infection

This is the stage where C. albicans invades deeper tissues and organs, such as the gastrointestinal tract, the respiratory tract, the genitourinary tract, the liver, the spleen and the kidneys. The fungus uses various invasins (such as Als3 protein and Ssa1 heat shock protein) to induce endocytosis or active penetration of host cells. Deep-seated infection can also involve vascular invasion and immune evasion or escape mechanisms. Deep-seated infection can result in endocarditis, gastroenteritis, pneumonia, urinary tract infection or hepatosplenic candidiasis .

Disseminated Infection

This is the most severe and life-threatening stage where C. albicans spreads through the bloodstream and infects multiple organs and systems. The fungus uses various factors (such as biofilm formation, metabolic adaptation and coagulation activation) to enhance its survival and virulence in the blood. Disseminated infection can cause sepsis, meningitis, endophthalmitis or multi-organ failure .

Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida. Some species of Candida can cause infection in people; the most common is Candida albicans. Candida normally lives on skin and inside the body, such as the mouth, throat, gut, and vagina, without causing problems. Candida can cause infections if it grows out of control or if it enters deep into the body. For example, it can cause infections in the bloodstream or internal organs like the kidney, heart, or brain.

There are many forms of candidiasis that affect different parts of the body. The most common types of candidiasis include :

• Mucosal candidiasis: This type of candidiasis affects the mucous membranes of the mouth, throat, esophagus, vagina, and anus. It can cause symptoms such as white patches, redness, soreness, itching, burning, and discharge. Some examples of mucosal candidiasis are:

  • Oral candidiasis (thrush): This is the most common form of mucosal candidiasis. It affects the mouth and throat and can cause white patches on the tongue, cheeks, palate, and gums. It can also cause pain and difficulty swallowing. It is more common in infants, elderly people, people with dentures, people with diabetes, people with dry mouth, and people with weakened immune systems.
  • Esophageal candidiasis: This is a form of thrush that affects the esophagus (the tube that connects the mouth to the stomach). It can cause pain and difficulty swallowing, chest pain, nausea, vomiting, and weight loss. It is more common in people with HIV/AIDS, cancer, or other conditions that impair the immune system.
  • Vulvovaginal candidiasis (vaginitis): This is a common form of mucosal candidiasis that affects the vagina and vulva (the external female genitalia). It can cause itching, burning, redness, swelling, and a thick white discharge that may have a yeasty smell. It can also cause pain during urination or sexual intercourse. It is more common in pregnant women, women who use oral contraceptives or antibiotics, women who have diabetes or hormonal imbalances, and women who have poor hygiene or wear tight clothing.
  • Balanitis: This is a form of mucosal candidiasis that affects the glans penis (the head of the penis). It can cause redness, swelling, itching, burning, and a white or yellowish discharge. It can also cause pain during urination or sexual intercourse. It is more common in uncircumcised men who have poor hygiene or diabetes.
  • Anal candidiasis: This is a form of mucosal candidiasis that affects the anus (the opening where stool leaves the body). It can cause itching, burning, redness, soreness, and a whitish coating around the anus. It can also cause pain during bowel movements or sexual intercourse. It is more common in people who have anal sex or use antibiotics.

• Cutaneous candidiasis: This type of candidiasis affects the skin and nails. It can cause symptoms such as redness, scaling, cracking, itching, burning

To diagnose candidiasis caused by Candida albicans, various specimens can be collected depending on the site of infection, such as exudates, tissues, scrapings, swabs, blood, etc. The specimens can be examined by microscopy, culture, molecular methods or serology.

Microscopy and Staining

The specimens can be examined in wet film with 10% KOH to visualize the pseudohyphae and budding yeast cells of Candida albicans. Gram staining can also be done to show the gram-positive nature of the fungus. Some other stains that can be used are periodic acid-Schiff (PAS), Grocott-Gomori methenamine silver (GMS) and calcofluor white.

Culture

The specimens can be cultured on various media to isolate and identify Candida albicans. Some of the commonly used media are:

• Sabouraud dextrose agar (SDA): This medium supports the growth of most fungi and inhibits the growth of bacteria. Candida albicans produces creamy white, smooth colonies on SDA after 24-48 hours of incubation at 25-37°C.
• CHROMagar: This medium contains chromogenic substrates that differentiate Candida species based on their colony color. Candida albicans produces green colonies on CHROMagar after 24-48 hours of incubation at 35°C.
• Corn meal agar or rice agar: These media are used to induce the formation of chlamydospores by Candida albicans. Chlamydospores are round, thick-walled structures that are produced terminally or laterally by the fungus. They are a distinctive feature of Candida albicans and can help to differentiate it from other Candida species.

Identification of Candida albicans

After isolating Candida albicans from culture, some tests can be performed to confirm its identity. Some of the commonly used tests are:

• Germ tube test: This test is based on the ability of Candida albicans to produce germ tubes (short hyphae) within 2 hours when incubated in human serum at 37°C. The test is positive for Candida albicans and negative for most other Candida species.
• Temperature test: This test is based on the ability of Candida albicans to grow at 42°C, unlike most other Candida species. The test can help to differentiate Candida albicans from Candida dubliniensis, which also produces chlamydospores but does not grow at 42°C.
• Biochemical tests: These tests are based on the fermentation and assimilation of various carbohydrates by Candida species. For example, Candida albicans can ferment glucose and maltose with acid and gas production, but not sucrose and lactose. It also produces a pale pink coloration in tetrazolium reduction medium.

Molecular Methods

These methods are based on the detection and amplification of specific DNA sequences of Candida albicans by using probes or polymerase chain reaction (PCR). These methods are more sensitive and specific than conventional methods, but they are also more expensive and require specialized equipment and expertise. Some examples of molecular methods are:

• DNA probe: This method uses a labeled DNA probe that hybridizes with a complementary DNA sequence of Candida albicans in the specimen or culture. The probe can be detected by fluorescence or chemiluminescence.
• PCR: This method uses primers that anneal with specific DNA sequences of Candida albicans and amplify them by repeated cycles of heating and cooling. The amplified DNA can be detected by gel electrophoresis or hybridization with a probe.

Serology

This method is based on the detection of antibodies or antigens of Candida albicans in the patient`s serum or other body fluids. This method is not very specific or sensitive, as most people have been exposed to Candida albicans as part of their normal flora and have developed immune responses to it. However, some serological tests can be useful in certain situations, such as:

• Skin test: This test uses a purified antigen of Candida albicans that is injected intradermally into the patient`s skin. A positive reaction (induration and erythema) indicates a normal cell-mediated immunity to the fungus. A negative reaction indicates a deficiency or impairment of cell-mediated immunity, which increases the risk of candidiasis.
• ELISA and RIA: These tests use enzyme-linked or radio-labeled antibodies that bind to specific antigens or antibodies of Candida albicans in the patient`s serum or other body fluids. These tests can detect circulating antigens (such as cell wall mannan or cytoplasmic constituents) or antibodies (such as IgG, IgM or IgA) of the fungus. These tests can indicate active or past infection, but they may also cross-react with other fungi or substances.
• 1,3-beta-D-glucan assay: This test uses a reagent that activates factor G of the horseshoe crab coagulation cascade in the presence of beta-D-glucan, a component of the fungal cell wall. The activation leads to gel formation that can be measured turbidimetrically or chromogenically. This test is highly specific and sensitive for invasive fungal infections, including candidiasis, but it may also give false-positive results due to contamination or exposure to certain drugs or substances that contain beta-D-glucan.

The treatment of Candida albicans infections depends on the type, location and severity of the infection, as well as the patient`s age, immune status and underlying conditions. The main classes of antifungal drugs used to treat candidiasis are:

• Polyenes: such as nystatin and amphotericin B. They bind to ergosterol, a component of the fungal cell membrane, and cause leakage of cell contents and cell death. They are effective against most Candida species, but can cause side effects such as kidney damage, fever and chills.
• Azoles: such as fluconazole, itraconazole and ketoconazole. They inhibit the synthesis of ergosterol, disrupting the fungal cell membrane and preventing fungal growth. They are effective against most Candida species, but some strains may be resistant. They can cause side effects such as nausea, headache and liver toxicity.
• Echinocandins: such as caspofungin, micafungin and anidulafungin. They inhibit the synthesis of beta-glucan, a component of the fungal cell wall, leading to cell lysis and death. They are effective against most Candida species, especially those resistant to azoles. They can cause side effects such as rash, diarrhea and infusion reactions.

The following table summarizes some common types of candidiasis and their recommended treatments :

The duration of treatment may vary depending on the type and severity of the infection, the patient`s response and the presence of any complications. The treatment should be continued until the symptoms resolve and the fungal culture is negative. The patient should also follow some general measures to prevent recurrence or spread of the infection, such as:

• Maintaining good oral hygiene and denture care
• Wearing loose-fitting cotton underwear and avoiding tight clothing
• Changing diapers frequently and keeping the diaper area clean and dry
• Avoiding douching, perfumed products or irritants in the genital area
• Controlling blood sugar levels if diabetic
• Taking probiotics or yogurt to restore the normal flora of the gut and vagina
• Avoiding unnecessary use of antibiotics or steroids that can alter the balance of Candida
• Practicing safe sex and using condoms to prevent transmission

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