Candida tropicalis- An Overview

Candida tropicalis is a species of yeast that belongs to the genus Candida. It is a common fungal pathogen that can cause infections in humans, especially in those with weakened immune systems.

Candida tropicalis is closely related to Candida albicans, the most prevalent Candida species, and shares many features of pathogenicity and clinical presentation. However, C. tropicalis has some distinctive characteristics that make it a significant cause of morbidity and mortality worldwide.

Candida tropicalis can cause superficial and mucosal infections, such as oral thrush, vulvovaginal candidiasis, and skin and nail infections. It can also cause invasive and systemic infections, such as candidemia, disseminated candidiasis, and chronic disseminated candidiasis. These infections can affect various organs and tissues, such as the blood, heart, brain, liver, spleen, kidney, eye, bone, and joint.

Candida tropicalis is one of the most common causes of candidemia, which is the presence of Candida in the bloodstream. Candidemia is a serious and life-threatening condition that requires prompt diagnosis and treatment. Candidemia can lead to sepsis, organ failure, and death.

Candida tropicalis has several virulence factors that enable it to colonize and infect the human host. These include:

• The ability to form blastoconidia (single-celled spores) that are resistant to environmental stress and can adhere to host cells and surfaces.
• The ability to form pseudohyphae (elongated cells) and true hyphae (filamentous cells) that can penetrate host tissues and evade immune responses.
• The ability to produce biofilms (communities of cells embedded in a matrix) that can adhere to medical devices and resist antifungal drugs.
• The ability to secrete enzymes (such as proteases, phospholipases, and hemolysins) that can degrade host tissues and facilitate invasion.
• The ability to switch phenotypes (different forms of appearance) that can adapt to different environmental conditions and evade immune recognition.

Candida tropicalis is also known for its antifungal resistance. It has developed resistance to some of the commonly used antifungal drugs, such as fluconazole, which is a member of the azole class of drugs. Fluconazole resistance can limit the treatment options and increase the mortality rate of C. tropicalis infections. Therefore, new antifungal drugs and strategies are needed to combat this emerging threat.

Candida tropicalis is not only a human pathogen but also an environmental organism. It can be found in various natural habitats, such as seawater, marine sediments, fish intestines, mangrove plants, algae, shrimps, soil, fruit surfaces, and foods. It can also be used for biotechnological purposes, such as bioethanol production and bioremediation.

In this article, we will provide an overview of C. tropicalis based on basic and clinical approaches. We will discuss its habitat, morphology, culture characteristics, pathogenesis, transmission, virulence factors, clinical features, laboratory diagnosis, treatment, antifungal resistance, prevention and control.

Candida tropicalis is one of the fungal species that has been obtained from seawater, sea sediments, mudflats, marine fish intestine, mangrove plants, and marine algae, shrimps. Therefore, they are widely distributed in the tropical and subtropical marine environments. It is also dominantly found in the human gut, fruit surfaces, a variety of foods and soil.

As a normal component of the human microbiota, Candida tropicalis can colonize the gastrointestinal tract, buccal cavity, and urogenital region. It can also cause opportunistic infections when the normal microbiota is disrupted by factors such as immunosuppression, antibiotic use, diabetes mellitus, or catheterization.

Candida tropicalis can also survive in soil and vegetation, where it can interact with plant roots and surfaces. It has been isolated from sediment and vegetation samples from different regions of the world. It can also grow on various carbon sources such as sugars and starches.

Candida tropicalis is an adaptable and versatile species that can thrive in different habitats and conditions. It is important to understand its distribution and ecology to prevent and control its infections in humans and plants.

Candida tropicalis is a yeast-like fungus that belongs to the genus Candida. It is a dimorphic fungus, meaning that it can exist in two different forms: yeast cells and hyphal cells.

Yeast cells are round or oval-shaped, with a diameter of 2-10 µm. They reproduce by budding, either unipolar or bipolar, forming blastoconidia (buds) on stalks. The buds are pigmented and septate, and can form pseudohyphae (chains of elongated buds).

Hyphal cells are filamentous structures that can grow and branch. They are formed by the bud-to-hypha transition (also called morphogenesis), which is a process that involves changes in gene expression, cell wall composition, and morphology. Hyphal cells can penetrate the host tissues and evade the immune system.

Candida tropicalis can also undergo phenotypic switching, which is a reversible change in colony morphology and virulence traits. Phenotypic switching can affect the production of enzymes, adhesion molecules, biofilm formation, and antifungal resistance.

Candida tropicalis can be distinguished from other Candida species by its ability to assimilate soluble starch as a sole carbon source. It also produces acetic acid from glucose fermentation and urease from urea hydrolysis. It does not produce pigments of red, pink, or orange color on culture media.

Candida tropicalis can grow on various standard laboratory media used for cultivating yeasts and fungi, such as:

• Sabouraud dextrose agar (SDA)
• Yeast extract agar (YEA)
• Cornmeal agar (CMA)
• Chromogenic Candida agar (CCA)

On SDA, C. tropicalis produces smooth, creamy, and usually white or cream-colored colonies . However, colony color can vary depending on the specific strain or growth conditions. The colonies are typically smooth and have a moist or creamy texture. This medium suppresses conidia growth but promotes the formation of mycelium.

On YEA, C. tropicalis produces similar colonies as on SDA, but with more abundant blastoconidia and pseudohyphae.

On CMA, C. tropicalis produces smooth blastoconidia spores that are held by a hyphal stalk structure (mycelium). The spores are pigmented and septate.

On CCA, C. tropicalis produces colonies with a typical dark blue color. This medium allows for the differentiation of C. tropicalis from other Candida species based on the chromogenic reaction.

C. tropicalis has the following preferred growth conditions:

• Optimal temperature: 25–35 °C (77–95 °F)
• Optimal pH: 4.5–6.5
• Optimal oxygen: Aerobic or facultatively anaerobic

C. tropicalis thrives in sugar and fat media. It can also grow in other media such as potato dextrose agar, potato-glucose, potato-carrot, tomato juice, and lima bean media.

Candida tropicalis is a yeast species that can cause both superficial and invasive infections in humans, especially in immunocompromised hosts . It is one of the most common Candida species isolated from blood cultures and can cause candidemia, a life-threatening condition with high mortality rates . The pathogenesis of C. tropicalis involves several factors that enable it to colonize, adhere, invade, and evade the host immune system.

Colonization

C. tropicalis can colonize various sites of the human body, such as the skin, mucous membranes, gastrointestinal tract, and genitourinary tract . It can also survive in environmental niches, such as seawater, soil, plants, and animals. Colonization is facilitated by the ability of C. tropicalis to form biofilms, which are complex communities of microorganisms attached to a surface and embedded in a matrix of extracellular polymeric substances . Biofilms confer resistance to antifungal agents, host defenses, and environmental stresses . C. tropicalis is a strong biofilm producer and can form biofilms on various medical devices, such as catheters, prosthetic valves, and implants .

Adherence

Adherence is the first step of infection and involves the interaction of C. tropicalis with host cells or tissues . C. tropicalis can adhere to epithelial and endothelial cells by using different adhesins, such as Als (agglutinin-like sequence) proteins, Hwp (hyphal wall protein) proteins, Eap (extracellular adherence protein) proteins, and mannoproteins . These adhesins recognize specific receptors on the host cells, such as integrins, cadherins, lectins, and extracellular matrix components . Adherence allows C. tropicalis to resist mechanical removal and initiate tissue invasion .

Invasion

Invasion is the process by which C. tropicalis penetrates the host tissues and reaches the bloodstream or other organs . Invasion is mediated by two main mechanisms: active penetration and induced endocytosis . Active penetration involves the formation of hyphae, which are elongated filamentous cells that can exert mechanical pressure and secrete lytic enzymes to breach the host barriers . Induced endocytosis involves the uptake of C. tropicalis by host cells through phagocytosis or macropinocytosis, which can be triggered by fungal factors or host factors . Once inside the host cells, C. tropicalis can escape from the phagosomes or lysosomes and replicate in the cytoplasm or disseminate to other cells .

Evasion

Evasion is the ability of C. tropicalis to avoid or modulate the host immune response to establish and maintain infection . C. tropicalis can evade the host immunity by several strategies, such as:

• Phenotypic switching: This is a reversible change in colony morphology that can affect virulence attributes, such as adhesion, biofilm formation, drug resistance, and antigenicity .
• Morphogenesis: This is a transition between yeast and hyphal forms that can affect tissue invasion, immune recognition, and cytokine production .
• Secretion of immunomodulatory molecules: These include proteins (such as Sap (secreted aspartyl proteinase) proteins), lipids (such as phospholipases), polysaccharides (such as beta-glucans), and metabolites (such as farnesol) that can affect inflammation, phagocytosis, oxidative stress, apoptosis, and signaling pathways .
• Resistance to oxidative stress: This involves the production of antioxidant enzymes (such as catalase and superoxide dismutase) and molecules (such as glutathione) that can protect C. tropicalis from reactive oxygen species generated by the host cells.

These factors contribute to the pathogenicity of C. tropicalis and its ability to cause various clinical manifestations ranging from superficial infections (such as oral thrush and vulvovaginal candidiasis) to systemic infections (such as candidemia and disseminated candidiasis).

The most common mode of transmission of Candida tropicalis is the nosocomial transmission between health-care workers and patients . The fungi, which is predominantly found in immune-compromised patients with HIV/AIDS, cancer, leukemia, organ transplantation, causes a fungal infection known as candidiasis in various organ systems of the body . Candidiasis can affect the skin, mucous membranes, gastrointestinal tract, genitourinary tract, and bloodstream.

Candida tropicalis can also be transmitted through endogenous sources, such as the normal flora of the human host. The fungi can colonize the gastrointestinal tract and other mucosal surfaces and cause opportunistic infections when the host`s immunity is impaired or when the normal microbiota is disrupted by antibiotic therapy or other factors . Candida tropicalis can also invade the bloodstream from a primary site of infection, such as a catheter or a wound.

Another possible mode of transmission is through exogenous sources, such as the environment or contaminated materials. Candida tropicalis has been isolated from seawater, sea sediments, mudflats, marine fish intestine, mangrove plants, marine algae, shrimps, fruit surfaces, soil, and various foods . Therefore, it can be acquired through contact with these sources or ingestion of contaminated food or water.

The transmission of Candida tropicalis can be prevented by implementing infection control measures, such as hand hygiene, disinfection of medical devices and equipment, isolation of infected patients, and rational use of antibiotics and antifungals . Additionally, enhancing the host`s immunity and restoring the normal microbiota can help reduce the risk of candidiasis caused by Candida tropicalis.

Virulence factors are the characteristics of a microorganism that enable it to cause infection and disease in a host. Candida tropicalis has several virulence factors that contribute to its pathogenicity and clinical relevance. Some of the main virulence factors of C. tropicalis are:

• Adhesion: C. tropicalis can adhere to various surfaces, such as buccal epithelial cells, endothelial cells, medical devices, and dentures. Adhesion is mediated by cell surface molecules, such as mannoproteins, glycosylphosphatidylinositol (GPI)-anchored proteins, and hydrophobic proteins. Adhesion is crucial for colonization and biofilm formation, which are important steps for the establishment and persistence of infection .
• Biofilm formation: C. tropicalis can form biofilms on biotic and abiotic surfaces, such as mucosal tissues, catheters, prosthetic valves, and implants. Biofilms are complex communities of microorganisms embedded in a matrix of extracellular polymeric substances (EPS). Biofilms confer increased resistance to host immune responses and antifungal agents, as well as facilitate the dissemination of fungal cells into the bloodstream .
• Dimorphism: C. tropicalis can switch between yeast and hyphal forms in response to environmental cues, such as temperature, pH, serum, and nutrient availability. This phenomenon is also called morphogenesis or bud-to-hyphae transition. Hyphal forms are more invasive and virulent than yeast forms, as they can penetrate mucosal barriers and evade phagocytosis by host cells. Hyphal forms also secrete a toxin called candidalysin, which damages epithelial cells and facilitates fungal invasion into deeper tissues .
• Phenotypic switching: C. tropicalis can undergo phenotypic switching, which is the reversible change in colony morphology and expression of surface antigens. Phenotypic switching may affect the adhesion, biofilm formation, drug susceptibility, and immune recognition of C. tropicalis. Phenotypic switching may also generate phenotypic diversity and adaptation to different host niches .
• Secretion of hydrolytic enzymes: C. tropicalis can secrete various hydrolytic enzymes, such as proteases, phospholipases, lipases, and hemolysins. These enzymes degrade host tissues and cell membranes, facilitating fungal invasion and dissemination. They also modulate host immune responses by activating or inactivating cytokines, chemokines, complement components, and coagulation factors .
• Stress tolerance: C. tropicalis can tolerate various environmental stresses, such as high temperature, high osmolarity, low pH, oxidative stress, and antifungal agents. Stress tolerance is mediated by several mechanisms, such as heat shock proteins (HSPs), calcineurin signaling pathway, efflux pumps, ergosterol biosynthesis pathway, and oxidative stress response genes .

These virulence factors make C. tropicalis a formidable pathogen that can cause serious infections in immunocompromised and immunosuppressed patients. Therefore, understanding the molecular mechanisms and regulation of these virulence factors may provide new insights for the development of novel strategies for the prevention and treatment of C. tropicalis infections.

Infections caused by Candida tropicalis vary on the site of localization of the fungi. The various clinical manifestations include:

• Superficial and mucosal candidiasis: It is associated with oral thrush (oropharyngeal candidiasis), angular cheilitis, and vulvovaginal candidiasis. Oral thrush is characterized by white patches on the tongue and mouth cavity that can be scraped off. Angular cheilitis is the inflammation and cracking of the corners of the mouth. Vulvovaginal candidiasis is marked by intense itching, abnormal thin watery discharge, pain during intercourse, and redness and swelling of the external genital organs. Candida tropicalis can also cause superficial infections of the skin and nails (onychomycosis), interdigital candidiasis (between the fingers or toes), and diaper rash.
• Systemic candidiasis: It occurs when Candida tropicalis spreads to the bloodstream (candidemia) and affects internal organs such as the heart, brain, kidneys, liver, spleen, and eyes. It is a common healthcare-associated infection that can be life-threatening if not treated promptly. It is more common among people with weakened immune systems, such as those with cancer, leukemia, organ transplantation, HIV/AIDS, diabetes, or kidney failure . Symptoms of systemic candidiasis may include fever, chills, shock, organ failure, confusion, headache, vision loss, and skin lesions.
• Chronic disseminated candidiasis: It is a severe form of systemic candidiasis that affects mainly leukemic patients and those with secondary neutropenia (low white blood cell count). It causes persistent infection of the liver, spleen, and kidneys that can lead to organ damage and death.

To diagnose Candida tropicalis infections, various specimens can be collected depending on the site of infection, such as skin scrapings, oral and genital swabs, tissue biopsies, blood, cerebrospinal fluid (CSF), or urine. The following methods can be used to identify C. tropicalis from the specimens:

Microscopic Examination

• A 10% KOH wet mount can be prepared from skin scrapings or tissue biopsies and examined under a microscope for the presence of pseudohyphae, which are characteristic of C. tropicalis .
• Differential stains such as haematoxylin and eosin, periodic acid–Schiff and Gomori–Grocott methenamine silver stains can be used to detect fungal elements in tissue sections taken from biopsy or autopsy specimens.

Cultural Identification

• C. tropicalis can be cultured on Sabouraud dextrose agar or yeast extract agar, which produce cream-colored, dull, smooth colonies with the formation of small blastoconidial spores held by a hyphal stalk structure (mycelium) .
• C. tropicalis can also be cultured on CHROMagar Candida medium, which produces colonies with a typical dark blue color.
• Cornmeal agar can be used to observe the smooth blastoconidia spores and pseudohyphae of C. tropicalis under a microscope.

Biochemical Characterisation

• C. tropicalis can be differentiated from other Candida species by its ability to produce acetic acid from glucose fermentation.
• C. tropicalis can also utilize various sugars and produce inositol from carbon sources.
• C. tropicalis is positive for urease production, which distinguishes it from C. albicans and C. dubliniensis.

Molecular Detection

• Polymerase chain reaction (PCR) can be used to amplify and detect the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA) of C. tropicalis, which is specific for this species.
• Sequencing of the ITS-rDNA can also be used to confirm the identity of C. tropicalis by comparing it with reference sequences in databases.

Candida tropicalis infections are treated with antifungal agents that target the fungal cell wall or membrane. The choice of antifungal depends on the type and severity of the infection, the patient`s immune status, and the susceptibility of the isolate.

For superficial and mucosal candidiasis, such as oral thrush, vulvovaginal candidiasis, and skin and nail infections, topical antifungals are usually sufficient. These include creams, ointments, lozenges, or suppositories that contain nystatin, clotrimazole, miconazole, or ketoconazole.

For systemic candidiasis, such as candidemia, disseminated candidiasis, and chronic disseminated candidiasis, intravenous antifungals are required. The most commonly used antifungals are amphotericin B, echinocandins, and broad-spectrum triazoles .

Amphotericin B is a polyene antifungal that binds to ergosterol in the fungal membrane and causes leakage of cellular contents. It is effective against most Candida species, but it has serious side effects such as nephrotoxicity, infusion reactions, and electrolyte disturbances. Therefore, it is usually reserved for severe or refractory cases.

Echinocandins are a class of antifungals that inhibit the synthesis of beta-glucan in the fungal cell wall. They include caspofungin, micafungin, and anidulafungin. They have fungicidal activity against Candida species and have fewer side effects than amphotericin B. They are recommended as the first-line treatment for candidemia and invasive candidiasis in non-neutropenic patients.

Broad-spectrum triazoles are a class of antifungals that inhibit the enzyme lanosterol 14-alpha-demethylase in the fungal membrane, which is involved in ergosterol biosynthesis. They include fluconazole, voriconazole, posaconazole, and isavuconazole. They have fungistatic activity against Candida species and have good oral bioavailability. They are recommended as the first-line treatment for candidemia and invasive candidiasis in neutropenic patients and as an alternative or step-down therapy for non-neutropenic patients.

However, some Candida tropicalis isolates may develop resistance to antifungal agents over time. This may be due to mutations in the target enzymes or genes, overexpression of efflux pumps, or alterations in the cell wall or membrane composition. Resistance to fluconazole is especially common among C. tropicalis isolates and may limit its use for recurrent or persistent infections . Therefore, antifungal susceptibility testing is recommended for all C. tropicalis isolates to guide optimal therapy. Newer antifungals such as voriconazole and echinocandins may overcome some of the resistance mechanisms and offer better outcomes for C. tropicalis infections .

Candida tropicalis is usually susceptible to most antifungal agents, but resistance can develop over time or during treatment. Resistance to fluconazole, a commonly used azole antifungal drug, has been reported in several clinical isolates of C. tropicalis. Fluconazole resistance may be due to mutations in the ERG11 gene, which encodes the target enzyme of azoles, or in the UPC2 gene, which regulates the expression of ERG11 and other genes involved in ergosterol biosynthesis. Overexpression of these genes can reduce the susceptibility of C. tropicalis to azoles.

Resistance to amphotericin B, a polyene antifungal drug that binds to ergosterol and disrupts the fungal cell membrane, is uncommon in C. tropicalis, but a few strains have demonstrated a high level of resistance to this agent. The mechanism of amphotericin B resistance is not fully understood, but it may involve alterations in the cell membrane composition or permeability.

Resistance to echinocandins, a class of antifungal drugs that inhibit the synthesis of beta-glucan, a major component of the fungal cell wall, is particularly concerning because echinocandins are the preferred treatment for invasive candidiasis caused by C. tropicalis. Echinocandin resistance may be due to mutations in the FKS genes, which encode the subunits of the beta-glucan synthase complex, the target enzyme of echinocandins. Echinocandin resistance can also emerge during therapy, especially in patients with persistent or recurrent candidemia.

Patients with C. tropicalis infections that are resistant to both fluconazole and echinocandins have very few treatment options. The alternative treatment is amphotericin B, which can be toxic for patients who are already very sick. Resistance to multiple antifungal drugs can also reduce the survival rate of patients with candidemia and invasive candidiasis.

Therefore, it is important to monitor the antifungal susceptibility of C. tropicalis isolates and to use antifungal drugs judiciously and appropriately. Antifungal stewardship programs can help optimize the use of antifungal drugs and prevent the emergence and spread of antifungal resistance.

Candida tropicalis infections can be prevented and controlled by various measures, such as:

• Hygienic washing of hands to get rid of fungal spores on the hands to prevent the spread of the fungi.
• Washing infected surfaces using water and ethyls.
• Avoiding prolonged use of antibiotics, catheters, and antifungals that can disrupt the normal microbiota and increase the risk of candidiasis .
• Maintaining good oral hygiene and denture care to prevent oral thrush.
• Using barrier methods such as condoms during sexual intercourse to prevent transmission of genital candidiasis.
• Controlling blood sugar levels in diabetic patients to reduce the susceptibility to candiduria.
• Implementing infection control practices in healthcare settings to prevent nosocomial transmission of Candida tropicalis, especially the multidrug-resistant Candida auris.
• Using over-the-counter (OTC) antifungal dosage forms such as creams and gels for effective treatment of local candidiasis.
• Seeking prompt medical attention and antifungal therapy for invasive candidiasis, especially in immunocompromised patients .
• Following the recommended treatment guidelines based on the infecting species and antifungal susceptibility .
• Using probiotics and novel vaccines as an advanced approach for the prevention of candidiasis.

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