medical mycology

Medical mycology
Mycology is the study of fungi . There are more than 50, 000 species of fungi , but most are beneficial to humankind .
Why Study the Fungi ?
• Fungi are an extremely important part of the ecosystem
– Recycling of minerals and carbon
– Source of food, medicines, and chemicals
– Important models in scientific research
– Cause plant and animal diseases
All fungi are eukaryotic organisms and each fungal cell has at least one nucleus .
Fungi grow in two basic forms , as yeast and molds . Growth in the mold form occurs by production of multicellular filamentous colonies called hyphae , varying in diameter from 2 ?m to 10 ?m . Some hyphae are divided into cells by cross – walls or septa .
Yeast are single cells , usually spherical to ellipsoid in shape and varying in diameter from 3 ?m to 15 ?m . Most yeasts reproduce by budding , then produces a chain of elongated yeast cells called pseudohyphae .
Fungal infections are mycosis . Most pathogenic fungi are exogenous ,their natural habitats being water , soil , and organic debris . The mycoses with the highest incidence – Candidiasis and dermatophytosis - are caused by fungi that are part of the normal microbial flora .
Oral fungal disease
Fungal infections in the oral occure either as primary localized lesions or as manifestication of systemic mycoses .The most common group of fungal infections that dental pracitioners diagnose and treat are caused by Candida spp.Some of the rarer mycoses such as histoplasmosis .
Candidiasis is a primary or secondary mycotic infection caused by members of the genus Candida , the clinical manifestations may be acute, sub- acute or chronic to episodic and involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract, or become systemic as in septicemia, endocarditic and meningitis .Systemic candidiasis is usually seen in patients with cell-mediated immune deficiency, and those receiving aggressive cancer treatment, immunosuppression, or transplantation therapy .
Clinical manifestations :
Thrush
It is an infection of mouth caused by Candida and the common sign of thrush is the presence of creamy white , slightly raised lesion of the mouth . The lesion , may have a "cottage cheese " appearance , in severe cases , may spread into the esophagus , or swallowing tube , causing pain or difficulty swallowing .
Stomatitis
Stomatitis is an inflammation of the mucus lining of any of the structures in the mouth which may involve the cheeks , gums , tongue , lips , throat .
Erythematous candidosis related to dentures is the most common form of oral candidosis in about 50 % of denture wearer .
Angualr cheilitis
Angular cheilitis is an inflammatory lesion at the labial commeasure , or corner of the mouth and often occurs bilaterally . However , nutritional deficiencies such as vitamin B12 and iron also some underlying causes for angular cheilitis . It also reported that angular cheilitis is one of the common presentations of oral candidiasis in HIV infected patients .
Candida albicans is the most common species isolated from the oral cavity in both healthy and diseased (in 60 - 80% of the cases . )
Other species responsible for oral infections have also been identified including C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, C. tropicalis, C. kefyr and C. guilliermondii . Also species such as C. inconspicua, C. lusitaniae, C. norvegensis and C. rugosa have been isolated occasionally from patients
Pathogenesis
The ability of Candida to adhere to the mucosa and dentures plays an important role in the pathogenesis of oral yeast infections . Adherence is achieved by specific and nonspecific mechanisms. However the mechanisms of are still not fully understood . Local defense mechanisms have a key role in preventing yeast colonization in the oral cavity. These include the physical local barrier of the epithelia, antimicrobial peptides, secretory immunoglobulin A, and salivary factors such as flow rate and specific . molecules (lysozyme, histatin and lactoferrin) . Secreted aspartic proteinase (SAP), phospholipases and lipases are extracellular enzymes that facilitate adherence and/or tissue penetration. SAPs efficiently
degrade extracellular matrix and host surface proteins (laminin, fibronectin, and mucin . )
Histopathology
The histological profile of C. albicans infections shows yeasts and pseudohyphae. C. glabrata, however, appears to produce only yeast forms . Histopathologic response is in most cases characterized as inflammatory or as an abscess .
Candida biofilms
Fungal biofilms and their role in infection and drug resistance have received increasing amounts of interest in the past years. There is already quite a lot of information about bacterial biofilms .
In the oral cavity yeast biofilms may form on acrylic dentures and dental implants .
Biofilms are structured microbial communities that are tightly attached to a surface and which are embedded within a matrix of extracellular polymers .
Studies on Candida biofilms have revealed that the formation of the biofilm begins with the attachment of the cells to each other. This is followed by the formation of germ tube and extracellular matrix. The third phase is the formation of hyphae and pseudohyphae by the yeast cells .
The mature biofilm has a three dimensional structure which may be several hundred microns deep . It is gel-like, highly hydrated and the micro-organisms in it are largely immobilized . C. dubliniensis biofilms have similar 3-D structures as C. albicans .
It consists of patches of mushroom-shaped biofilm communities rather than biphasic arrangement of discrete layers . Biofilms have reduced susceptibility to the host immune system, disinfectants, and drugs .
All of the commonly used antifungal agents have been reported to have a decreased activity against candidal biofilms
Examples risk patients for oral candidiasis
Patients with dental prostheses
Patients with reduced salivary flow rate
Patients with oral mucosal diseases
Asthmatic patients on corticosteroid therapy
Diabetic patients
Patients with rheumatic diseases
HIV infected and AIDS patients
Patients with malignant disease
Patients receiving immunosuppressive drugs
Patients receiving radiotherapy to the head and neck
The elderly
NCAC in oral mucosal lesions
Candida is commonly cultured from oral mucosal lesions. Candida has been reported to cause infection in 37% to 50% of oral lichen planus (OLP) cases . The treatment of OLP with steroids may lead to secondary yeast infection and may complicate the treatment of OLP. C. albicans, C. glabrata and C. tropicalis have been isolated from OLP lesions treated with topical steroids .
Oral leukoplakia is defined as a white patch or plaque that cannot be rubbed off or characterized clinically or pathologically as any other disease . Candidal hyphae are found in about 10% of all leukoplakias .
Identification of Candida
There are differences among the Candida species in the susceptibility to the different antifungal agents
available. Therefore identification of the species behind an infection is needed to ensure proper medication. CHROMagar is a medium that is widely used to identify C. albicans, C. krusei, and C..tropicalis. The medium contains chromogenic substrates which react with enzymes secreted by the target micro-organisms to yeald colonies of varying colours . C. albicans forms green colonies, C. tropicalis steel blue colonies, and C. krusei fuzzy, rose coloured colonies
Antifungal therapy :
Antifungal can be grouped into three classes based on their site of action: azoles ,
which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes , which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis .
Many different types of mechanisms contribute to the development of resistance to antifungal. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and over expression of the antifungal drug target
The first group, the Polyenes represented by amphotericin B, target ergosterol , a sterol present in the fungal cell membrane, and make pores causing cell death
The second group of antifungal drugs is ergosterol biosynthesis inhibitors,which
include azoles, morpholines and allylamines.They can inhibit the late pathway of ergosterol biosynthesis and cell division, causing loss of membrane structure and
function. Azoles are the most popular drugs from this group, and they can be divided into two classes: imidazoles, which include ketoconazole and
clotrimazole used for superficial infections, and triazoles, which include fluconazole, voriconazole and itraconazole used for systemic infections .
The third group includes inhibitors of nucleic acid synthesis, i.e. 5-flucytosine which is converted by to 5- fluorouracil(5-FU) by the enzyme cytosine deaminase , subsequently ,5-FU is converted by UMP pyrophosphorylase into 5- fluorouridylic acid , which is further phosohorylated and incorporated into RNA , resulting in disruption of protein synthesis .
A serious problem in treatment of fungal infections is the resistance to azoles and 5-flucytosine through a mechanism dependent on alternations in the target enzyme and in drug efflux pumps .