Fungal Pathogenesis De Carolis

Reproduction by spore formation.

The development of human mycoses is related primarily to the environmental exposure and immunological status of the host.

Primary fungi and opportunistic fungi.

Fungi can have a commensal relationship or cause an infection in their host.

The initial step involves the germination of conidia into mycelia.

The composition and relative abundance of fungal species are influenced by the body surface that is colonized and the health status of the individual.

Selection for mutations that increase fitness.

Fungi reproduce by spore formation.

C. neoformans has several virulence factors including a thick polysaccharide capsule, melanin production, and the ability to grow at 37°C, which helps it evade the host immune system.

Mucocutaneous mycoses are fungal infections that affect the mucous membranes and skin.

At 25 °C.

Circulating gliotoxin is readily detected in sera from patients with IA, while it is occasionally detected in patients without IA.

Rigid wall

Generally no, except for dermatophytes and mucocutaneous candida infections.

The transition of Candida albicans from yeast to hypha involves morphological changes that allow the organism to adapt to different environments, often associated with pathogenicity.

Candida produces proteinases, specifically secreted aspartyl proteinases (Saps), lipases, and phospholipases.

The capsule inhibits phagocytosis by professional phagocytes and resists phagosome digestion.

Pseudohyphae are formed through incomplete budding, where the cells remain connected after division.

It accumulates in vesicles within the cytoplasm of the host cell, leading to macrophage dysfunction and lysis.

Gliotoxin is responsible for slowing ciliary beating in the respiratory tract and for epithelial layer damage.

Onset of high fever, vomiting, convulsions, edema, and hemorrhaging.

Inhaled spores.

Dimorphism in pathogenic fungi.

High damage.

Yes, adhesion molecules can enhance the virulence of fungal pathogens by promoting adherence to host cells.

It allows them to adapt and successfully invade the host by switching growth forms.

Fungal hyphae.

They can grow into hyphae, which, if not killed, can invade tissue, the circulation, and disseminate.

Cryptococcus neoformans and Histoplasma capsulatum.

Hematopoietic stem cell transplant (first 30 days), Induction chemotherapy (haematological malignancies), Solid organ transplantation.

Examples include thermal dimorphism, adhesion factors, hydrolytic enzymes, toxin production, capsules, and inflammatory stimulants.

The enzymes cause damage to host cells and provide nutrients, allowing Candida to thrive in a restricted environment.

It is the ability to switch between two or more different growth forms, which is a key factor for certain species to successfully invade the host.

Eukaryotic

Intracellular pseudohypha formation refers to the ability of certain fungi to form elongated, filamentous structures within host cells, which can help them evade the immune response.

Elevated body temperature.

At 37 °C.

Cryptococcus neoformans typically causes cryptococcal meningitis, especially in individuals with weakened immune systems.

Subcutaneous mycoses are fungal infections that penetrate the skin and affect the underlying tissues.

A fungal infection caused by Zygomycetes, often affecting immunocompromised individuals.

Phagocytosis and inflammatory response.

Alveolar macrophages provide the first line of innate cellular defense by binding, internalizing, and killing the spores.

The immunological status of the host and environmental exposure.

It produces spores and is referred to as reproductive mycelium.

Gliotoxin can inhibit macrophage phagocytosis, T-cell activation, and proliferation, and can induce macrophage apoptosis.

Once adapted to a host, it allows for specialization.

Adhesion molecules are proteins located on the cell surface that facilitate cell-cell and cell-extracellular matrix interactions.

Cell-mediated immunity.

A biofilm is an aggregate of microorganisms in which the cells are stuck to each other and/or to a surface, forming complex surface-associated cell populations embedded in an Extracellular Matrix (ECM).

Unicellular or pluricellular

The clinical implications include increased difficulty in treating infections, particularly in immunocompromised patients, and the potential for persistent infections.

Virulence.

2 - 10 mm.

Biofilms provide protection from host defenses, making it more difficult for the immune system to eliminate the microorganisms.

Aspergillus flavus, Fusarium spp., and Penicillium spp.

Yeasts and molds.

The ability to survive and replicate at 37 °C.

Fungi are found on various body surfaces, and their composition and relative abundance depend on the surface colonized and the health status of the host.

The mycelial structure invades pulmonary epithelial and endothelial cells.

Low-virulence strains take longer for the mycelium-to-yeast phase transition at 37ºC, while more virulent strains withstand drastic temperature changes and transform more quickly.

The capsule and melanin.

Mycotoxins can affect the replication of DNA.

Biofilm formation in C. albicans is significant as it enhances its resistance to antifungal treatments and contributes to its pathogenicity.

Through contamination of the skin surface.

Fungi can escape from phagocytosis by various mechanisms, including altering their surface properties, producing capsules, or forming intracellular structures that resist degradation.

Dectin-1.

Fungal species have evolved mechanisms to survive in host cells and escape from phagocytosis.

Significant damage.

Deep mycoses are classified into primary and opportunistic infections.

Fungi are diverse organisms that can cause infections in humans, particularly in immunocompromised individuals. They can enter the body through various routes and adapt to host environments.

At the apex.

Without septa (zygomycetes).

Increased biofilm formation can lead to higher mortality rates due to the protective environment it provides for pathogens, making them more resistant to treatment.

Fungal adhesion, colonization, dissemination, ability to survive in the environment, and evasion of host immune response mechanisms.

It is in physical contact with the substrate, anchoring and absorbing nutrients.

Deterioration of liver and kidney function, skin necrosis, immunodeficiency, trembling, brain damage, and death.

Its ability to utilize catecholamines for melanin synthesis.

Dimorphism is linked to virulence, with more virulent strains exhibiting quicker transformation between mycelium and yeast forms.

Fungi can transition from an ovoid yeast form to a filamentous form, including hyphae and pseudohyphae.

Etherotrophic

It maintains the integrity of barriers.

Zygomycetes, Ascomycetes, Basidiomycetes, Chytridiomycetes, and Glomeromycetes.

Phagocytosis and inflammation.

Class 1 Opportunistic.

There are no specific signs or symptoms to distinguish them.

Planctonic cells and biofilm cells possess distinct phenotypes compared to their planktonic cell counterparts.

Fungi can alter their metabolic processes and form structures like hyphae to invade tissues and evade the immune response.

Fungi can alter their metabolic processes, evade the immune response, and reproduce rapidly to establish infections.

Over 300,000 species.

The N-terminal domains of Als protrude from the Candida cell wall and bind proteins on the surface of host cells, facilitating adhesion.

Spores are inhaled regularly and cleared without pathology.

A biofilm is a structured community of A. fumigatus cells embedded in a self-produced matrix, which can enhance its survival and resistance to antifungal treatments.

Pneumonia and meningo-encephalitis.

Induction of cancer (liver, oesophagus) and mutagenic and teratogenic toxicity.

It enables fungi to expand their environmental range, infect new hosts, evade the immune system, and adapt to antimicrobial therapy.

Adhesion molecules help fungi adhere to host tissues, which is crucial for colonization and infection.

These yeast cells can withstand antimicrobial activities, proliferate intracellularly, and escape from the host cell.

C. albicans yeast cells adhere to host cell surfaces through the expression of adhesins, and invasion is facilitated by adhesion and secretion of fungal hydrolases. Additionally, attachment to surfaces can lead to biofilm formation.

They aid in the movement to clear pathogens.

Sexual and asexual

Immunocompromised patients, with exceptions for true pathogens.

Mice infected with a non-gliotoxin-producing strain survive longer than those infected with a gliotoxin producer.

Biofilm infections hinder fungal eradication efforts, as the protective matrix of the biofilm shields the fungi from both the immune response and antifungal agents.

Risk factors include a weakened immune system, prolonged antibiotic use, diabetes, and certain medical conditions that compromise the body's defenses.

Fungi can enter the body through inhalation, skin contact, or ingestion, often exploiting breaks in the skin or mucosal barriers.

Fungi are diverse organisms that can cause infections in humans, particularly in immunocompromised individuals. They can enter the body through various routes and adapt to host environments.

A dense colony of filaments embedded in a polymeric extracellular matrix.

Fungi can evade the immune system by altering their surface antigens, producing immunosuppressive factors, and hiding within host cells.

Fungi are diverse organisms that can cause infections in humans, particularly in immunocompromised individuals. They can enter the body through various routes and adapt to host environments.

Thermal dimorphism, adhesion factors, capsules, hydrolytic enzymes, and toxin production.

Yeasts reproduce by multilateral budding, forming globose or elongate yeast-like cells known as blastoconidia.

Any chemotherapy, Critical illness, Mechanical ventilation, Central venous catheter, Hemodialysis, Total parenteral nutrition, Malnutrition, AIDS, Broad spectrum antibiotics, Diabetes, Intra-abdominal surgery.

Molds are pluricellular filamentous structures called hyphae that intertwine to form a tangled structure called mycelium.

Ingestion or inhalation of contaminated substances.

Superficial mycoses are fungal infections that affect the outer layers of the skin and hair.

In hosts with weak immune responses or normal immune responses.

Up to 93% of A. fumigatus strains from cancer patients with IA produce gliotoxin.

Biofilm infections can significantly reduce the effectiveness of antifungal treatments, making it more difficult to eradicate the fungi.

Biofilms enhance resistance to antimicrobial agents due to their complex structure and the protective nature of the Extracellular Matrix (ECM).

Toxic metabolites produced by certain molds that occur as contaminants of crops.

An infection caused by Candida species, commonly affecting mucosal surfaces and can become systemic in immunocompromised individuals.

Fungi are diverse organisms that can cause infections in humans, particularly in immunocompromised individuals. Understanding their biology and the conditions that lead to infections is crucial.

Risk factors include a weakened immune system, prolonged antibiotic use, diabetes, and certain medical conditions that compromise health.

Risk factors include a weakened immune system, prolonged use of antibiotics, diabetes, and invasive medical procedures.

Fungi can cause tissue damage through direct invasion, release of enzymes, and triggering inflammatory responses.

Fungi are divided into yeasts and molds (or filamentous fungi).

In the central nervous system, particularly in areas rich in these molecules like the basal ganglia.

Cell-mediated immunity, phagocytosis, and inflammation are the most important defenses.

Yeasts are unicellular and made by one eukaryotic cell, which can be rounded or elongate, typically measuring 3 - 5 mm.

C. albicans forms biofilms by adhering to surfaces, proliferating, and producing an extracellular matrix that protects the cells within.

Inoculated skin due to trauma.

The Extracellular Matrix (ECM) of a biofilm contains DNA, proteins, and polysaccharides.

A. fumigatus, B. dermatitidis, C. albicans, H. capsulatum, P. carinii.

It can lead to significant damage from various fungal pathogens.

A disease caused by the Aspergillus species, which can lead to respiratory issues, especially in immunocompromised patients.

Fungi are diverse organisms that can cause infections in humans, particularly in immunocompromised individuals. Understanding their biology and the conditions that lead to infections is crucial.

Aflatoxins, Fumonisins, and Ochratoxins.

Fungi can alter their morphology, utilize host nutrients, and evade immune responses to thrive and reproduce within the host.

Biofilm infections can lead to increased morbidity and mortality due to their resistance to treatment and the complications they cause.

Chitin (long-chain polymer of N-acetylglucosamine).

Class 3 Primary True Pathogens.

A serious fungal infection caused by Cryptococcus neoformans, primarily affecting the lungs and central nervous system.

Common risk factors include a weakened immune system, prolonged antibiotic use, diabetes, and invasive medical procedures.

Fungi can evade the immune system through various mechanisms, including altering their surface antigens and secreting enzymes that degrade immune components.

Septate (ascomycetes, basidiomycetes).

Fungi can enter the body through inhalation, skin contact, or ingestion, often exploiting breaks in the skin or mucous membranes.

Fungi can enter the body through inhalation, skin contact, or through mucous membranes.

Fungi can cause tissue damage through direct invasion, inflammation, and the release of toxic metabolites, leading to necrosis and organ dysfunction.

Fungi can cause tissue damage through direct invasion, inflammation, and the release of toxins.

Fungi can enter the body through inhalation, skin contact, or through mucosal surfaces, especially in individuals with compromised barriers.

Fungi can adapt by altering their morphology, utilizing host nutrients, and forming spores to propagate and spread within the host.

Fungi can cause tissue damage through direct invasion, release of enzymes that degrade host tissues, and triggering inflammatory responses.

They can have potential toxicity.

Coenocytic hyphae have no crosswalls.

Fungi can cause tissue damage through direct invasion, releasing enzymes that degrade host tissues, and triggering inflammatory responses.

Fungi can produce substances that inhibit immune responses or mimic host tissues to avoid detection.

Fungi can produce factors that inhibit immune responses, disguise themselves from immune cells, or modify their surface antigens.

Fungi can adapt by altering their morphology, utilizing host nutrients, and forming biofilms to resist immune responses.

It embeds and glues hyphae together and protects the fungus from an outside hostile environment.

Fungi can produce substances that inhibit immune responses, change their surface antigens, and form biofilms to protect themselves from immune detection.

Risk factors include immunosuppression, diabetes, prolonged antibiotic use, and invasive medical procedures.

Fungi can enter the body through inhalation, skin contact, or through mucosal surfaces.

900 million years

Aspergillus, Candida, Mucor, and Cryptococcus.

Aspergillus fumigatus is known for causing aspergillosis, particularly in immunocompromised individuals.

The loss of flagella is a significant evolutionary change.

Candida albicans is commonly associated with candidiasis, which can affect mucosal surfaces and cause systemic infections.

Chytrids are single-celled protists with flagella.

Chytrids were the earliest to diverge from protists.

Some major fungal pathogens include Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans.