1. Medical Mycology

2. Basic characteristics of fungi

3. Fungi are not plants or animals
Unlike animals, most fungi are nonmotile and possess a rigid cell wall
Unlike plants, fungi are nonphotosynthetic

4. Role of fungi in nature
There are approximately 80,000 recognized species of fungi.
Most are beneficial to humankind.
food
production of food
antibiotics and immunosuppressive drugs
used as model systems in molecular biology

5. Medical Mycology the subject on pathogenic fungi
Some fungi act as the plant and animal pathogens in the agricultural industry.
About 300 species of fungi cause human infections.

6. Characteristics of fungi
Each fungal cell has at least one nucleus with a nuclear membrane, endoplasmic reticulum, mitochondria and secretory apparatus
Most fungi are aerobes
Fungi secrete enzymes that degrade organic substrates into soluble nutrients which are then absorbed into the cell
Fungi have rigid cell walls composed of glucans and chitins
Maybe haploid or diploid
Both sexual and asexual reproduction

7. Comparison of fungi and bacteria
Feature
Fungi
Bacteria
diameter
3-15 µm(yeast)
0.5-2 µm
nucleus
eukaryotic
prokaryotic
cytoplasm
with mitochondria and endoplasmic reticulum
without mitochondria and endoplasmic reticulum
Cell wall
chitin
peptidoglycan
spores
sexual and asexual spore for proliferation
spore for survival, not for proliferation
dimorphism
yes No
metabolism
Require organic carbon and no anaerobes
May not require organic carbon and maybe anaerobes

13. Cellular Morphology Yeasts: unicellular organisms Molds: multicellular
Dimorphic fungi: capable of growth as a yeast or mold depending on environmental conditions
Hypha，mycelium菌丝

14. Yeast Yeast are usually spherical to ellipsoid.
Most yeasts reproduce by budding.
Some produce buds that fail to detach and become elongated, producing a chain of elongated yeasts called pseudohyphae
A blastospore is an asexual fungal spore produced by budding

15. Mold
molds

16. a mold is multicellular microbes composed of two parts: spore and hypha.
Hyphae
spore

17. Hyphae
Hyphae: Tubular, branching fiaments (2–10 μm in width) of fungal cells, the mold form of growth. Most hyphal cells are separated by porous cross-walls or septa.
Mycelium: the mass of intertwined hyphae that accumulates during active growth.
Vegetative hyphae anchor the colony and absorb nutrients.
Aerial hyphae project above the colony and bear the reproductive structures.

18. Mycelium
Mycelium: the mass of intertwined hyphae that accumulates during active growth.

19. Spore
Spore: A specialized propagule with enhanced survival value, such as resistance to adverse conditions or structural features that promote dispersion.
Spores may results from asexual (e.g. conidia. sporangiospores) or sexual reproduction.
Most pathogenic fungi produce asexual spores.

20. Spores conidiophores thallospores sporangiospores macroconidia
microconidia
thallospores
blastoconidia/
blastospores
arthrospores
chlamydospores
sporangiospores

21. Conidium: asexual reproductive structures produced either from the transformation of a vegetative yeast or hyphal cell or from a specialized conidiogenous cell.
Sporangiospore: Asexual mitotic spores produced within an enclosed sporangium.
Sporangiospore
conidium

22. 镰刀菌的大分生孢子 着色真菌的小分生孢子 macroconidia of Epidermophyton
microconidia of Trichophyton
sporangiospores of mucor
毛癣菌的小分生孢子
chlamydospores of Candida albicans
macroconidia of Fusarium
microconidia of Dematiaceae
镰刀菌的大分生孢子
着色真菌的小分生孢子

23. hypha conidiophore phialide conidia septa
An environmental isolate of Penicillium

24. Dimorphic fungi
Some fungi exist in both yeast and mycelial forms. These fungi are called dimorphic fungi.
　　Yeast form: a parasitic or pathogenic form. This form is usually seen in tissue of patients. Can be cultured at 37 ℃. Conversion to yeast form appears to be essential for pathogenicity.
　　Mycelial form: a saprophytic form. This is the form existing in nature. Can be cultured at 25 ℃.

25. Culture & Colony morphology
Sabouraud agar
Optimal temperature ℃, 37 ℃ for certain pathogenic fungi.
Aerobic.
Sabouraud agar is used to culture fungi and has a low pH that inhibits the growth of most bacteria; it also contains the antibiotic gentamicin to specifically inhibit the growth of Gram-negative bacteria.

26. Unicellular fungi

27. Multicellular fungi

28. Resistance
Fungi have strong resistance to dryness, sunlight, UV light and many chemical agents, but much sensitive to heat. Usually can be killed be exposure to heat of 60°C for 1 hour.

29. Drugs
The antibiotics to treat fungal infectious diseases are quite different compared to those to cure bacterial infectious diseases: amphotericin B (两性霉素B), anticandine (制霉菌素), miconazole (咪康唑), ketoconazole (酮康唑) etc.

30. Fungal Infectious diseases

31. Major clinical manifestations of fungal diseases:
◇Hypersensitivity：an allergic reaction to molds and spores.
◇Mycotoxicosis: poisoning of human and animals by food contaminated with mycotoxins.
◇Infectious diseases: caused by exogenous pathogenic fungi or endogenous fungi (opportunistic infections).
◇Inducing tumors: Some mycotoxins can induce tumors (e.g., aflatoxin causes liver cancer) (黄曲霉素).
Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, most notably Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are toxic and among the most carcinogenic substances known.[1] After entering the body, aflatoxins may be metabolized by the liver to a reactive epoxide intermediate or be hydroxylated and become the less harmful aflatoxin M1.

32. C. Subcutaneous mycoses
In general, humans have a high level of innate immunity to fungi and most of the fungal infections are mild and self-limiting.
Fungal infections are classified according to where the infections take place:
A. Superficial mycoses
B. Cutaneous mycoses
C. Subcutaneous mycoses
D. Systemic mycoses (endemic fungi and opportunistic fungi)

33. Cryptococcus neoformans
曲霉菌
假丝酵母菌
表皮癣菌
小孢子癣菌
毛癣菌
Mucor
毛霉菌
Cryptococcus neoformans
新型隐球菌
皮炎芽生菌
荚膜组织胞浆菌
巴西副孢子菌

34. Superficial mycoses:
Infections are limited to the hair or the outermost layers of skin.

38. Tinea Nigra (also known as "superficial phaeohyphomycosis,"[1] and "Tinea nigra palmaris et plantar"[1] is a superficial fungal infection that causes dark brown to black painless patches on the soles of the hands and feet.[2]:311

40. B. Cutaneous mycoses:
Fungi invade the keratinized layers (角化层) of skin, hair and nails and the diseases are limited in these layers.
The fungi causing these diseases are termed dermatophytes (皮肤癣真菌). They are a group of about 40 related fungi.
The diseases are referred to as dermatophytoses or  tinea (癣病).
Dermatophytes are probably restricted to the nonviable skin because most are unable to grow at 37°C or in the presence of serum.

41. Dermatophytoses are among the most prevalent infections in the world.
Dermatophytes are classified as geophilic, zoophilic, or anthropophilic depending on whether their usual habitat is soil, animals, or humans.
Anthropophilic species cause the greatest number of human infections. They elicit relatively mild and chronic infections, produce few conidia in culture, and may be difficult to eradicate.
Geophilic and zoophilic dermatophytes, being less adapted to human hosts, produce more acute inflammatory infections that tend to resolve more quickly. Dermatophytes are acquired by contact with contaminated soil or with infected animals or humans.

43. All tinea are caused by members of three genera: Trichophyton (毛癣菌)
Epidermophyton (表皮癣菌)
Microsporum (小孢子癣菌)
Unlike the superficial mycoses, cellular immune responses may be evoked

44. common cutaneous mycoses:

46. Key concepts: superficial and cutaneous mycoses
1. Superficial and cutaneous mycoses are among the most common of all communicable diseases. 2. Most superficial and cutaneous fungal infections are caused by species of Malassezia, dermatophytes, or Candida. 3. The growth of dermatophytes is inhibited by serum and body temperature, and these fungi rarely become invasive. 4. Geophilic and zoophilic dermatophytes usually cause acute, inflammatory lesions that respond to topical treatment within weeks and rarely recur. 5. Anthropophilic dermatophytes usually cause relatively mild, chronic lesions that may require months or years of treatment and frequently recur.

47. C. Subcutaneous mycoses:
The infections involve the dermis, subcutaneous tissue, muscle and fascia.
筋膜 fascia

49. Subcutaneous mycoses
The fungi that cause subcutaneous mycoses normally reside in soil or on vegetation. They enter the skin or subcutaneous tissue by traumatic inoculation with contaminated material.
These mycoses are usually confined to the subcutaneous tissues, but in rare cases they become systemic and produce life-threatening disease.

50. Sporotrichosis
Sporotrichosis is a disease caused by the infection of the fungus Sporothrix schenckii. Because roses can spread the disease, it is one of a few diseases referred to as rose-thorn or rose-gardeners' disease.
S. schencki is naturally found in soil, hay, sphagnum moss, and plants. It enters through small cuts and abrasions in the skin.
Sporotrichosis progresses slowly - the first symptoms may appear 1 to 12 weeks (average 3 weeks) after the initial exposure to the fungus. Serious complications can also develop in patients who have a compromised immune system.

51. Sporotrichosis (also known as "Rose gardener's disease"[1]) is a disease caused by the infection of the fungus Sporothrix schenckii.[2] This fungal disease usually affects the skin, although other rare forms can affect the lungs, joints, bones, and even the brain. Because roses can spread the disease, it is one of a few diseases referred to as rose-thorn or rose-gardeners' disease.[3]
Because S. schencki is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers.[2] It enters through small cuts and abrasions in the skin to cause the infection. In case of sporotrichosis affecting the lungs, the fungal spores enter through the respiratory pathways. Sporotrichosis can also be acquired from handling cats with the disease; it is an occupational hazard for veterinarians.
Sporotrichosis progresses slowly - the first symptoms may appear 1 to 12 weeks (average 3 weeks) after the initial exposure to the fungus. Serious complications can also develop in patients who have a compromised immune system.

53. Chromoblastomycosis
Chromoblastomycosis (chromomycosis) is a subcutaneous mycotic infection that is usually caused by traumatic inoculation of any of the recognized fungal agents, which reside in soil and vegetation.
Detection of the sclerotic bodies is diagnostic of chromoblastomycosis regardless of the etiologic agent.

55. Eumycetoma
Eumycetoma is a chronic, specific, granulomatous, fungal disease.
It is also known as Madura foot.
This infection is endemic in Africa, India, and Central and South America.
Eumycetoma usually involves the subcutaneous tissue after a traumatic inoculation of the causative organism.
It may spread to involve the skin and the deep structures resulting in destruction, deformity and loss of function, very occasionally it could be fatal.

56. 足菌肿 Eumycetoma is a chronic, specific, granulomatous,[1] fungal disease.[2] It mainly affects the foot; and Mycetoma pedis is also known as Madura foot. This infection is endemic in Africa, India, and Central and South America.[ Eumycetoma usually involves the subcutaneous tissue after a traumatic inoculation of the causative organism.Tumefaction and formation of sinus tracts characterize mycetoma. The sinuses usually discharge purulent and seropurulent exudate containing grains. It may spread to involve the skin and the deep structures resulting in destruction, deformity and loss of function, very occasionally it could be fatal.

57. Key concepts: subcutaneous mycoses
1. Subcutaneous mycoses may be caused by dozens of environmental molds associated with vegetation and soil. 2. These infections are usually acquired when minor cuts or scratches introduce soil or plant debris containing the pathogenic fungus. The ensuing infections are frequently chronic but rarely spread to deeper tissues. 3. Sporothrix schenckii, the cause of sporotrichosis, is a dimorphic fungus that converts from hyphal growth to yeast cells within the host. 4. The diagnostic feature of chromoblastomycosis is the microscopic observation of brownish, spherical sclerotic bodies within the lesions. 6. The hallmark of a mycetoma is localized swelling and the formation of fistulae that contain hard granules composed of hyphae and inflammatory tissue.

58. D. Systemic mycoses:
Systemic mycoses are fungal infections affecting internal organs. the infections originate primarily from the lung and then spread to many other organs. They may be endemic or opportunistic
Endemic mycoses are caused by dimorphic fungal species that are ubiquitously present in the soil and environment of certain geographic regions.
Opportunistic mycoses are infections due to fungi with low inherent virulence that cause disease in people with weakened immune defenses.
We only focus on opportunistic mycoses.

59. Opportunistic mycoses
Patients with compromised host defenses are susceptible to ubiquitous fungi to which healthy people are exposed but usually resistant.
As members of the normal mammalian microbiota, Candida and related yeasts are endogenous opportunists.
Other opportunistic mycoses are caused by exogenous fungi that are globally present in soil, water, and air.
Candidiasis is the most prevalent systemic mycosis

60. Cryptococcus neoformans
Cryptococcus neoformans are environmental yeasts. Unlike other pathogenic fungi, these yeast cells possess large polysaccharide capsules Cryptococcus neoformans occurs worldwide in nature and is isolated readily from dry pigeon feces, as well as trees, soil, and other sites.

61. C. neoformans with capsule is negatively stained by India Ink

62. Cryptococcosis
Acute or chronic infections in the lung, bone and skin, and meningitis
Meningitis can last several months and are highly fatal
Cryptococcus neoformans occurs in immunocompetent persons but more often in patients with HIV/AIDS, hematogenous malignancies, and other immunosuppressive conditions.

63. Cryptococcosis The major clinical manifestation is chronic meningitis.
Cerebrospinal fluid pressure and protein may be increased and the cell count elevate.
Patients may complain of headache, neck stiffness, and disorientation. There may be lesions in skin, lungs, or other organs.
The course of cryptococcal meningitis may fluctuate over long periods, but all untreated cases are ultimately fatal.
Globally, about 58% of patients with AIDS develop cryptococcal meningitis.

64. Transmission No human to human transmission.
Infection follows inhalation of pigeon or chicken droppings containing the microbe

65. Candida albicans
Candida albicans can be found in 40-80% of normal human beings. It is present in mouth, intestine and vagina.
Candida albicans is dimorphic fungus.
Candida albicans can show germ tubes (an outgrowth produced by spores of spore-releasing fungi during germination) with special shape, which used as a diagnostic feature of the microbe.
Candida albicans can cause both cutaneous and mucosal candidiasis and systemic candidiasis

66. Hypha formed during germination

67. Pseudohyphae and hyphae of Candida albicans using Methenamine Silver Stain.

68. Oral thrush is a typical and common disease caused by Candida albicans
鹅口疮
Oral thrush is a typical and common disease caused by Candida albicans

69. Key concepts: opportunistic mycoses
1. Opportunistic mycoses are caused by globally distributed fungi that are either members of the human microbiota or environmental yeasts and molds.
2. Innate host defenses provide crucial protection from systemic candidiasis.
3. Most patients with HIV/AIDS develop mucosal candidiasis. Those with CD4 counts less than 100 cells/μL are at risk for cryptococcosis, endemic mycoses, and other infections. 4. Successful management of opportunistic mycoses involves early diagnosis, rapid administration of appropriate antifungal therapy, and control of the underlying condition or disease