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BOT 306 > Human Pathogens and Antifungal drugs > Flashcards

Human Pathogens and Antifungal drugs Flashcards

1
Q

What are some immune evasion virulence factors?

A

Masking of PAMPs using capsules or pigments
Escape from immune cells

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2
Q

What are some robustness/stress resistance virulence factors?

A

Cell wall
Detoxification

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3
Q

What are some morphological transition virulence factors?

A

Yeast to hypha
Spore to yeast
Spore to hypha

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4
Q

What are some growth in host virulence factors?

A

37 degrees
Host derived nutrients
Adaptation to niches

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5
Q

What are some adhesion/invasion virulence factors?

A

Biofilm formation
Translocation

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6
Q

What are some damage virulence factors?

A

Physical forces
Secreted enzymes
Toxins

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7
Q

What are the prerequisites for life in or on humans?

A

The ability to grow well at 37 degrees

The ability to utilize many different carbon and nitrogen sources, and to scavenge for limiting elements

The ability to recognize and adapt to the conditions within the human host, which are very different from those outside

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8
Q

What happened after the asteroid hit Earth?

A

Fungi took over, need to decompose all of that dead matter

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9
Q

What do superficial/cutaneous mycoses affect?

A

Affects skin, hair, and nails

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10
Q

What do subcutaneous mycoses affect?

A

Affects muscle and connective tissue immediately below the skin; mainly tropical

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11
Q

What do systemic (invasive) mycoses affect?

A

Involves internal organs
Primary vs. opportunistic

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12
Q

What do allergic mycoses affect?

A

Affects lungs or sinuses
Patients may develop chronic conditions

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13
Q

What is a Malassezia infection?

A

Superficial/cutaneous
Can induce skin inflammation
Is the cause of dandruff
Obligate lipophile: colonizers around sebaceous glands

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14
Q

When does the maximum density of Malassezia occur?

A

Between the late teens and early middle age

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15
Q

Where do species utilizing keratin colonize and what do they cause?

A

Colonize hair, nails, and skin

Cause tinea (ringworm), tinea pedis (athlete’s foot), and toenail infection

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16
Q

Where do dermatophytes derive from?

A

Ascomycetes, specifically the order Onygenales in the class Eurotiomycetes

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17
Q

Candida is found in what percent of people?

A

Found in 40-60% of healthy adults and is one of the most common human-associated fungi

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18
Q

What is a candida infection?

A

Superficial/cutaneous

An ascomycete of the class Saccharomycetes

Infections are formed mostly by the yeast stage

Is the primary cause of candidiasis and thrush

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19
Q

What can cause serious Candida infections?

A

Antibiotic therapy and immunodeficiency

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20
Q

What do subcutaneous infections include and what fungi primarily cause them?

A

Include a variety of mycoses that develop in muscle and connective tissue

Mostly ascomycetes

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21
Q

What is Sporthrix?

A

A fungi that causes the subcutaneous infection sporotrichosis that is mostly acquired by traumatic injury

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22
Q

What other fungi can cause subcutaneous infections?

A

Zygomycetes
Dark hyphal fungi
Onygenales

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23
Q

What is a primary, systemic infection?

A

True fungal pathogens that can overcome the physiological and cellular defenses of the normal human host by changing their morphological form

Tend to be geographically restricted

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24
Q

Primary systemic fungal infections are mostly what?

A

Dimorphic

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25
Q

Who can primary systemic fungi infect?

A

Healthy individuals; cultures represent a severe biohazard to laboratory personnel and must be handled with extreme caution in an appropriate pathogen-handling cabinet

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26
Q

What is the primary site of infection of a primary systemic fungi?

A

Usually pulmonary, following the inhalation of conidia

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27
Q

Which two genera may require up to containment level 3?

A

Cryptococcus
Histoplasma

28
Q

What is histoplasmosis?

A

Systemic infection

Derived from bat or bird excrement

Symptoms may mimic those of TB

Symptoms are similar to blastomycosis

29
Q

What is blastomycosis?

A

Systemic infection

May originate from soil

Begins as asymptomatic pulmonary lesions and spreads to skin and bones

Can infect pets, jumps from pets to human

Common in subsistence communities in which hunting and fishing are daily activities

30
Q

Where is the blastomycosis incidence high?

A

In the Kenora region

31
Q

What is coccidiomycosis?

A

Systemic infection

Infects human lungs in dust storms

Forms large spherules which form endospores that spread the fungus further in the lungs and tissue

Can spread to the adrenal glands, bones, CNS, joints, lymph nodes and skin, and can be fatal

32
Q

What are the two phases of the coccidioides life cycle?

A

Parasitic and saprobic

33
Q

What is paracoccidioidomycosis?

A

Systemic infection

Infection through inhalation; widespread asymptomatic exposure but rare form can be lethal in juveniles

Most cases are men between 30-50 years old

Dimorphic switch from mycelium/conidium to yeast inhibited by physiological concentrations of the female sex hormone estradiol

Contains a high-affinity binding protein with similar properties to mammalian receptor proteins responding to steroid hormones

34
Q

What are the differences between yeast and hyphal cell wall in paracoccidioides?

A

hyphae = beta 1-3-glycan is the major component

yeast = alpha 1-3-glucan is the major component

35
Q

Blastomycosis and paracoccidioidomycosis are what type of disease?

A

Granulomatous diseases that can lead to extreme deformation of skin and facial features

36
Q

What are opportunistic systemic infections?

A

Infections of the body which occur almost exclusively in debilitated patients whose normal defense mechanisms are impaired

Caused by cosmopolitan fungi which have a very low inherent virulence

37
Q

What is aspergillosis?

A

Caused mostly by A. fumigatus

Abundant in compost, hay, and straw

Would lead to respiratory infections in people working with hay in confined spaces

Now it is one of the most frequently acquired nosocomial infections following immunosuppressive therapy

38
Q

What is allergic bronchopulmonary aspergillosis?

A

Leads to asthmatic reactions in asthma and cystic fibrosis patients

39
Q

What is pulmonary aspergilloma?

A

Forms balls of hyphae with host cells in the lungs

40
Q

What is invasive aspergillosis?

A

Spreads from the respiratory tract through blood vessels into other organs, especially the brain

41
Q

What is opportunistic candidiasis?

A

Same as the cutaneous form, but in immunocompromised patients it can enter the bloodstream

4th most common nosocomial infection

High mortality rate

42
Q

What are some Candida virulence factors?

A

Ability to adhere to host tissue

Produces adhesins that bind to a range of host proteins

Possesses an arsenal of extracellular enzymes that break down host proteins, including antibodies, lipases, and phospholipase

Ability to switch between yeast, hyphae, and pseudohyphae

Can form diploids and triploids

43
Q

What is cryptococcosis?

A

Opportunistic systemic infection

Through the inhalation of spores

Mostly latent or harmless, but in immunocompromised patients it can enter the bloodstream and cause meningoencephalitis

Melanin and the thick, acidic, mucopolysaccharide capsule of the yeast inhibits phagocytosis

44
Q

What is pneumocystosis?

A

Opportunistic systemic infection

Passed from human to human in close proximity

Causes pneumonia in premature babies, malnourished infants, and immunocompromised patients

Contains cholesterol, not ergosterol, in the PM

Previously thought to be a protest

45
Q

What is zygomycosis?

A

Opportunistic systemic infection

One of the most acute and destructive fungal infections known

Typically involves the rhino-facial-cranial area, lungs, GI tract, skin, or less commonly other organ systems

46
Q

How can fungal allergic reactions be mediated?

A

IgE-mediated hypersensitivity
IgG-mediated hypersensitivity
Immune complex-mediated hypersensitivity
Cell-mediated hypersensitivity

47
Q

What are 3 targets for antifungal therapy?

A

Plasma membrane = fungi mainly use ergosterol instead of cholesterol

DNA synthesis = some compounds may be selectively activated by fungi, arresting DNA synthesis

Cell wall = mammals do not have a polysaccharide-based cell wall

48
Q

What are azole antifungals?

A

A large group of synthetic agents, which includes drugs used in bacterial and parasitic as well as fungal infections

The majority are used as a topical treatment

Widely used because of their broad therapeutic window, wide spectrum of activity, and low toxicity

49
Q

Why are the Azoles a good line of defense?

A

They are good for most fungi and they are easily synthesized

50
Q

How do azoles disrupt ergosterol synthesis?

A

In fungi, cytochrome P450 enzyme lanosterol 14-alpha demethylase is responsible for the conversion of lanosterol to ergosterol

Azoles bind to Erg11 inhibiting the production of ergosterol

51
Q

How do Azoles act?

A

Through an unhindered nitrogen, which binds to the iron atom of the heme, preventing the activation of oxygen which is necessary of the demethylation of lanosterol

52
Q

How do Azoles work?

A

They inhibit the fungal P450 enzymes reponsible for the synthesis of ergosterol

The resulting depletion of ergosterol alters the fluidity of the membrane and this interferes with the action of the membrane-associated enzymes

53
Q

What is the overall effect of Azoles?

A

Inhibition of growth

54
Q

How do polyene antibiotics disrupt existing ergosterol?

A

Binds sterols in fungal plasma membrane

Binding interferes with permeability and transport functions, forms a pore in the membrane

Repercussion = loss of intracellular K, Mg, sugars, and metabolites and then cell death due to electrolyte leakage

55
Q

Which fungi are polyene antibiotics active against?

A

Most except for Aspergillus terreus and Scedosporium

56
Q

What are some issues with Amphotericin B?

A

The metabolic fate is unknown, only 2-5% appear in the urine
Children tolerate it better than adults

57
Q

What does flucytosine do to fungi?

A

It interferes with RNA and DNA synthesis by introducing a fluorouracil precursor to uridine triphosphate

It is introduced via a fungal-specific uptake mechanism so it doesn’t cross-react with mammalian RNA

58
Q

What is the first reaction with flucytosine?

A

5-FC to 5-FU via cytosine deaminase

59
Q

What is the second reaction with flucytosine?

A

Inhibition of thymidylate synthase = no dTMP, no DNA

Fluorine inhibits the synthesis of dTMP = no T in DNA

Incorporation into RNA, but F inhibits translation

60
Q

What is flucytosine active against?

A

A limited range of fungal infections, mainly candida and cryptococcus

61
Q

What is an issue with flucytosine?

A

Rapid resistance when it is used alone due to decreased permease (uptake) activity and altered 5-FC metabolism

62
Q

What is flucytosine often used with?

A

AmB

63
Q

What are echinocandins?

A

Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of beta 1-3 D-glucan synthase

Glucan synthases are absent from mammalian tissues

Loss of cell wall glucan results in osmotic fragility

64
Q

What do echinocandins contribute to?

A

Cell lysis at growing tips

65
Q

What is echinocandin’s activity spectrum?

A

Candida
Pneumocystis
Aspergillus, but no fusarium
Not cryptococcus neoformans

BOT 306 (16 decks)

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