microbial pathogenesis exam 6

Fungi are .

Eukaryotes

FUNGI vs BACTERIA — CELL STRUCTURE

Fungi: EUKARYOTIC; Bacteria: PROKARYOTIC

FUNGI vs BACTERIA — SIZE (DIAMETER)

Fungi: > 5 μm; Bacteria: < 2 μm

FUNGI vs BACTERIA — CELL WALL COMPONENTS

Fungi: CHITIN/GLUCAN; Bacteria: PEPTIDOGLYCAN

FUNGI vs BACTERIA — CYTOPLASMIC MEMBRANE

Fungi: CONTAIN STEROLS; Bacteria: LACK STEROLS

FUNGI vs BACTERIA — ORGANELLES

Fungi: +; Bacteria: -

FUNGI vs BACTERIA — NUCLEAR MEMBRANE

Fungi: +; Bacteria: -

FUNGI vs BACTERIA — RIBOSOMES

Fungi: 80S (60S, 40S); Bacteria: 70S (50S, 30S)

FUNGI vs BACTERIA — REPRODUCTION

Fungi: SPORES and BUDDING; Bacteria: BINARY FISSION

The Kingdom Fungi includes some of the most important organisms both in terms of their and roles.

ecological and economic

More than species of fungi.

6 million

species associated with humans.

600+

Provide medicines – produce and other antibiotics.

penicillin

Where do you find fungi?

In the environment; In soil and on/in plants; On/in humans/animals

Normally fungal growth is well controlled by the .

immune system

Common opportunistic pathogens in , patients.

HIV, chemotherapy

Antibiotics that target the bacterial surface .

do not work

There is a cell wall made of and (not found in humans).

chitin and glucan

Mycology – study of .

fungi

Mycosis (mycoses) – caused by fungi.

disease(s)

Endemic mycoses: pathogens are restricted geographically and have the ability to cause serious systemic infection in individuals.

healthy

Opportunistic mycoses: cause life-threatening systemic disease in patients.

immunosuppressed

Pathogenic fungi have two forms in nature:

Yeasts and Molds

Monomorphic fungi:

only grow in one form

Dimorphic fungi:

occur in both mold and yeast forms; temperature-dependent dimorphism; nutrient-dependent dimorphism

Pathogenic yeasts reproduce by budding called .

blastospores

Elongated forms that resemble hyphae called .

pseudohyphae

Hyphae:

tubular, branching, multinucleated, filamentous elements

Two forms of hyphal growth:

Septate; Aseptate

Septate hyphae:

Hyphae that are septated have protoplasm that is interrupted by cross walls

Aseptate hyphae:

Hyphae that are nonseptate have protoplasm that is continuous and multinucleated

Mycelium:

Intertwined masses of hyphae

Molds grow as .

multicellular filamentous colonies on agar plate (or on food)

Mold hyphae diameter varies:

5 – 10 microns

Sporulation is the method of .

reproduction

Sexual reproductive (perfect) state of fungi is called .

teleomorph

Asexual reproductive (imperfect) state of fungi is called .

anamorph

Conidia:

Spores which are produced and shed from the hyphae

Asexual spores of pathogenic fungi include:

Arthrospores; Blastospores; Chlamydospores

Arthrospores:

produced by segmentation of hyphae

Blastospores:

produced by budding

Chlamydospores:

large, thick walled, formed by differentiation of hyphal elements

Chitin:

comprised of N-acetyl glucosamine residues

Glucan:

comprised of D-glucose residues

Plasma membrane doesn’t have cholesterol — Contains .

ergosterol

Ergosterol is a major target for anti-fungal drugs — binds ergosterol.

Amphotericin B

Ergosterol is a major target for anti-fungal drugs — inhibit ergosterol synthesis.

Azoles

Effective components for innate resistance to fungal infection:

Epithelial cell turnover (epithelial shedding); Desiccation; Fatty acids; Low pH; Bacterial flora

What increases susceptibility to fungal infections?

Alterations in the balance of the normal flora, antibiotics, or changes in nutrition allow fungi, such as Candida albicans, to proliferate

PRRs that recognize fungi:

TLR2: β (1,6)-glucan; TLR4: mannan; TLR9: chitin; Dectin-1: β (1,3)-glucan; Mel-Lec: Melanin

General fungal pathogenesis process (overview).

Fungal adhesion to tissue, replication; Increased replication and morphotypes trigger inflammatory response; Invasion through intercellular junctions induces damage response; Inflammatory cytokine production causes increased neutrophil recruitment

Neutrophil Swarming:

neutrophils rapidly coordinate migration towards sterile inflammation and infection, forming clusters or swarms

NETosis:

Extracellular traps (NETs) released into infected tissues

Monocytes in infection & immunity — Beneficial.

Phagocytize and kill conidia; Cytokine production to enhance fungicidal activity of neutrophils; Transport conidia to the lymph nodes and facilitate adaptive CD4+ T cell responses; Antigen presentation; Improve memory responses

Monocytes in infection & immunity — Harmful.

Reservoir of viable conidia (Trojan horse); Can aid in dissemination; Resists extracellular killing mechanisms, latency

Clinical types of fungal infections & disease.

Superficial; Cutaneous infections: Dermatophytosis; Subcutaneous infections; Systemic infections; Opportunistic fungal infections

Mycotoxicosis:

An intoxication due to ingestion of toxic metabolites that fungi produced in food products

Oct 2022: WHO declares on fungal pathogens.

public health alert

Cutaneous and surface infections – are treated with antifungal creams and powders.

local

Invasive infection – requires antifungal agent.

systemic

Candidemia with no obvious end-organ involvement – minimum of .

2 weeks

High risk patients may receive treatment.

prophylactic (preventive)

Fungi are eukaryotes – targets to develop drugs.

limited

Classes of antifungal drugs currently exist.

Allylamines; Azoles; Echinocandins; Polyenes; Pyrimidine inhibitors

Allylamines – .

inhibit ergosterol synthesis

Azoles – .

prevent ergosterol synthesis

Echinocandins – .

target the fungal cell wall

Polyenes – .

bind ergosterol and form pores in membranes

Polyenes: Bind ergosterol which causes .

altered membrane permeability, leakage of cell constituents, and cell death

Allylamines: Block synthesis.

ergosterol

Azoles: Block synthesis.

ergosterol

Echinocandins inhibit to block cell wall synthesis.

β-(1,3) glucan synthase

Echinocandins are for a small number of fungal pathogens and have toxicity.

Specific; Minimal

Flucytosine:

gets incorporated by fungi into DNA and inhibits replication and protein synthesis

Flucytosine — Resistance develops .

quickly

Several species of Lactobacillus have anti-Candida activity — Direct inhibition.

Compete for adhesion sites; Coaggregation molecules; Production of secondary metabolites; Acids; Hydrogen peroxide; Biosurfactants – prevents adhesion and biofilm

Several species of Lactobacillus have anti-Candida activity — Indirect inhibition.

Stimulation of the immune system of their host through T cell activation - production of IL-17, which is protective against C. albicans

Traditional subunit vaccine approaches target endemic mycoses, including , , , and .

Histoplasma, Coccidioides, Cryptococcus, Blastomyces

Recombinant heat shock protein 60 (HSP60):

Yeast cell wall protein

HSP60 vaccine works by priming a CD4+ effector response.

Th1

Viruses are (i.e., not composed of living cells).

acellular

They cannot and don’t produce .

replicate; energy

No , no .

ribosomes; metabolism

Components of viruses:

Nucleic acid; Capsid; Accessory proteins; Envelope

Nucleic acid can be or DNA or RNA.

single stranded; double stranded

Capsid:

protein, typically forms an ordered structure around the genetic material of the virus

Accessory proteins can include , , , or other proteins that share similarity to host proteins.

polymerases, proteases, endonucleases

Envelope – only present in viruses and is derived from the plasma membrane.

enveloped; host

Capsid symmetry:

Icosahedral; Helical

Enveloped viruses emerge from host cell by “”.

budding

Non-enveloped viruses emerge from cell by causing of host cells.

lysis

Viruses are classified based on their and history.

genetic material; evolutionary

Double stranded DNA viruses:

Tend to be large; Can use host polymerase to replicate; therefore, these viruses are often oncogenic

Single stranded DNA viruses:

must avoid cellular machinery that degrades SS DNA

Double stranded RNA viruses require to replicate.

viral polymerase

Plus (+) strand RNA viruses require to replicate.

viral polymerase

Minus (-) strand RNA viruses require to replicate.

viral polymerase

Retroviruses:

Integrate into host genome; Require viral reverse transcriptase to replicate

Viruses require host cells; they do not replicate .

living; extracellularly

Viral RNA polymerases have .

exceptionally high error rates