Gram + pathogens (non spore vs spore) and toxins

Exam 3- Lecture 1

Describe the gram stain and morphology of Listeria monocytogenes

gram + rod, coccobacilli in pairs (short chains)

Identifying growth characteristics of listeria monocytogenes

grows at low temp (40 degrees celcisus), wide pH, high slat

Describe the gram stain and morphology of corynebacterium diptheria

gram + rod, non spore forming, in clumps

oxygen requirements of corynebacterium diphtheria

facultative anaerobe

Describe the gram stain and morphology of Bacillus

gram + rod, endospore forming (chains)

oxygen requirements for Bacillus

aerobic or facultative anaerobe

Describe the gram stain and morphology for Clostridium/Clostridioides

gram + rods, endospore forming(chains, often in pairs)

oxygen requirements for Clostridium

obligate anaerobic

How does listeria monocytogenes attach to enter host cells?

(bacterial proteins) bind to cell glycoproteins (cadherin), leading to internalization into M-cells and macrophages

Key virulence factors for Listeria to escape phagosome

Cytolysin (listeriolysin O) and Bacterial Phospholipase C which breaks down phospholipids

How does listeria monocytogenes spread within and btwn host cells?

ActA protein attaches to the bacterial cell and causes extension of actin filaments, which propels the bacteria out of the cell and into adjacent cells. Bacteria can also survive in migratory phagocytic cells to spread systemically

What are the common sources where listeria monocytogenes is found?

Consumption of infected foods, including milk, cheese, ice cream, and peanut butter. (Its ability to grow at low temperatures (4°C) contributes to foodborne outbreaks)

What are the common disease pathologies associated with listeria monocytogenes?

Gastroenteritis, meningitis, in utero disease

What are the sources of infection for corynebacterium diphtheria?

transferred by respiratory droplets, tDap, oropharynx carriage

Describe the disease pathology for Corynebacterium diphtheria

presents as respiratory (exudative) pharyngitis with malaise, sore throat, fever, swollen lymph nodes, and a characteristic pseudo-membrane. The secreted Diphtheria AB toxin can cause life-threatening systemic pathology, including myocarditis, polyneuropathy, paralysis, and kidney failure. (Cutaneous forms also exist)

What are the key virulence factors for listeria monocytogenes?

Internalins (for attachment), Listeriolysin O and Bacterial Phospholipase C (phagosome lysis), ActA protein (spread)

Describe the toxin produced by corynebacterium

secretes extremely toxic AB exotoxin (diphtheria toxin)

mechanism of AB exotoxin

B portion binds to (HB-EGF) receptor on host cells, and A portion enter and terminates host cell protein syn.

What are the major virulence factors of Bacillus anthracis?

Protein capsule (anti-phagocytic), Lethal factor, Edema factor, Protective antigen. (LF anf EF are A components, and PA is the common B component of Anthrax toxin) (PA+EF=edema toxin and PA+LF=lethal toxin)

What are the key virulence factors of bacillus cereus food poisoning?

enterotoxins, heat stable toxin=vomiting, and heat liable toxin that stimulates cAMP production= diarrhea

Important toxin produced by Clostridium perfringens

Alpha toxin (lecithinase=cells lysis), Beta toxin (necrotizing enteritis), Epsilon toxin (increase vascular permeability), Iota toxin (necrotic activity), and Enterotoxin (CPE=food poisoning/membrane permeability)

Describe toxins produced by Clostridium difficile and their effects

Enterotoxin(toxin A)- chemotactic for neutrophils and disrupts cell-to-cell tight junctions=increased permeability and water loss

Cytotoxin(toxin B)-causes actin depolymerization=destroying the cell cytoskeleton

What toxin is produced by Clostridium tetani?

Tetanospasmin- heat liable neurotoxin

Mechanism for Tetanospasmin

A fragment acts as a zinc endopeptidase that decreases the release of the inhibitory neurotransmitters GABA and glycine, leading to persistent excitatory stimulation

What is the toxin produced by clostridium botulinum?

AB toxin- inactivates proteins regulating acH release and nm junction = flaccid paralysis (BOTOX)

Where does Bacillus anthracis come from and how are humans exposed?

Herbivores (cows) with spores found in soil, humans infected by contact with contaminated animals/animal products (hides/wool) via inoculation (skin wounds), ingestion, or inhalation of spores.

Where does Bacillus cereus come from and how does food poisoning happen?

soil and GRAINS, food poisoning originates form spores contaminating rice and other grains, that survive cooking and produce toxins

Where does Clostridium come from?

soil (in the envrn) and spores are resistant to killing

How does Clostridium perfringes cause disease?

Spores can be introduced into closed wounds leading to gas gangrene. Food poisoning occurs from ingesting contaminated food where spores germinate post-cooking and produce enterotoxin. found in soil and water contaminated with feces

Where is C Diff found, and how does infection occur?

normal flora sometimes, disease occurs after long term antibiotic use bc it disrupts the normal gut microbiota.

Where does Clostridium botulinum come from and how does infection occur? botulism

soil, exposure comes form consumption of wrongly preserved cans (food borne), ingestion of spores by infants (soil, dust, honey), contamination of wounds, or inhalation of spores.

Where does Clostridium tetani come from and how does infection occur?

soil organism. Infection is usually introduced through puncture wounds or other closed wounds that allow the anaerobic environment needed

Listeriolysin O and Phospholipase C (listeria)

Facilitate phagosome escape, enabling intracellular survival spread- gastroenteritis, meningitis, and systemic infection.

ActA (listeria)

enables cell-to-cell spread, further contributing the systemic disease

How does diphtheria toxin lead to symptoms of diphtheria?

Diphtheria AB toxin inhibits host cells protein syn. which causes cell death in oropharynx and pseudo-membrane formation. Damages various organs= myocarditis, polyneuropathy, paralysis, and kidney failure.

How do to toxins of bacillus anthracis make diff forms of anthrax?

Edema toxin-increase cAMP causing edema in cutaneous and inhalation antrhax

Lethal toxin- disrupts MAP kinase signaling contributing to shock and death in systemic anthrax (inhalation)

capsule- protects against phagocytosis aiding in systemic spread

C.perfringens Alpha toxin

lyses leukocytes, RBCS, platelets, endothelial cella = hemolysis, vascular permeability, bleeding, tissue destruction and hepatic toxicity in gas gangrene

C. perfringens Enterotoxin (CPE)

disrupts membrane permeability of intestinal cells, causing fluid loss and watery diarrhea in food poisoning

How do the toxins of Clostridioides difficile causes symptoms of C.Diff

Toxin (A) enterotoxin- increases intestinal wall permeability leading to extensive water loss and diarrhea. (inflammation)

Toxin (B) cytotoxin- destroys the cell cytoskeleton, further damaging the intestinal lining

How does tetanospasmin cause spastic paralysis in tetanus?

it blocks the release of the inhibitory neurotransmitters GABA and glycine in the CNS, this results in continuous excitatory signals (continuous contraction) to muscles leads to spastic paralysis.

How does Botulinum toxin cause flaccid paralysis?

it blocks the release of acH at neuromuscular junction (signal for muscle contraction), leads to muscle weakness and flaccid paralysis.

Compare MOA for tetanospasmin and botox:

Tetanospasmin blocks release of inhibitory neurotransmitters (GABA and glycine in CNS), leads to overstimulation of muscles and spastic paralysis.

Botox blocks the release of excitatory neurotransmitter acH at the neuromuscular junction, preventing muscle contraction and flaccid paralysis.

What is the physiological outcome of tetanospasmin activity?

spastic paralysis due to the inability to inhibit muscle contraction

What is the physiological outcome of botox activity?

Flaccid paralysis due to the inability to stimulate muscle contraction