Gram Positive Pathogens: Clostridium, Mycoplasma, Bacillus, and Streptococcus

Gram Positive Pathogens

Introduction

  • The lecture focuses on gram-positive pathogens.
  • The next lecture will cover gram-negative pathogens.

Clostridium

  • Genus Clostridium, along with Bacillus, are endospore-forming bacteria.
  • Both are anaerobic bacilli (rod-shaped).
  • They are ubiquitous, found in soil, water, and animal gastrointestinal tracts.
  • Endospores allow survival under harsh conditions (heat, chemicals, UV, antibiotics).
Clostridium botulinum
  • Anaerobic, endospore-forming bacillus common in soil and water.
  • Botulism results from endospores germinating and producing botulism toxins.
  • Vegetative cells are actively growing and dividing.
  • Sporulation: cells form a septum and a secondary cell wall around themselves, and the mother cell dies, leaving the endospore.
  • Botox is derived from botulism toxin.
  • C. botulinum strains produce seven different toxins; among the deadliest known.
  • A teaspoon of botulism toxin could wipe out the Earth's population.
  • Botox uses nanogram quantities of the toxin.
  • Botox is also used to treat migraines and MS.
Mechanism of botulism toxin
  • Muscles are innervated by motor neurons connecting the central nervous system to effectors.
  • Sensory neurons sense stimuli (e.g., heat) and send signals to the central nervous system, which responds via motor neurons.
  • Motor neurons connect to muscle cells via the neuromuscular junction.
  • A synaptic cleft exists between the neuron terminus and the muscle cell.
  • Action potential causes vesicles filled with acetylcholine to fuse with the synaptic terminal membrane.
  • Acetylcholine diffuses across the synaptic cleft, binds to receptors on muscle cells, and causes muscle contraction.
  • Acetylcholine is either degraded by acetylcholinesterase or re-endocytosed back into the synaptic knob.
  • Botulism toxin binds to the neuron and prevents acetylcholine vesicles from exocytosing their contents and binding to receptors at the neuromuscular junction, which results in muscle paralysis because there's no signal from the central nervous system telling muscles to recoil.
Epidemiology and Diseases
  • Botulism is an intoxication with three manifestations:
    • Foodborne botulism: Death can result from asphyxiation due to paralysis of the diaphragm.
      • Recovery is slow, involving the growth of new nerve cell endings.
    • Infant botulism: Results from ingesting endospores (e.g., from honey).
      • Infants lack natural immunity to C. botulinum.
    • Wound botulism: Endospores enter a wound, with symptoms similar to foodborne botulism.
Diagnosis, Treatment, and Prevention
  • Symptoms are diagnostic.
  • Treatment includes:
    • Intestinal tract washing to remove Clostridium.
    • Administering neutralizing antibodies against botulism toxin, preventing the toxin's attachment to receptors (neutralization).
    • Administering antimicrobial drugs in infant and wound botulism cases because C. botulinum is gram positive.
  • Prevention includes:
    • Proper canning of food.
    • Avoiding feeding honey to infants under one year old.
Clostridium tetani
  • Causes tetanus, where muscles are always in a state of contraction, opposite of botulism toxin.
  • Motile, obligately anaerobic bacillus with a terminal endospore.
  • Ubiquitous in soil, dust, and GI tracts of animals and humans.
  • Tetanus results when endospores germinate and produce tetanus toxin (tetanospasmin).
Pathogenesis
  • Tetanospasmin is a potent neurotoxin that causes continuous muscle contractions.
  • Released by C. tetani cells when they die.
  • Normal muscle action involves stimulatory and inhibitory neurotransmitters.
    • Stimulatory neurotransmitters stimulate motor neurons to contract muscles.
    • Inhibitory neurotransmitters counteract the effect of stimulatory neurotransmitters.
  • Tetanospasmin blocks the release of inhibitory neurotransmitters, leading to constant muscle contraction.
Disease and Epidemiology
  • Begins with tightening of jaw and neck muscles (lockjaw).
  • Spasms and contractions can spread to other muscles.
  • Unrelenting contraction of the diaphragm can cause death.
  • Most cases occur in less developed countries due to inadequate medical care and lack of vaccination.
  • Recovery requires growth of new inhibitory neuronal terminals.
  • Has about a 50% death rate.

Mycoplasmas

  • Smallest free-living microbes; resemble fried eggs on a plate.
  • Lack cytochromes, Krebs cycle enzymes, and cell walls.
  • Most have sterols in their cytoplasmic membranes for rigidity.
  • Require growth factors from a host or laboratory media.
  • Colonize mucous membranes of the respiratory and urinary tracts.
  • Few species cause significant human diseases.
Mycoplasma pneumoniae
  • Attaches to epithelial cells lining the human respiratory tract.
  • Affects mucociliary transport and goblet cells, impairing the ability to clear pathogens.
  • Causes primary atypical pneumonia.
  • Symptoms aren't typical of other pneumonias and are not usually severe enough to require hospitalization.
  • Spread by nasal secretions among people in close contact.
  • Common in children 5-15 years old.
Diagnosis, Treatment, and Prevention
  • Small and difficult to detect.
  • Grow very slowly in culture and in humans (dividing over weeks).
  • Macrolides treatment is used to disrupt their ability to divide, but the effect is slow.
  • Prevention includes proper hygiene and avoidance of aerosols and contaminated fomites.

Bacillus

  • Rod-shaped, facultative anaerobes (can be aerobic or anaerobic).
  • Occur singly, in pairs, or chains; form endospores.
  • Some pathogenic strains produce anthrax toxins (Bacillus anthracis).
  • Humans can contract Bacillus endospores from infected animals via inhalation, breaks in the skin, or ingestion.
Bacillus anthracis
  • The only Bacillus species that causes anthrax.
  • Three types of anthrax:
    • Gastrointestinal anthrax: Rare.
    • Cutaneous anthrax: Produces an ulcer called an eschar (black scar).
      • Fatal in 20% of untreated patients.
    • Inhalation anthrax: Rare but extremely dangerous with a high mortality rate (80-100%).
Diagnosis, Treatment and Prevention
  • Diagnosis: Look for large, non-motile, gram-positive bacilli in lung or skin samples using a biopsy.
  • Treatment: Most antimicrobials are effective (e.g., amoxicillin, ampicillin, penicillin).
    • Due to the gram positive cell wall.
  • Control the disease in animals:
    • Slaughter and incinerate infected animals.
  • Prevention: Effective vaccine available that requires multiple doses and boosters.
    • Typically given to people who work in conditions with potential exposure, military personnel, and during outbreaks.

Streptococcus

  • Includes Streptococcus pyogenes, a causative agent of strep throat.
Streptococcus pyogenes
  • Possesses structural components to evade phagocytosis.
    • M protein destabilizes complement proteins.
    • Hyaluronic acid (HA) in the capsule, which helps hide the bacteria from the white blood cells because the body recognizes it as self.
  • Possesses enzymes:
    • Streptokinases break down blood clots, facilitating the spread of infection.
    • Deoxyribonucleases break down DNA of lysed white blood cells, reducing pus firmness.
    • C5a peptidase breaks down complement protein C5a, compromising the inflammatory response.
    • Hyaluronidase breaks down hyaluronic acid, facilitating the spread of streptococcus through tissues.
  • Possesses pyrogenic toxins:
    • Stimulate fever, rash, and shock.
  • Possesses streptolysins:
    • Lyse red blood cells, causing tissue death due to lack of oxygen and nutrients.
Epidemiology
  • Typically infects the pharynx or the skin.
  • Often causes diseases when normal microbiota are depleted.
  • Spreads via respiratory droplets.
Group A Streptococcal Diseases
  • Pharyngitis (strep throat): Inflammation of the pharynx.
    • Characterized by white pustules.
  • Scarlet fever: Occurs following streptococcal pharyngitis infections.
    • Characterized by a chest rash that spreads across the body.
  • Necrotizing fasciitis: Tissue death facilitated by factors like C5a peptidase, hyaluronidase, and streptolysins.
    • Requires amputation.
  • Pyoderma: Pus-producing lesions are found on exposed skin.
  • Erysipelas: Infection and inflammation of lymph nodes surrounding a streptococcal infection.