Gram Positive Bacilli: Spore-Forming (Nash)

GRAM POSITIVE DON'T HAVE ENDOTOXINS!!

Learning Objectives

  • Understand the classification of Gram-positive bacilli, specifically focusing on the genera Bacillus and Clostridium.

  • Recognize the characteristics that define Gram-positive bacilli, including their unique structural features and spore formation.

  • "bacillus" that is NOT CAPITALIZED means "rod-shaped"

  • "Bacillus" capitalized and in italics is a GENUS of gram positive rods

  • Gram-positive bacilli are rod-shaped bacteria that can be classified into two primary genera: Bacillus and Clostridium.

  • Characterized by a thick peptidoglycan layer which contributes to their Gram-positive nature.

  • Notable for spore formation, making them resilient in various environments.

  • There is only one lipid bilayer (one cell membrane) in Gram positive bacteria

Bacillus Genus

  • Aerobe (needs oxygen) to facultative anaerobes (grow both in the presence and absence of oxygen)

  • Worldwide soil saprophytes (bacteria and fungi, that break down dead organic matter in the soil).

  • Bacillus anthracis

  • Causative agent of anthrax.

  • Notable for its role as a biological warfare agent; spores can be transmitted through inhalation (woolsorters' disease), exemplified by the 2001 incident.

  • Can also lead to cutaneous anthrax (95%) when in contact with infected animal hides.

  • Produces deadly exotoxins that can lead to severe symptoms like fever and colitis.

  • Treatment includes antibiotics like ciprofloxacin and doxycycline but must be administered quickly.

  • Polyglutamyl (amino acid) capsule that survives phagocytosis

  • Exotoxins -factor A- lethal factor or edema factor (cyclic AMP, adenylate cyclase) and protective antigen factor B

  • Bacillus cereus

  • Produces enterotoxins (type of exotoxin that specifically affect the intestines) that causes food poisoning, often linked to improperly stored rice (fried rice), particularly pasta.

  • Produces two types of toxins:

  • heat-stable (from rice) causing vomiting (1-6 hours)

  1. Aureus has heat stable toxin as well

  • heat-labile (from meats and vegetables) causing diarrhea (cAMP toxin like E. coli).

  • Easy to remember due to its association with cereal.

  • Motile

  • Not encapsulated

Clostridium Genus (Clostridia)

  • Gram positive spore forming rod

  • Notable for being anaerobic spore-forming bacilli found predominantly in soil.

  • They cannot grow well if there is oxygen involved. They ferment into organic acids.

  • They make all kinds of digestive enzymes.

  • 2 make neurotoxins, 2 make cytotoxins (cyto = cell)

  • Ubiquitious saprophytes or normal flora

  • Produce a foul odor (butyric fermentation)

  • Clostridium tetani

  • Motile

  • Lockjaw: comes from masseter muscle clamping the jaw shut

  • Terminal spores (squash racket)

  • Causes tetany (uncontrollable contraction  of muscle)

  • Classic mode of entry is via a rusty nail

  • Tissue around puncture gets anaerobic due to the other bacteria eating the oxygen.

  • It can grow in an umbilical cord stump in a baby

  • Produces a single exotoxin:

  • Causes tetanus, often contracted through rusty nails.

  • Tetanus spore germinates in anaerobic wounds, producing a potent neurotoxin that leads to muscle spasms and rigidity.

  • Tetanus pts: have Rictus ("smile" like the Joker)

  • Prevention through vaccination (tetanus toxoid vaccines--DPT), with boosters (Td booster, tetanus toxoid) needed every ten years.

  • Treatment:

  • We can block the toxin with antibodies.

  • "Toxoid" is a chemically modified toxin that doesn't kill you. It releases IgG (it stays after a couple years).

  • Clostridium botulinum

  • Oval subterminal spores

  • Motile

  • Food borne intoxication

  • Neurotoxin -- Most LETHAL known!!

  • The spore is heat resistant

  • Produces 1 or more of the zinc protease botulinum toxin, which leads to flaccid paralysis with diplopia (double vision), dysarthria and dysphonia (slurred abnormally pitched speech) often from foodborne sources due to improper canning practices.

  • Toxin

  • The botulinum toxin is an "AB" toxin

  • The botulinum toxin also makes a "shield" protein that prevents the toxin from being digested.

  • The botulinum toxin is a protease, cleaves SNARE, but it BLOCKS Acetylcholine release. Acetylcholine is an excitatory neurotransmitter.

  • The toxin BLOCKS excitement, so the person gets flaccid paralysis

  • Type C1 and D botulinum exotoxin are encoded by bacteriophage.

  • Type A is the most potent

  • Type A, B, E, F are chromosomal and block acetylcholine release

  • Highly lethal with a very low lethal dose (LD50-lethal dose for 50% of the people who take it).

  • Serious risks associated with infant botulism as spores can colonize a baby’s immature gut.

  • Ways to get it

  • Spore gets into food and germinates (home canning)

  • Baby EATS spores (like in honey) and they colonize the GI tract, and make toxin

 

  • Clostridium perfringens

  • Large rectangular spores

  • Non-motile

  • Gram positive spores that live in the soil

  • Known for causing gas gangrene, particularly in traumatic situations.

  • It makes ALL kinds of awful lytic enzymes, exotoxins

  • Alpha toxin is a lecithinase, breaks membranes. Lecithin is part of the lipid bilayers in cell membranes meaning C. perfringens is a cytotoxin.

  • GAS GANGRENE:

  • Treatment: DEBRIDE (cut off) tissue, Hyperbaric oxygen, Antibiotics (penicillin)

  • Produces gas in tissue, evident through crepitus (crackling of the skin, like bubble wrap when you press it), and requires urgent surgical intervention.

  • FOOD Poisoning: Can also cause food poisoning, especially in settings like picnics where food is left out too long.

  • The person would get water diarrhea

  • Clostridium perfringens makes an entertoxin (exotoxin) in food

  • Treatment: Combo of penicillin and clindamycin

  • Clostridium difficile (now called Clostridioides difficile)

  • Large oval subterminal spores

  • Toxin A (enterotoxin = exotoxin): Brings a lot of neutrophils; very inflammatory.

  • Toxin B (Cytopathic agent): causes actin to break down in the cytoskeleton and kills cells. From there, you get a pseudomembrane (fibrin, cells, bacteria).

  • Treatment includes oral vancomycin (works on gram positive cell walls), metronidazole (works on any anaerobes), and fecal microbiota transplants for restoring healthy gut flora.

 

  • Pseudomembranous entercolitis or anitbiotic associated colitis as a consequence of elimination of normal intestinal flora

  • Abdominal pain with a watery diarrhea and leukocytosis

  • Patients secrete large numbers of spores in feces

  • Grows in people's colons:

  • Spores get into colon and germinate

  • Doesn't thrive in normal gut flora or microbiome, but if someone has had clindamycin (BOARD Q!!) or ampicillin and has wiped out the flora, C. diff would prosper and ovegrow

  • Major concern in hospitals, leading to antibiotic-associated colitis.

  • Thrives when normal gut microbiota are disrupted; produces two toxins that inflame the colon and kill cells.

Treatment Considerations

  • Antibiotics: Penicillin and other appropriate antibiotics are essential for treating many gram-positive infections.

  • Importance of rapid treatment; both Bacillus anthracis and Clostridium infections can escalate quickly.

  • Emphasis on effective management of infections through understanding the biochemistry and environmental factors contributing to pathogenicity.

  1. What is MRSA?

    • MRSA stands for Methicillin-Resistant Staphylococcus Aureus, a type of staph bacteria that is resistant to many antibiotics, making it difficult to treat. It can cause a variety of infections, ranging from skin infections to more serious infections like pneumonia or bloodstream infections.

  2. What is the grouping system for beta Strep called? What are common groups?

    • The grouping system for beta Streptococcus is called the Lancefield classification. Common groups include Group A (Streptococcus pyogenes) and Group B (Streptococcus agalactiae).

  3. What are virulence mechanisms for Pneumococcus?

    • Pneumococcus, or Streptococcus pneumoniae, has several virulence mechanisms, including a polysaccharide capsule that inhibits phagocytosis, the production of pneumolysin (a cytotoxin that can damage host cells), and the ability to produce enzymes that break down host tissues.

  4. What other coccus looks similar but is harder to treat?

    • Coagulase-negative Staphylococcus, such as Staphylococcus epidermidis, resembles Staphylococcus aureus but is generally harder to treat due to its adherence to medical devices and its ability to form biofilms.

  5. What other questions occur to me?

    • Questions may include:

      • How does antibiotic resistance develop in these bacteria?

      • What are effective prevention strategies for MRSA and Pneumococcal infections?

      • What role do vaccinations play in controlling infections caused by these organisms?