Pathogenic Microorganisms 222 PHARM

Pathogenic Microorganisms 222 PHARM

• Course covers pathogenic microorganisms.
• The presentation details bacterial structures and functions.

Bacterial Structures and Function

• Objectives include microscopic bacterial structure details, distinguishing Gram-positive and Gram-negative cell walls, describing bacterial movement, and spore formation.

Bacterial Structure

• Bacteria consist of both essential and additional structures.

• Essential: cell wall, cell membrane, cytoplasm, ribosomes, and nuclear material.

• Additional (non-essential): capsule, slime layer, flagella, pili, fimbriae, inclusions, spores, and plasmids.

• A diagram shows Gram-positive and Gram-negative structures.

• Gram-positive: thicker peptidoglycan layer and teichoic acids; no outer membrane.

• Gram-negative: thinner peptidoglycan layer, outer membrane, and lipopolysaccharides (LPS); periplasmic space between layers.

Structure of Eubacteria

• External structures (extracytoplasmic): glycocalyx, flagella, pili, and fimbriae.
• Cell envelope: outer membrane, cell wall, and cell membrane.
• Internal structures (intracytoplasmic): cytoplasm, ribosomes, nuclear material, inclusions, spores, and plasmids.

Cell Wall Structures

• Key components: outer membrane, peptidoglycan, teichoic acids, and periplasm.
• Cytoplasmic membrane (CM) is also included.
• Gram positive and Gram negative cell wall composition differ significantly.

Cell Wall (CW)

• The CW is the outermost component of bacteria, external to the cytoplasmic membrane.
• Highly rigid and plays a role in shaping the cell.
• Thickness and composition vary based on bacterial type.
• Two major types: Gram-positive and Gram-negative.
  • Diagram illustrating gram positive and gram negative
    • Gram-positive has a thick layer; Gram-negative a thin layer.
    • LPS and porins, components of gram negative, not present in gram positive cell walls.

Gram Positive and Gram Negative Cell Wall

• Summarized comparison of Gram-positive and Gram-negative cell walls.
  • Presence/absence of outer membrane, peptidoglycan thickness, presence of teichoic acids.
  • The table shows variations in thickness (Gram+ vs. Gram-), layers, and other component presences in the walls.

Outer Membrane (OM)

• Present only in Gram-negative bacteria, outside peptidoglycan layer.
• Asymmetric lipid bilayer: composed of LPS, porins, phospholipids, and lipoproteins.

Lipopolysaccharides (LPS)

• Hydrophilic, extends into cell exterior, and highly variable between species.
  • A specific type of immunogenic O-antigen found on E. coli (O157:H7).
• Includes an O-antigen, core oligosaccharide, and lipid A.
• Lipid A is hydrophobic endotoxin/pyrogen.

Porins Proteins

• Membrane proteins forming channels, found in both halves of the OM.
• Responsible for transporting hydrophilic molecules.
• Loss of porins can lead to antibiotic resistance.
  • Other associated proteins, like OmpA, serve as receptors and stabilizers

Lipoteichoic Acids

• Play a role in stabilizing OM structure, covalently bonded to peptidoglycan, and anchoring inner membrane leaflet.

Phospholipids

• OM inner leaflet resembles the cytoplasmic membrane (CM); outer leaflet contains LPS.

Functions of OM

• Conferring negative charge to cells
• Maintaining bacterial structure
• Providing protection against adverse conditions
• Acting as channels through OmpC and OmpF
• Binding receptors for some viruses and aiding mating conjugation
• Initiating innate immune responses.

Peptidoglycan (PDG)

• Found in all eubacteria, surrounding the cytoplasmic membrane (CM).
• Highly rigid structure that prevents osmotic lysis.
• Maintains cell shape, permeable to ions, amino acids, and sugars.
• Composed of repeating disaccharide units (NAG and NAM) linked by short peptides.
• Cross-linking of peptide chains occurs between different layers via 3rd amino acid.
  • Specific peptides link specific organisms.
• Cross-linking is essential for rigidity.

Teichoic Acids (TA)

• Found only in Gram-positive bacteria, contributing to 50% of the cell wall weight.
• Cell surface anionic glycopolymers.
• Responsible for negative charge.
• Highly immunogenic.
• Mediate adherence to mucosal cells.
  • WTA and LTA are two key types.
  • Two-part structure (disaccharide unit) made of N-acetylmannosamine and NAG-1-phosphate.

Types of Teichoic Acids

• WTA (Wall Teichoic Acid): main chain of glycerol or ribitol linked by phosphodiester bond.
• LTA (Lipoteichoic Acid): linked to cytoplasmic membrane with glycolipid anchor.
  • Cell shape determination and regulation, along with pathogenesis and antibiotic resistance are all contributed to by these two types.

Atypical Cell Walls

• Acid-fast bacteria (e.g., Mycobacterium): have a high lipid content (up to 60%) with mycolic acids in their cell walls.
  • Mycolic acids are long-chain fatty acids covalently bound to peptidoglycan.
    • Additional components, such as mannan caps, lipoproteins, and other proteins create a thick waxy layer for protection.

Wall-less (Cell Walls Deficient) Bacteria

• Mycoplasmas, Archaea, and L-forms lack cell walls.
  • Mycoplasmas have sterols in their plasma membrane.
  • Archaea have pseudomurein walls (different structure than peptidoglycan).
  • L-forms lose cell walls under certain conditions and can reacquire them.

L-Forms

• Defective cell wall bacteria.
  • Induced artificially via lysozyme digestion, penicillin treatment, or hypertonic solutions.
  • Two types: protoplasts (wall-less Gram-positive) and spheroplasts (wall-less Gram-negative).
    • Protoplasts and spheroplasts are remarkably stable, able to divide normally, and have great plasticity and resilience to survive and restore cell walls in different conditions.

Periplasmic Space (periplasm)

• In Gram-negative bacteria, space between the outer and cytoplasmic membranes.
• Contains enzymes and gel-like solution of proteins.
  • Includes biosynthetic enzymes, binding proteins for transporting molecules, and enzymes degrading antibiotics.

Plasma Membrane

• Encloses the cytoplasm, selectively permeable, and less rigid than eukaryotic cell membranes. - Mostly composed of phospholipids. - Proteins embedded in the phospholipid bilayer regulate transport, metabolism, and other functions.
  • No sterols in most bacterial PMs with exception of mycoplasma.
• Proteins and phospholipids are present in a 3:1 ratio in the membrane.

Mesosomes

• Invaginations of the cytoplasmic membrane, crucial for cell wall formation during cell division.
  • Involved in oxidative phosphorylation.

Functions of Plasma Membrane

• Selective permeability: semipermeable nature of the membrane allows controlled passage of molecules. - Contains carrier proteins that aid in transport activities.
• Regulation of cell division: crucial for proper bacterial multiplication.
  • Excretion of proteins like IgA protease is vital for bacterial virulence and immune evasion.
    • Contains enzymes for ATP production and oxidative phosphorylation processes.
  • Damage to plasma membrane by antibiotics and other factors can lead to cell leakage.

Transport Across the Cell Membrane

• Key rule is movement from high to low concentration.
• Diffusion describes the spontaneous process.
• Passive transport/facilitated diffusion are crucial transport mechanisms depending if energy is required. Transport via carrier proteins and channels are also prominent means of transport.

Types of Transport

• Based on energy use: passive (no energy) vs active (energy required). - Various mechanisms including uniporters, symporters, and antiporters for directed transport.

Antibiotics Action on Cell Membrane

• Polymyxins act by electrostatic interaction with negatively charged lipids in the OM.
  • Can destabilize the membrane, increase permeability, causing leakage, and cell death.
  • Inhibition of type II NADH oxidoreductase is another mechanism.
    • Primarily acts on Gram-negative bacteria but has varying effects on other bacterial cell types.