Antimicrobial Agents and Microbial Virulence Factors

Posted on Aug 23, 2024 in Biology

Chapter 9: Sanitization and Disinfection

Disinfection in Public Places

Action of Antimicrobial Agents:

  1. Alteration of cell wall or cytoplasmic membrane
  2. Interference with protein and nucleic acid structures

Effectiveness of Antimicrobial Agents:

  • High-Level: Kill all pathogens (besides prions)
  • Intermediate-Level: Kill fungal spores, protozoan cysts, viruses, and pathogenic bacteria.
  • Low-Level: Kill vegetative bacteria, fungi, protozoa, and some viruses.

Antimicrobial Agents: Heat, dry heat, refrigeration and freezing, lyophilization, filtration, osmotic pressure, radiation, and chemical.

Pasteurization:

  1. 30 min @ 63°C
  2. Flash: 15 sec @ 72°C
  3. Ultra High-Temp: 1 sec @ 134°C

Dry Heat:

  • Flame (1500°C)
  • Ovens (160-176°C)

Chemical Methods

Target cell walls, cytoplasmic membranes, proteins, and DNA. Most effective against enveloped viruses and vegetative cells of bacteria, fungi, and protozoa.

Phenols: Intermediate to low-level disinfectant. They affect the 3D structures of proteins and plasma membranes.

Aldehydes: Used to embalm and disinfect rooms. Cross-linked with amino, hydroxyl, sulfhydryl, and carboxyl groups of molecules. Denatures proteins, inactivates nucleic acids.

Alcohol: Intermediate-level disinfection, evaporates rapidly.

Halogens: Intermediate-level antimicrobial chemicals. Damage enzymes via oxidation: e.g., bleach, iodine.

Oxidizing Agents: Peroxides, ozone, and peracetic acid kill by oxidation of microbial enzymes. (High-level disinfectant and agent)

Surfactants: Soaps and detergents. Detergents are positively charged organic surfactants (low-level).

Heavy Metals: Ions alter the 3D shape of proteins, inhibiting or eliminating their functions. (Low-level) Thimerosal used to preserve vaccines.

Gaseous Agents: Ethyl oxide, propyl oxide – closed chambers, denature proteins and DNA by cross-linking functional groups. Used in hospitals and dental offices.

Antimicrobial Drugs

Antibiotics, semi-synthetic and synthetic chemicals. Mostly for the treatment of disease, some for food preservation.

Factors Affecting Antimicrobial Methods:

  1. Nature of the site to be treated
  2. Degree of susceptibility of microbes involved
  3. Environmental conditions

Methods of Evaluating Disinfectants and Antiseptics: Use-dilution test, disk diffusion method, and in-use test.

Efficacy:

  • (MIC) Minimum Inhibitory Concentration = Minimum concentration to stop growth.
  • (MBC) Minimum Bactericidal Concentration = Minimum concentration to kill everything – plate the clear MIC tubes to see which killed.

Mechanisms of Resistance

  • Produce enzymes that destroy or deactivate the drug
  • Slow or prevent entrance of the drug
  • Alter the target of the drug
  • Alter the metabolic pathway or bypass it
  • Pump out the drug

Multiple Resistance & Cross Resistance: Resistant to drugs with the same structure. Multiple resistance is common when R-plasmids are exchanged.

Chapter 10: Antibiotics and Antimicrobial Agents

Penicillin

In 1928, Fleming noticed penicillin. In 1940, Howard Florey and Ernest Chain discovered its healing properties in humans (perfected the purification). Albert Alexander was treated.

Gerhard Domagk: Sulfonamide effects on folic acid synthesis. Tested on his child.

Inhibition of Cell Wall Synthesis

Vancomycin and Cycloserine: Affect alanine-alanine bridges between NAMs.

Bacitracin: Blocks secretion of NAG and NAM from the cytoplasm.

Isoniazid: Disrupts arabinogalactan-mycolic acid in mycobacterial species, used for long-term treatment.

Inhibition of Protein Synthesis: Translation

Streptomycin and Gentamycin: Alter 30S subunits.

Aminoglycosides: Change 3D shape.

Tetracycline: Blocks tRNA docking site.

Chloramphenicol: Blocks enzymatic activity of the ribosome.

Erythromycin: Binds to 50S and prevents movement. mRNA cannot move through the ribosome properly.

Disruption of Cytoplasmic Membranes

Amphotericin B (Polyene): Attaches to ergosterol found in fungal membranes. Bacteria lack sterols and are not susceptible, but it is toxic to humans. Cholesterol is similar to ergosterol.

Polymyxin: Disrupts cytoplasmic membranes of Gram-negative bacteria, toxic to humans.

Pyrazinamide: Disrupts transport across the plasma membrane in Mycobacterium tuberculosis.

Inhibition of Metabolic Pathways

Heavy Metals: Paralyze, inactivate enzymes.

Metabolic Antagonists: Sulfonamides (Prontosil), para-aminobenzoic acid analog. PABA → folic acid.

Inhibition of Nucleic Acid Synthesis

  1. Bind to DNA – affect replication and transcription, Actinomycin.
  2. Block DNA replication – nucleotide analogs.
  3. Inhibit RNA polymerase – affects mRNA transcription and synthesis – affects both types of cells: viruses, cancer, research.

Antiviral Agents

Amantadine, Rimantadine: Neutralize the acidity of phagolysosomes and prevent viral uncoating. Attachment to the cell is blocked (analogs), peptides/sugars.

Ideal Agents

Readily available, inexpensive, chemically stable, easily administered, non-toxic or allergenic, selectively toxic against a wide range of pathogens.

Evaluation of Antimicrobial Agents

Spectrum of action, efficacy – dosage required to be effective, route of administration, safety, and side effects.

Efficacy Measured By: Diffusion susceptibility test, minimum inhibitory concentration test, and E-test.

Chapter 14: Virulence Factors of Pathogens

Virulence Factors

  • Adhesion
  • Extracellular enzymes
  • Toxins
  • Anti-phagocytic factors

Adhesion

The host’s ability to change or block the glycoprotein can prevent infection. The inability to attach to attachment proteins or adhesion renders the microorganism avirulent.

Extracellular Enzymes

Enzymes secreted by the pathogen, dissolve structural chemicals in the body, help pathogens maintain infection, invade further, and avoid body defenses.

Toxins

Chemicals produced by pathogens: harm tissue or trigger host responses that cause damage. Two types: exotoxins and endotoxins.

Anti-phagocytic Factors

  1. Bacterial Capsule: Often composed of chemicals found in the body and not recognized as foreign. Can be slippery, difficult for phagocytes to engulf.
  2. Anti-phagocytic Chemicals: Prevent fusion of lysosomes and phagocytic vesicles or destroy phagocytic white blood cells – leukocides.