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Microbial Metabolism, Growth, Control, and Antimicrobial Drugs – Study Guide

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Microbial Metabolism

Catabolism vs. Anabolism

Microbial metabolism encompasses all chemical reactions that occur within a microbe. These reactions are divided into two main categories:

  • Catabolism: The breakdown of complex molecules into simpler ones, releasing energy. Example: Glycolysis.

  • Anabolism: The synthesis of complex molecules from simpler ones, requiring energy input. Example: Protein synthesis.

Types of Microbial Nutritional Patterns

  • Chemoheterotroph: Organisms that obtain energy and carbon from organic compounds. Most bacteria, fungi, and animals are chemoheterotrophs.

  • Chemoautotroph: Organisms that obtain energy from inorganic compounds and carbon from CO2. Example: Nitrifying bacteria.

  • Photoheterotroph: Organisms that use light for energy but require organic compounds as a carbon source. Example: Some purple non-sulfur bacteria.

  • Photoautotroph: Organisms that use light for energy and CO2 as a carbon source. Example: Cyanobacteria, plants.

Enzymes: Properties and Regulation

  • Structure: Enzymes are biological catalysts, usually proteins, with an active site where substrates bind.

  • Factors Influencing Enzyme Activity:

    • Temperature

    • pH

    • Substrate concentration

    • Presence of inhibitors

  • Function: Enzymes lower the activation energy of reactions, increasing reaction rates.

  • Types of Enzymatic Inhibition:

    • Competitive inhibition: Inhibitor binds to the active site, blocking substrate.

    • Noncompetitive inhibition: Inhibitor binds to an allosteric site, changing enzyme shape.

Cellular Respiration vs. Fermentation

  • Cellular Respiration: Involves glycolysis, Krebs cycle, and electron transport chain. Final electron acceptor is usually oxygen (aerobic) or another inorganic molecule (anaerobic).

  • Fermentation: Involves glycolysis followed by conversion of pyruvate to various end products. Final electron acceptor is an organic molecule. Less ATP produced than respiration.

Oxidase Test

  • Detects the presence of cytochrome c oxidase enzyme in bacteria.

  • Used to differentiate between bacterial species, especially Gram-negative rods.

Lipid and Protein Catabolism

  • Lipid Catabolism: Lipases break down lipids into fatty acids and glycerol. Fatty acids enter β-oxidation to generate acetyl-CoA for the Krebs cycle.

  • Protein Catabolism: Proteases break down proteins into amino acids, which are deaminated and enter central metabolic pathways.

Importance of Microbial Metabolism

  • Understanding metabolism helps in identifying microbes, developing antibiotics, and controlling microbial growth.

  • Metabolic pathways are targets for antimicrobial drugs.

Microbial Growth

Growth Curve Phases

Bacterial growth in a closed system follows a predictable pattern:

  • Lag Phase: Cells adapt to environment; no increase in number.

  • Log (Exponential) Phase: Rapid cell division; cells are most susceptible to antibiotics.

  • Stationary Phase: Nutrient depletion and waste accumulation slow growth; cell death equals cell division.

  • Death Phase: Cells die at an exponential rate.

Clinical Importance: The log phase is critical for antibiotic effectiveness; stationary phase cells may be more resistant to treatment.

Oxygen Requirements for Growth

  • Obligate Aerobes: Require oxygen; use aerobic respiration.

  • Facultative Anaerobes: Grow with or without oxygen; use aerobic respiration, anaerobic respiration, or fermentation.

  • Obligate Anaerobes: Cannot tolerate oxygen; use anaerobic respiration or fermentation.

  • Aerotolerant Anaerobes: Do not use oxygen but tolerate its presence; use fermentation.

  • Microaerophiles: Require low levels of oxygen.

Protective Enzymes:

  • Superoxide Dismutase (SOD): Converts superoxide radicals to hydrogen peroxide.

  • Catalase: Converts hydrogen peroxide to water and oxygen.

  • Obligate aerobes and facultative anaerobes possess both enzymes; obligate anaerobes lack them.

Temperature Requirements

  • Psychrophiles: Grow at 0–15°C.

  • Mesophiles: Grow at 20–45°C (most human pathogens).

  • Thermophiles: Grow at 55–80°C.

  • Hyperthermophiles: Grow above 80°C.

pH Requirements

  • Acidophiles: Grow best at pH < 5.5.

  • Neutrophiles: Grow best at pH 5.5–8.0.

  • Alkaliphiles: Grow best at pH > 8.0.

Halophiles and Osmosis

  • Obligate Halophiles: Require high salt concentrations for growth.

  • Facultative Halophiles: Can tolerate high salt but do not require it.

  • Halophilism relates to osmosis, as high salt environments draw water out of cells, requiring adaptations to prevent dehydration.

Control of Microbial Growth

Terminology

  • Sterilization: Destruction of all microbial life, including spores.

  • Disinfection: Destruction of vegetative pathogens on inanimate objects.

  • Antisepsis: Destruction of pathogens on living tissue.

  • Sanitization: Lowering microbial counts to safe public health levels.

-Cidal vs. -Static Treatments

  • -Cidal: Treatments that kill microbes (e.g., bactericidal).

  • -Static: Treatments that inhibit microbial growth (e.g., bacteriostatic).

Physical Control Methods (Examples)

  • Heat: Moist heat (autoclaving, boiling) and dry heat (oven) denature proteins.

  • Filtration: Removes microbes from liquids or air using physical barriers.

Chemical Control Methods (Examples)

  • Alcohols: Denature proteins and disrupt membranes (e.g., ethanol, isopropanol).

  • Halogens: Oxidize cellular components (e.g., chlorine, iodine).

Antimicrobial Drugs

Bacteriostatic vs. Bactericidal

  • Bacteriostatic: Inhibit bacterial growth without killing (e.g., tetracycline).

  • Bactericidal: Kill bacteria directly (e.g., penicillin).

Broad-Spectrum vs. Narrow-Spectrum Drugs

  • Broad-Spectrum: Effective against a wide range of microbes (e.g., tetracycline).

  • Narrow-Spectrum: Effective against specific groups (e.g., penicillin G for Gram-positive bacteria).

Superinfections

  • Occur when normal microbiota are destroyed by antibiotics, allowing opportunistic pathogens to proliferate (e.g., Clostridioides difficile infection after broad-spectrum antibiotic use).

Dosage and Route of Administration

  • Proper dosage ensures drug effectiveness and minimizes resistance.

  • Route (oral, intravenous, topical) affects drug absorption and distribution.

Drug Interactions

  • Positive Interactions (Synergism): Combined drugs have enhanced effect (e.g., trimethoprim and sulfamethoxazole).

  • Negative Interactions (Antagonism): One drug reduces the effect of another.

Mechanisms of Action of Antibacterial Drugs

  • Inhibition of Cell Wall Biosynthesis: e.g., β-lactams (penicillins, cephalosporins).

  • Inhibition of Protein Synthesis: e.g., tetracyclines, macrolides.

  • Disruption of Membrane Function: e.g., polymyxins.

  • Inhibition of Nucleic Acid Synthesis: e.g., quinolones, rifamycins.

  • Inhibition of Metabolic Pathways: e.g., sulfonamides (folic acid synthesis inhibitors).

Modes of Action: Antifungal, Antiprotozoan, Antihelminthic, and Antiviral Drugs

  • Antifungal: Target ergosterol in fungal membranes (e.g., amphotericin B).

  • Antiprotozoan: Inhibit nucleic acid or protein synthesis (e.g., metronidazole).

  • Antihelminthic: Disrupt helminth metabolism or neuromuscular function (e.g., mebendazole).

  • Antiviral: Inhibit viral entry, replication, or release (e.g., acyclovir, oseltamivir).

Development and Acquisition of Drug Resistance

  • Microbes can acquire resistance through genetic changes:

    • Transformation: Uptake of free DNA from the environment.

    • Transduction: Transfer of DNA by bacteriophages.

    • Conjugation: Transfer of plasmids via direct cell-to-cell contact.

Mechanisms of Antimicrobial Drug Resistance

  • Enzymatic destruction or inactivation of the drug (e.g., β-lactamases).

  • Alteration of drug target sites.

  • Decreased permeability or increased efflux of the drug.

  • Bypass of metabolic pathways inhibited by the drug.

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