BIOL 265-61 Exam 3 Preparation

CH20 and CH8: Parts 1-4.

Antibiosis

Inhibition of one microorganism by another.

Antibiotics

Substances produced by microorganisms that inhibit bacteria in small amounts.

Antimicrobial Drugs

A broader term that includes naturally produced antibiotics and synthetic drugs.

Sulfa Drugs (Sulfonamides)

Synthetic antimicrobial drugs that inhibit bacterial folic acid synthesis.

Ex. Prontosil Red (1932) found to control Streptococcal infections in mice.

Streptomyces

Filamentous soil bacteria that produce more than half of useful antibiotics.

Antibiotic Resistance

Occurs when bacteria become less susceptible to drugs that

previously controlled them.

Selective Toxicity

A drug harms the pathogen while causing minimal damage to the human host.

Differences between bacterial cells (prokaryotes) and human cells (eukaryotes):

• Cell Wall

• Ribosomes

• Metabolism

Antifungal, antiprotozoal, and antihelminthic drugs are more difficult to develop because:

They are also eukaryotes and resemble human cells.

Antiviral drugs are also difficult to develop because:

Viruses reproduce inside host cells and use their cellular machinery to produce more viruses.

Narrow-spectrum Antibiotic

Acts against a limited group of microorganisms.

Ex., Penicillin G primarily affects Gram-positive bacteria.

Broad-spectrum Antibiotic

Acts against a wide range of bacteria, including many Gram-positive and Gram-negative species.

Ex., broad-spectrum antibacterial drugs.

Porins

Water-filled channels in the outer membrane, containing lipopolysaccharide (LPS).

Superinfection

Overgrowth of an unaffected microorganism or persistence of an infection due to antibiotic resistance.

Bactericidal

Kill microorganisms directly.

Bacteriostatic

Stop or inhibit microbial growth. The host's immune system (phagocytosis, antibody production) usually eliminates the microorganisms.

Inhibition of Cell Wall Synthesis:

• Prevents proper formation of peptidoglycan.

• Weakens the cell wall, causing lysis.

• Primarily affects actively growing bacteria.

• Human cells lack peptidoglycan walls, providing selective toxicity.

Ex. Penicillin.

Inhibition of Protein Synthesis:

• Bacterial ribosomes are 70s.

• Eukaryotic cytoplasmic ribosomes are 80s.

• These differences allow selective toxicity.

• Some antibiotics can also affect the host’s mitochondria, which contain bacterial-like ribosomes.

Ex. Chloramphenicol, erythromycin, streptomycin, and tetracyclines.

Injury to Plasma Membrane:

Some polypeptide antibiotics disrupt membrane permeability of Gram (-) bacteria, causing essential metabolites and ions to leak out.

Antifungal Drugs

Bind to sterols in fungal membranes, disrupting membrane function.

Lonophores

Allow uncontrolled movement of cations across membranes.

Inhibition of Essential Metabolite Synthesis: Antimetabolites

Resemble normal enzyme substrates and competitively inhibit metabolic reactions.

Mechanism of action: A competitive inhibitor.

Resembles para-aminobenzoic acid (PABA) (bacteria use it to synthesize folic acid), limiting growth.

Humans obtain folate from ____________.

Diet

Sulfonamides and Trimethoprim (SMZ-TMP)

• Blocks two successive steps in bacterial folate metabolism.

• Used for selected UTI’s and other susceptible bacterial infections.

Silver Sulfadiazine: Used in burn patients to help prevent or treat infections.

Ergosterol

A major sterol in fungal cell membranes; human cell membranes primarily contain cholesterol.

Penicillins

1. Natural Penicillins: produced naturally by Penicillium molds.

2. Semisynthetic Penicillins: produced to improve resistance to β-lactamases or broaden the spectrum.

B-lactam Antibiotic Family

They kill bacteria by binding to penicillin-binding proteins (PBPs) (transpeptidases), which stops the bacteria from building their cell walls and causes them to rupture.

Defined by a core beta-lactam ring in their chemical structure.

β-glucan

An important component of fungal cell walls that is absent from human cells.

High-yield Distinction

Polyenes bind to ergosterol; azoles and allylamines inhibit its synthesis; echinocandins inhibit fungal cell wall synthesis.

Penicillins + Beta-lactamase Inhibitors

Clavulanic acid inhibits certain beta-lactamases and protects the partner penicillin.

Amoxicillin + Clavulanic Acid (Augmentin).

Penicillinase-resistant Penicillins

Beta-lactamases break the beta-lactam ring and inactivate susceptible antibiotics.

Methicillin and oxacillin. Not good against MRSA.

Antiviral Drugs: Acyclovir

Herpesvirus DNA replication.

Antiviral Drugs: Remdesivir

Viral RNA polymerase.

Antiviral Drugs: Oseltamivir

Influenza neuraminidase.

Antiviral Drugs: Nirmatrelvir

SARS-CoV-2 protease.

MRSA (Methicillin-resistant Staphylococcus aureus)

Gram-positive bacterium. Vancomycin specifically targets and kills Gram-positive bacteria.

Metronidazole

Protozoa and anaerobic bacteria.

Praziquantel

Tapeworms and flukes.

Albendazole

Helminth microtubules

Ivermectin

Paralysis of susceptible parasites.

Isoniazid (INH)

Inhibits mycolic acid synthesis. Important TUBERCULOSIS DRUG.

Note: Tuberculosis is treated with multiple drugs to reduce the development of resistance. An example of one that would be combined with others is Ethambutol.

Aminoglycosides

30S; mRNA misreading.

Tetracyclines

30S; block tRNA attachment.

Glycylcyclines

30S; block protein synthesis and resist certain efflux mechanisms.

Pleuromutilins

Ribosome; interfere with protein synthesis.

Antimicrobial susceptibility testing helps determine _____________________________________________________.

Which drug is most likely to inhibit or kill a specific pathogen.

MIC (Minimum Inhibitory Concentration)

The lowest concentration of an antimicrobial drug that prevents visible microbial growth under defined test conditions.

MBC (Minimum Bactericidal Concentration)

The lowest concentration of an antimicrobial drug that kills a defined proportion of the original bacterial population (at least 99.9%).

Disk Diffusion (Kirby-Bauer)

Classifies susceptibility using zone diameter.

Muller-Hinton Agar medium is inoculated with a microorganism → antimicrobial discs are placed on the surface → incubate → measure the diameter → Resistant, Intermediate, Susceptible.

E Test

Uses an antibiotic gradient strip to estimate the MIC, read from the scale at the point where the edge of the inhibition ellipse intersects the strip.

Genetic Tests

Detect specific resistance genes but cannot rule out all other resistance mechanisms or directly provide an MIC.

Beta-lactamase

Enzymes that can inactivate beta-lactam antibiotics by opening their beta-lactam ring.

Antibiogram

A report of antimicrobial population-level susceptibility patterns in a healthcare institution.

How does resistance develop?

1. Antibiotic Exposure

2. Resistant Bacteria Survive

3. Natural Selection

4. Resistant Population Increases

Vertical Gene Transmission

Genetic mutation is already present → Binary fission → Offspring inherit the resistance trait.

Horizontal Gene Transfer

• Conjugation: DNA is transferred via cell-to-cell contact.

• Transduction: Bacteriophage transfers DNA from one cell to another.

• Transformation: Bacterium takes up DNA from environment.

Resistance genes may be carried on through the following:

• Plasmids: Small independent DNA molecule that can carry resistance genes.

• Transposons: DNA segments that can move from one location to another within DNA molecules.

Enzymatic Destruction or Inactivation

Bacteria produce enzymes that destroy or chemically modify the antibiotic, making it ineffective.

Prevention of Drug Entry:

Changes in the bacterial envelope or porin channels prevent sufficient antibiotic from entering the cell.

Alteration of the Drug's Target Site

The antibiotic can no longer bind effectively to its target, so the bacterium continues functioning.

Active Efflux

Membrane proteins pump the antibiotic out of the cell before it can reach an effective concentration.

Superbugs

Microorganisms resistant to multiple antimicrobial drugs.

Important examples include:

• MRSA

• Acinetobacter Baumannii

• Pseudomonas Aeruginosa

• Enterobacteriaceae

Therapeutic Benefit

The drug reaches a level sufficient to treat the infection.

Polymyxin B

Binds to the gram-negative outer membrane and disrupts membrane integrity.

Polymyxin E (Colistin)

Disrupts gram-negative bacterial membranes.

Triclosan

Inhibits bacterial fatty acid synthesis.

Isoniazid

Inhibits mycolic acid synthesis.

Potential Toxicity

The drug may cause harmful effects if its concentration, exposure, or individual susceptibility creates excessive risk.

Synergism

Drugs work together to enhance the effect.

Antagonism

One drug interferes with another drug's effect.

Childhood Development

Children may respond differently to medications than adults, and certain antibiotics can affect their development.

(i.e., Tetracyclines and permanent tooth discoloration).

Side Effect

An unintended effect of a medication that occurs in addition to its desired therapeutic effect.

Toxicity

The capacity of a substance to cause harm.

Hypersensitivity Reaction

An excessive or inappropriate immune response to a substance, including a medication.

Drug Interaction

A situation in which one drug changes the effect, concentration, or toxicity of another.

Therapeutic Index

A measure of the relationship between a drug's effective dose and its toxic dose.

Contraindication

A condition or circumstance in which a particular treatment should not be used, or should be used only under specific precautions.

Genome

The complete genetic information of a cell, including its chromosomes and plasmids.

Genomics

The study and sequencing of genomes

Chromosome

A DNA structure that carries hereditary information.

Gene

A segment of DNA that encodes a functional product, usually a protein or a functional RNA molecule.

Gene Expression

The process by which information in a gene is used to produce a functional product.

Central Dogma- the central dogma describes the usual flow of genetic information:

• DNA: Stores hereditary information.

• mRNA: Transcription- DNA information is copied into RNA.

• Protein: Translation- RNA information is decoded into an amino acid chain.

• Cellular Function: Metabolism, structure, growth, and other activities.

Inducible Operon

Usually switched on when a specific inducer is present. It commonly controls pathways for catabolism.

Repressible Operon

Usually active but switched off when a particular corepressor or end product is present. It commonly controls pathways for anabolism.

______________________ determines a cell's potential characteristics, but ______________________ determines when and how that information is expressed.

Genetic Information; Gene Regulation

DNA is composed of repeating units called nucleotides, each containing:

• Nitrogenous Base:

  • Adenine (A)

  • Thymine (T)

  • Cytosine (C)

  • Guanine (G)

• Deoxyribose Sugar

• Phosphate Group

A–T pairs through _________ bonds.

Double (2 Hydrogen)

C–G pairs through _________ bonds.

Triple (3 Hydrogen)

The strands are complementary and antiparallel:

One strand’s base sequence determines the other.

The base sequence stores genetic information.

Complementary base pairing allows DNA to copy itself accurately.

Genetic Code

The rules by which nucleotide sequences determine amino acid sequences in proteins.

Bacterial genomes may also contain plasmids, _________________________________________________________.

Small DNA molecules that replicate independently of the chromosome.

Short Tandem Repeats (STRs)

Repeated sequences of 2–5 bases that can be used in genetic identification and testing.

Open Reading Frame (ORF)

A DNA region potentially encoding a protein, generally identified by its start and stop codons.

Genotype

Genetic information an organism possesses.

Represents genetic potential. Includes genes that may or may not be active.

Phenotype

Characteristics that are physically expressed and observable.

Represents the observable or functional result. Depends on gene expression and other influences.

Replication- Vertical Gene Transfer

DNA is copied before cell division. Each daughter cell receives a chromosome derived from the parent cell.

Recombination- Horizontal Gene Transfer

Genetic material is acquired or exchanged between cells, creating new combinations of genes.

Replication is ____________________: each daughter DNA molecule contains one original parental strand and one newly synthesized strand.

Semiconservative

Why is semiconservative replication important?

Each original DNA strand serves as a template for the synthesis of a complementary strand. This preserves the original genetic information and supports accurate inheritance during cell division.