Microbiology Exam 4 Ch 20 Study Guide

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Antimicrobial Drugs

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Act by killing or by interfering with the growth of microorganisms.
Must act within the host within the host without damaging the host (selective toxicity)

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Antibiotic

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A substance produced by microorganisms that in small amounts inhibits another microorganism

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Sources of Antibiotics: Gram Positive

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Bacitracin
Polymyxin

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Bacillus subtilis

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Produces Bacitracin
gram-positive rods

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Paenibacillus Polymyxa

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Produces Polymyxin
gram-positive rods

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Sources of antibiotics: Actinomycetes

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Amphotericin B
Chloramphenicol
Chlortetracycline and tetracycline
Erythromycin
Neomycin
Streptomycin
Gentamicin

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Actinomycetes: Streptomyces nodosus

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Amphotericin B

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Actinomycetes: Streptomycems venezuelae

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Chloramphenicol

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Actinomycetes: Streptomycems aureofaciens (X2)

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Chlortetracycline and tetracycline

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Actinomycetes: Saccharopolyspora erythraea

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Erythromycin

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Actinomycetes: Streptomyces Fradiae

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Neomycin

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Actinomycetes: Streptomyces griseus

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Streptomycin

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Actinomycetes: Micromono purpurea

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Gentamicin

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Sources of Antibiotics: Fungi

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Cephalothin
Griseofulvin
Penicillin

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Fungi: Cephalpsporium spp.

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Cephalothin

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Fungi: Penicillium griseofulvum

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Griseofulvin

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Fungi: Penicillium chrysogenum

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Penicillin

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Spectrum of Antimicrobial Activity

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The range of different microbes that antibiotic will affect..

Broad spectrum or Narrow Spectrum

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Narrow Spectrum

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Affect a small range of bacteria. Ex. Penicillin G affects gram-positive bacteria but very few gram negative bacteria

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Broad Spectrum

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Affect a broad range of gram-positive or gram-negative bacteria.
Advantage: saves time because it affects a wide range
Disadvantage: Attacks some normal microbiota

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Superinfection

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The antibiotic does do destroy certain organisms in the normal microbiota but does destroy their competitors. the survivor may flourish and become an opportunistic pathogen..the overgrowth is called a superinfection

Ex. Candida albicans which is not sensitive to bacterial antibiotics

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Bactericidal

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Kills microbes directly

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Bacteriostatic

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Prevents the growth of microbes

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What are the major modes of action of Antimicrobial Drugs? (5 Modes)

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1) Inhibition of cell wall synthesis: penicillins, cephalosporins, bacitracin, vancomycin
2) Inhibition of protein synthesis: chloramphenicol, erythromycin, tetracyclines, streptomycin
3) Inhibition of nucleic acid replication and transcription, quinolones, rifampin
4) Injury to plasma membrane: polymyxin B
5) Inhibition of synthesis of essential metabolites: sulfanilamidem trimethoprin

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Modes of Action: Inhibiting Cell Wall Synthesis

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This includes Penicillins, cephalosporins, bacitracin, vancomycin.
Peptidoglycan is found in bacterial cell walls. Antibiotics prevent the synthesis of of intact peptidoglycan. The weakened cell walls are greatly weakened and the cel undergoes lysis. Only active growing cells are affected. Because human cells DO NOT have peptidoglycan cells walls, penicillin has very little toxicity to humans

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Modes of Action: 2) Inhibition of protein synthesis

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prokaryotes and eukayotes vary in the structure of their ribisomes. Euk. cells have 80S ribosomes and Prok. cells have 70S ribsomes. the S is for Svedberg units, the rate of sedimentation)
The difference accounts for the selective toxicity. However, Euk. mitochondria also have 70S. So, Antibiotics inhibiting protein synthesis, can adversely affect mitochondria.
Ex. chloramphenicol, erythromicin, streptomycin, tetracyclines

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Modes of Action: 3) Inhibiting Nucleic Acid synthesis

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Interfere with the processes of DNA replication and transcription.
Limited usefulness because they interfere with mammalian DNA as well

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Modes of Action: 4) Injuring the plasma membrane

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Especially polypeptide antibiotics, bring about changes in permeability.
Some drugs combine with sterols in the fungal plasma
membrane to disrupt the membrane.
Because bacterial plasma membranes lack sterols, there are ineffective
Ex. amphotericin B, miconazole, and ketoconazole

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Modes of Action: 5) Inhibiting the Synthesis of Essential Metabolites

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An organism can be competitively inhibited by a substance (antimetabolite) that closely resembles the normal substrate for the enzyme.
Ex. Relationship between antmetabolite sulfanilamide (a sulfa drug) and para amino benzoic acid (PABA). PABA is the substrate for an enzymatic reaction leading to the synthesis of folic acid. a vitamin that functions as a coenzyme for the synthesis of the purine and pyrimidine bases of nucleic acids and many amino acids

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Natural Penicillins: Penicillin G
(Inhibitor of Cell Wall Synthesis)

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The prototype compound of all Penicillins.
It has a narrow but useful spectrum of activity and is often the drug of choice against most staphylococci, streptococci, and several spirochetes.
rapidly exerted within 3-6 hours when injected intramuscularly.
When taken orally, stomach juices lower its potency.
Longer retention times can be accomplished with mixtures
1) Procaine penicillin: remains 24 hours, peaks at 4 hours
2) Benzathine penicillin: up to 4 months, but potency is low

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Natural Penicillins: Penicillin V
(Inhibitor of Cell Wall Synthesis)

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Stable to stomach acid so it can be taken orally.

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Penicillins
(Inhibitor of Cell Wall Synthesis)

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Have a core structure containing a B-lactam ring called the nucleus. The molecules are differentiated by the chemical side chains attached to their nuclei.
Can be produced naturally or artificially
They prevent the cross-linking of peptidoglycans, which interferes with cell wall construction, primarily with gram-positive bacteria

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Penicillinases

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Enzymes that are produced by many bacteria, most notably Staphylococcus species, cleaves the B-Lactam ring of the molecule

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Semisynthetic Penicillin
(Inhibitor of Cell Wall Synthesis)

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Developed to overcome disadvantages of Natural penicillins (narrow spectrum and susceptible to penicillinases)
Developed in two ways:
1) Interrupt synthesis of the molecule by Penicillin and obtain only the common penicillin nucleus for use
2) They can remove the side chains from the completed natural molecules and then chemically add other side chains that make then more resistant to Penicillinase, or the scientist give them an extended spectrum.
Part is the mold and part is added

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Penicillinase-resistant Penicillins

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Resistance to Staphylococcus infections became a problem because of plasmid borne gene for B-lactamase

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Semisynthetic Penicillins: Oxacillin
(Inhibitor of Cell Wall Synthesis)

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Resistant to penicillinase

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Semisynthetic Penicillins: Ampicillin
(Inhibitor of Cell Wall Synthesis)

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Broad Spectrum

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Semisynthetic Penicillins: Amoxicillin
(Inhibitor of Cell Wall Synthesis)

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Broad spectrum, combined with inhibitor of penicillinase

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Semisynthetic Penicillins: Aztreonam
(Inhibitor of Cell Wall Synthesis)

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A monobactam; effective for gram-negative bacteria including Pseudomonas spp.

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Semisynthetic Penicillins: Imipenem
(Inhibitor of Cell Wall Synthesis)

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A carbapenem; very broad spectrum

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Extended Spectrum Penicillins
(Inhibitor of Cell Wall Synthesis)

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effective against many gram-negative bacteria as well as gram-positive.
Are not resistant to penicillinase
Aminopenicillins: ampicillin and amoxicillin

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Penicillins plus B-Lactamase inhibitors
(Inhibitor of Cell Wall Synthesis)

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A different approach to the proliferation of penicillinase.
Combining penicillin with potassium clavulanate because it is a non-competitive inhibitor of penicillinase..further combined with broader spectrum penicillins such as amoxicillin (Aumentum)

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Carbapenems
(Inhibitor of Cell Wall Synthesis)

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Class of B-Lactam antibiotics that substitute a carbon atom for a sulfur atom and add a double bond to the penicillin nucleus. Inhibit cell wall synthesis have a broad spectrum. Ex. Primaxin

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Cephaloporins: Cephalothin
(Inhibitor of Cell Wall Synthesis)

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First generation cephalosporin; activity similar to penicillin. Effective against Gram positive bacteria.

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Cephaloporins
(Inhibitor of Cell Wall Synthesis)

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Inhibit cell wall synthesis. They are used more than any other B-Lactam antibiotic. The B-Lactam is slightly different from Penicillin
Bacteria have developed B-Lactamase that inactivates them
First generation are narow spectrum against gram positive bacteria

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Polypeptide Antibiotics: Bacitracin
(Inhibitor of Cell Wall Synthesis)

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Against gram Positive bacteria; topical application. Inhibits synthesis of cell walls

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Polypeptide Antibiotics: Vancomycin
(Inhibitor of Cell Wall Synthesis)

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A glycopeptide type; penicillinase-resistant; against gram-positive bacteria. Inhibits cell wall synthesis.

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Antimycobacterial Antibiotics: Isoniazid (INH)
(Inhibitor of Cell Wall Synthesis)

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Very effective against Tuberculous. Inhibit synthesis of cell wall acids (mycolic acids).

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Antimycobacterial Antibiotics:
(Inhibitor of Cell Wall Synthesis)

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The cell walls of Genus mycobacterium differ from most other bacteria (they stain acid fast). These include leprosy and tuberculosis

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Antimycobacterial Antibiotics: Chloramphenicol
(Inhibitor of Protein Syntesis)

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Broad spectrum; potentially toxic.
reacts with 50s portion of 70s prokaryotic ribosomes

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Aminoglycosides: Streptomycin

(Inhibitor of Protein Synthesis)

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Broad spectrum, including mycobacteria

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Aminoglycosides: Neomycin

(Inhibitor of Protein Synthesis)

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Topical use; broad spectrum

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Aminoglycosides:
(Inhibitor of Protein Synthesis)

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Interfere with Ribosome so that mRNA can't be read correctly. May have severe toxic effects such as hearing loss (due to damage to auditory nerve) and damage to kidneys

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Tetracycline:
(Inhibitor of Protein Synthesis)

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Effect the tRNA that carry the amino acids to the ribosomes. Effective against gram-positive and negative.
Can penetrate body tissues and and attack intracellular bacteria

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Tetracycline: Tetracycline

(Inhibitor of Protein Synthesis)

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Broad spectrum, including chlamydias and rickettias; animal feed additives

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Tetracycline: Oxytetracycline

(Inhibitor of Protein Synthesis)

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Broad spectrum, including chlamydias and rickettsias; animal feed additives.

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Macrolides:

(Inhibitor of Protein Synthesis)

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A group of drugs named for the presence of macrocyclic lactone ring which blocks the "tunnel" at the site of protein synthesis

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Macrolides: Erythomycin

(Inhibitor of Protein Synthesis)

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Alternative to penicillin

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Streptogramins: Quinupristin

(Inhibitor of Protein Synthesis)

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Alternative to treating with vancomycin-resistant gram positive bacteria

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Polymyxin
(Injury to the plasma membrane)

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Topical use, gram-negative bacteria, including Pseudomas spp

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Rifamycins: Rifampin

(Inhibitors of Nucleic Acid (DNA/RNA) synthesis)

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Inhibits synthesis of mRNA; treatment for tuberculosis

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Quinolones and Fluoroquinolones:

(Inhibitors of Nucleic Acid (DNA/RNA) synthesis)

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Bactericidal effect by release of enzyme inhibiting DNA gyrase, essential for replication of DNA

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Quinolones and Fluoroquinolones: Ciprofloxacin

(Inhibitors of Nucleic Acid (DNA/RNA) synthesis)

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Inhibit DNA synthesis; broad spectrum; urinary tract infection,

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Sulfonamides: Trimethoprim-sulfamethoxazole

(Competetive inhibitors of the synthesis of essential metabolites)

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Broad spectrum; combination is widely used.

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Antiviral drugs: Nucleoside and Nucleotide analogs

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Inhibit DNA and RNA synthesis or as a competitive inhibitor for HBV reverse transcriptase.

Effective against: Herpes, small pox, lamivudine

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Antiviral Drugs: Interferon

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Inhibits spread of virus to new cells. Ex: viral hepatitis