Bacteriology lecture 6

Question 1

Antimicrobial agent/drug

Answer 1

Chemical substance used to treat diseases caused
by pathogenic microbes

Question 2

Antibiotic

Answer 2

Chemical substance (/drug) produced by microorganisms, with the capacity to control growth/kill microbes. They can be Bacteriostatic or bacteriocidal, Synthetic or natural product (bacteria/fungi)

Question 3

Properties of Useful Chemotherapeutic Agents

Answer 3

• Selectively toxic to pathogens; non-toxic to host and minimal effect on normal microbial flora – determine chemotherapeutic index
• Should not stimulate an allergic reaction (hypersensitivity)
• Host should not destroy or neutralise drug before effective
• Pathogens should not easily become resistant to the drug
• Agent should reach the site of infection (solubility)

Question 4

The Spectrum of Antimicrobial Agents

Answer 4

Spectrum of activity: Range of different microorganisms treatable with an agent

• Broad spectrum: Active across a wide range of taxonomic groups; useful for untargeted treatment without pathogen identification
• Narrow spectrum: Specifically targets small number of organisms; may protect host microflora; reduces development of drug resistance

Question 5

Mechanisms of Antimicrobial Agent Activity

Answer 5

• Inhibition of Cell Wall Synthesis
  – Disruption of Cell Membrane Function
  – Inhibition of Protein Synthesis
  – Inhibition of Nucleic Acid Synthesis
  – Action as Antimetabolites

Question 5

Mechanisms of Antimicrobial Agent Activity

Answer 5

• Inhibition of Cell Wall Synthesis
  – Disruption of Cell Membrane Function
  – Inhibition of Protein Synthesis
  – Inhibition of Nucleic Acid Synthesis
  – Action as Antimetabolites

Question 6

Inhibition of Cell Wall Synthesis

Answer 6

• Penicillins: Bactericidal; All contain a β-lactam ring; Natural penicillins (G, V) are penicillinase sensitive and narrow spectrum. Semi-synthetic penicillins are modified to increase penicillinase resistance and broaden spectrum (e.g.methicillin, ampicillin, amoxicillin)
• Cephalosporins: Effective against more Gram-negatives; Resistant to Penicillinases; More expensive; Mainly IV/IM
• Bacitracin: Polypeptide antibiotic; Effective against Gram positives; Topical application
• Vancomycin: Glycopeptide antibiotics; narrow spectrum; toxic; Penicillinase-resistant

Question 7

Disruption of Cell Membrane Function

Answer 7

Alter permeability of bacterial cell membranes; Polypeptide antibiotics; clinical application limited to certain members due to similarities between host and bacterial cell membranes
* Polymyxins: (A, B, C, D, E) used only when pathogen is resistant to other less toxic antibiotics; Gram negatives; Topical
* Nystatin: combine with sterols; therefore effective against mycoplasmas (and also systemic fungal infections).
* Colicins: Bacteriocin of E.coli; encoded by Col plasmid, which also codes for immunity protein. Kills bacterial cells not carrying the plasmid e.g. cells of same species.

Question 8

Inhibition of Protein Synthesis

Answer 8

Takes advantage of differences between bacterial and eukaryotic ribosomes – selective toxicity

Question 9

Inhibition of Protein Synthesis: Aminoglycosides

Answer 9

Amino sugars linked by glycoside bonds. Broad spectrum. Bacteriocidal; bacteriostatic at lower doses. Work synergistically with other compounds (e.g. penicillin) Streptomycin (1940s); now has high resistance levels; toxic. Other compounds (kanamycin, gentamicin etc.)

Question 10

Inhibition of Protein Synthesis: Chloramphenicol

Answer 10

Bacteriostatic; Broad Spectrum; Inhibits peptide bond formation. Damages bone marrow

Question 11

Inhibition of Protein Synthesis: Tetracyclines

Answer 11

Interfere with tRNA attachment. Bacteriostatic; very broad spectrum; can inhibit intestinal microflora

Question 12

Inhibition of Protein Synthesis: Macrolides

Answer 12

Erythromycin – Bacteriostatic. Can not penetrate Gram negative cell walls. Used as an alternative to Penicillin

Question 13

Inhibition of Nucleic Acid Synthesis

Answer 13

Can be Toxic to host cells due to common targets

• Rifampin: Inhibits mRNA synthesis by binding RNA polymerase; High absorbance into tissues and cells; Bactericidal; Broad Spectrum; Interacts with other drugs; Treatment of mycobacteria infections-leprosy and tuberculosis
• Quinolones: Blocks bacterial enzyme that unwinds DNA prior to replication; Broad spectrum; Used for UTIs; Can affect cartilage development

Question 14

Action as Antimetabolites

Answer 14

Compounds that interfere with metabolic reactions by:
1) Competitive inhibition of enzymes or
2) Erroneous incorporation into important molecules

Antimetabolites are structurally similar to normal metabolites – molecular mimicry

Question 14

Action as Antimetabolites

Answer 14

Compounds that interfere with metabolic reactions by:
1) Competitive inhibition of enzymes or
2) Erroneous incorporation into important molecules

Antimetabolites are structurally similar to normal metabolites – molecular mimicry

Question 15

Competitive Inhibition:

Answer 15

• Bacterial cells require PABA to make folic acid (for synthesis of nitrogenous bases in DNA). This process is inhibited by sulphonamides or PAS.
• Animal cells lack enzyme that makes folic acid so does not affect animal cell metabolism
• Sulfonamides: Bacteriostatic; Oral administration

Question 15

Competitive Inhibition:

Answer 15

• Bacterial cells require PABA to make folic acid (for synthesis of nitrogenous bases in DNA). This process is inhibited by sulphonamides or PAS.
• Animal cells lack enzyme that makes folic acid so does not affect animal cell metabolism
• Sulfonamides: Bacteriostatic; Oral administration

Question 16

Erroneous incorporation:

Answer 16

Vidarabine and Idouridine are incorporated into DNA and can block replication and transcription due to disruption of base-pairing.
Host toxicity = Bacterial toxicity (Mainly used to treat viral infections)

Question 17

Toxicity

Answer 17

Action of antimicrobial also alters some process within the host.
- Teeth staining from tetracycline: Sequesters Calcium
- ‘Red (wo)man’ syndrome from Rifampin: Byproduct accumulates under skin

Question 18

Allergy

Answer 18

• Body can produce an allergic reaction to some antibiotics
• Immune system recognises compound as foreign and initiates a reaction – can range from mild to severe
• Example: Penicillin – breakdown product combines with proteins in the body fluid to form a molecule which can be treated as a threat by the immune system (often IgE-mediated)
• Penicillin allergy reported by ~10% of patients but only confirmed in 1% of the population1

Question 19

Disruptionofnormalmicroflora

Answer 19

• Broad spectrum antimicrobials can deplete normal microflora in addition to pathogenic targets.
• Less growth competition allows opportunistic/resistant pathogens to flourish
• Superinfection: Replacement of normal microflora by an invading organism (E.g. Candida yeast); Can be difficult to treat due to resistance