MIC102 S10 - Human microbiota and antibiotics

Describe the (a)cellular community members of the human microbiota

Acellular

• Viruses, especially bacteriopahges

• Eukaryotic viruses

Cellular

• Bacteria (main)

• Archaea

• Fungi

• Protozoa

Examples of key functions and factors that influence gut microbiota

• geographical location

• host genetics

• exercise

• mode of delivery

• diet

• gastric secretion

• antimicrobial peptides

• gastric motility

• age

• antibiotics

• stress

Describe the properties antibiotics can have (ex: broad vs. narrow spectrum, bacteriostatic v. bacteriocidal)

Spectrum

• Broad

  • target wide range of bacteria, both gram-negative and positive

  • useful when pathogen is unknown or in mixed infections

  • Ex: tetracyclines

• Narrow

  • target a specific group of bacteria

  • preferred when the pathogen is unknown to avoid killing beneficial microbiota

  • ex: penicillin G (gram-positive)

Effect on Bacteria

• Bacteriocidal

  • kill bacteria directly

  • Often used in sever or life-threatening infections, or when immune system is compromised (less able to fight disease)

  • Ex: penicillin

• Bacteriostatic

  • Inhibit bacterial growth, allow immune system to eliminate infection

  • Not ideal in immunocompromised patients

Other effects

• mechanism of action → target differnet parts of bacteria (ex: cell wall, ribosome)

• selective toxicity, route of administration, tissue penetration, resistance potential

Explain why bacterial cell wall synthesis, DNA replication, transcription, translation, and folate synthesis are good processes to target for antibiotics

Overarching theme → All of thee are good targets because they are unique to bacteria and don’t target eukaryotic cells which could potentially harm humans

Many of these processes target enzymes involved in these processes

List the steps in peptidoglycan synthesis and identify which steps/biosynthetic enzymes are antibiotic targets,

Steps

1) N-acetylglucosamine (G) and N-acetylmuramic acid (M) subunits are made

2) Pentapeptide built on M

3) Peptide-M linekd to lipid carrier

4) Peptide-M and G are linked

5) Lipid carrier with peptide-M-G is transported across cell membrane by a flippase

6_ Peptide-M-G added to glycan chain by a transclycosylase, releasing the lipid carrier

7) Peptide side chains cross-linked by a transpeptidase

Common Antibiotic Target

• Note: all of these steps cna be inhibited

• Common targets

  • Step 7: Inhibit linkage of peptide side chains by transpeptidase (ex: beta-lactams)

  • Inhibit the linakge of NAG-NAM disaccharide units by transglycosylase

  • Inhibit release of NAG-NAM0peptide form the lipid carier

Describe the mechanisms of antibiotic resistance and explain why resistant cells increase in frequency under selection by antibiotics

Antibiotic resistance mechanisms → initial source is the antibiotic producers → genes and systems bacteria use to protect themselves form anitbiotics evolved in bacteria for self-defense

Different mechanisms

• Efflux pump - efflux of antibiotic outside cell

• Target site modification - antibiotic don’t fit with target

• Target bypass - new protein with smae metabolic capacity as target

• Decreased influx - less abx allowed inside

• Down regulation of porins - less porins to allow abx inside

• Antibiotic inactivation

Frequency increase under abx selection

• Population of bacteria exposed to drug → most die except resistant mutant → remaining population grows over time

Identify health benefits and risks associated with antibiotic use.

Benefits

1) Cure bacterial diseases

2) Prevent Infection

3) Enable Modern medicine

4) Reduce Transmission

5) Microbiota can be replaced with probiotics and fecal transplants

Risks

1) Antibiotic resistance by harmful bacteria

2) Damage to Normal Microbiota (Dysbiosis)

3) Side effects and allergic reactions

Explain how the dysbiosis (e.g., after antibiotic treatment) can be mitigated and/or corrected.

Dysbiosis - Disruption of normal microbial community (especially in the gut)

Fixed by:

• Probiotics

  • live beneficial microbes → taken during or after to recolnize gut

• Prebiotics

  • Non-digestible dietary fibers that feed beneficial bacteria

• Fecal Microbiota Transplantation

• Dietary Support

• Targeted and Proper Antibiotic Use

• Post-Antibiotic recovery time

Identify what you personally can do to limit the rise of antibiotic resistance.

1) Use antibiotics only when needed and only against susceptible organisms

2) Follow prescriptions exactly

3) Prevent infections in the first place

4)Education