Alternative Approaches to Antimicrobial Therapy

Alternative Approaches to Antimicrobial Therapy

Alternative Approaches to Antimicrobial Therapy

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Phage Therapy & Lysins - Viral Vendetta

  • Phage Therapy: Uses bacteriophages (bacteria-specific viruses) to treat bacterial infections.

    • Mechanism: Lytic phages attach, inject genetic material, replicate within, and lyse the host bacterium.
    • Pros: High specificity (spares normal flora), self-replicating at infection site, effective vs. MDR strains, good biofilm penetration.
    • Cons: Narrow host range (precise matching essential), potential immune response, endotoxin release (lysed Gram-negatives).
    • Targets: P. aeruginosa, MRSA, A. baumannii, pathogenic E. coli.
  • Lysins (Endolysins): Phage-derived enzymes that degrade bacterial cell walls (peptidoglycan).

    • Mechanism: Act rapidly externally, causing lysis on contact.
    • Pros: Swift bactericidal action, broad lytic spectrum (esp. Gram+; Gram- may need permeabilizers), low resistance, anti-biofilm.
    • Cons: Potential immunogenicity, challenges in systemic delivery.
    • Example: Artilysins (engineered lysins).

⭐ Phages co-evolve with bacterial hosts, overcoming emerging resistance-a key advantage over static antibiotics.

Bacteriophage lytic cycle and lysin action

Antimicrobial Peptides & Antibodies - Protein Protectors

  • Antimicrobial Peptides (AMPs) / Host Defense Peptides (HDPs)
    • Cationic, amphipathic molecules; part of innate immunity.
    • Mechanism: Primarily disrupt microbial cell membranes (pore formation); also immunomodulatory.
    • Examples: Defensins, Cathelicidin (LL-37), Colistin (Polymyxin E for MDR Gram-negatives).
    • Pros: Broad-spectrum, rapid bactericidal action, low resistance development.
    • Cons: Potential systemic toxicity, stability issues, production cost.
  • Monoclonal Antibodies (mAbs)
    • Engineered antibodies targeting specific microbial antigens or toxins with precision.
    • Mechanism: Neutralize toxins/virulence factors, block pathogen entry, enhance opsonophagocytosis, ADCC (Antibody-Dependent Cell-mediated Cytotoxicity).
    • Examples:
      • Palivizumab (RSV F-protein; prophylaxis in high-risk infants).
      • Bezlotoxumab (Clostridioides difficile toxin B; prevents recurrence).
      • Raxibacumab (Anthrax protective antigen).
    • Pros: High specificity, long half-life, reduced off-target effects.
    • Cons: Narrow spectrum, high cost, parenteral administration.

⭐ Palivizumab, a humanized mAb, targets RSV F-protein for prophylaxis against severe RSV disease in high-risk pediatric groups.

Alternative antimicrobial therapies for bacteria

Anti-Virulence & Microbiome - Eco-Tactics

  • Anti-Virulence Therapy: Targets virulence (toxins, adhesins, QS), not growth. Disarms pathogens; ↓ resistance pressure.
    • Quorum Sensing Inhibitors (QSIs): Block bacterial signals; disrupt coordinated virulence (e.g., biofilms, toxin production).
    • Anti-Toxin Agents: Neutralize toxins (e.g., MABs for C. diff toxins A/B); reduce toxin-mediated damage.
    • Adhesion/Biofilm Blockers: Prevent pathogen attachment to host; disrupt protective microbial communities (biofilms).
  • Microbiome Modulation (Eco-Tactics): Restore/enhance protective host microbiota against pathogens.
    • Probiotics: Live beneficial microbes (e.g., Lactobacillus, Bifidobacterium) to improve gut balance.
    • Prebiotics: Non-digestible fibers (e.g., FOS, GOS) fueling beneficial gut bacteria.
    • Synbiotics: Synergistic Probiotics + Prebiotics.
    • Fecal Microbiota Transplantation (FMT): For recurrent C. difficile (rCDI); restores healthy gut flora.
    • Phage Therapy: Bacteriophages specifically lyse pathogenic bacteria; re-emerging precision tool. 📌 Phages Phight Pests!

⭐ FMT shows >90% efficacy for recurrent Clostridioides difficile infection (rCDI), a major AMR concern.

Alternative approaches to antimicrobial therapy

High‑Yield Points - ⚡ Biggest Takeaways

  • Phage therapy uses bacteriophages for specific bacterial lysis, bypassing resistance.
  • Antimicrobial peptides (AMPs) offer broad-spectrum action via novel mechanisms from innate immunity.
  • Monoclonal antibodies (mAbs) neutralize specific virulence factors or bacterial components.
  • Probiotics and prebiotics modulate gut microbiota, enhancing host defense mechanisms.
  • Vaccines are crucial for preventing infections, thereby reducing antimicrobial dependency.
  • Quorum Sensing Inhibitors (QSIs) disrupt bacterial communication and virulence factor expression.
  • CRISPR-Cas based antimicrobials can target resistance genes or achieve specific bacterial killing.
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Practice Questions: Alternative Approaches to Antimicrobial Therapy

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Which of the following bacteria can be identified using phage typing?

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_____ is the molecular basis of penicillin G resistance in pneumococci and meningococci.

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_____ is the molecular basis of penicillin G resistance in pneumococci and meningococci.

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Alternative Approaches to Antimicrobial Therapy | Antimicrobial Resistance - OnCourse NEET-PG