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Biofilm Formations in Pediatric Respiratory Tract Infection Part 2: Mucosal Biofilm Formation by Respiratory Pathogens and Current and Future Therapeutic Strategies to Inhibit Biofilm Formation or Eradicate Established Biofilm

  • Pediatric Infectious Diseases (I. Brook, Section Editor)
  • Published:
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Abstract

Purpose of Review

The purpose of this review is to discuss the unique pathways of biofilm formation utilized by respiratory pathogens and current and future therapeutic strategies to inhibit biofilm formation or eradicate established biofilm in the context of these pathogens. Both nonselective and selective strategies for inhibiting biofilm formation or disrupting established biofilm are discussed.

Recent Findings

Numerous strategies are being actively pursued to inhibit biofilm formation or eradicate established biofilm in respiratory pathogens. These can be broadly categorized by the stage of biofilm formation (adhesion, extracellular polysaccharide synthesis or structure, EPS, and matrix degradation) that they target and by their selectivity or lack thereof for specific biofilm pathogens. Nonselective inhibitors of adhesion include N-acetylcysteine and artificial surfactants and biosurfactants. Selective inhibitors of adhesion include mannosides that target host-EPS interactions, EPS-targeted antibodies, and other inhibitors of bacterial adhesion. Nonselective inhibitors of EPS synthesis and structure include cyclic di-GMP and cyclic di-AMP—through disruption of glucan-producing exoenzymes. Selective inhibitors of EPS synthesis and structure include antibodies that target proteins essential for biofilm structure (such as DNABII proteins and type IV pilin protein in NTHi) or antibodies that target critical molecules in biofilm formation (such as DNA adenine methyltransferase in Streptococcus pneumoniae). Nonselective agents for EPS or biofilm matrix degradation include peptidoglycan hydrolases that enzymatically degrade bacterial cell wall peptidoglycan and DNase, which degrades extracellular DNA from neutrophils and microorganism-derived DNA. Selective agents for EPS or biofilm matrix degradation include exopolysaccharide-degrading enzymes, such as glycoside hydrolases active against Staphylococcus aureus or exopolysaccharide-degrading enzymes that target Psl and Pel from Pseudomonas aeruginosa.

Summary

Current strategies toward inhibiting biofilm formation or disrupting established biofilm represent an exciting new approach toward treatment of chronic infectious diseases. Application of these strategies toward treatment of pediatric respiratory tract infections also offers promise of a better understanding of the significance of mucosal biofilm in the pathogenesis of these conditions.

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, 55 Fruit Street, Bulfinch-422, Boston, MA, 02114, USA

    Daniel L. Hamilos

  2. Harvard Medical School, Boston, MA, 02115, USA

    Daniel L. Hamilos

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Hamilos, D.L. Biofilm Formations in Pediatric Respiratory Tract Infection Part 2: Mucosal Biofilm Formation by Respiratory Pathogens and Current and Future Therapeutic Strategies to Inhibit Biofilm Formation or Eradicate Established Biofilm. Curr Infect Dis Rep 21, 8 (2019). https://doi.org/10.1007/s11908-019-0657-x

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