ArticleProceedings of the National Academy of Sciences of the United States of America2014
pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 202 citations in OpenAlex.
- Effects of Tham Nasal Alkalinization on Airway Microbial Communities: A Pilot Study in Non-CF and CF Adults.The Annals of otology, rhinology, and laryngology · 2022Trial
- Aggregation-State Dynamics Drive Double Cooperativity Between Antimicrobial Peptides LL-37 and HNP1.Angewandte Chemie (International ed. in English) · 2026Article
- Heteroaggregation of Antimicrobial Peptides LL-37 and HNP‑1 Drives Cooperative Neutralization of Cytotoxicity.JACS Au · 2026Article
- Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations.The Journal of membrane biology · 2026Article
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- APD6: the antimicrobial peptide database is expanded to promote research and development by deploying an unprecedented information pipeline.Nucleic acids research · 2026Article
- Microbiome dysbiosis and therapeutic restoration in atopic dermatitis.Frontiers in cellular and infection microbiology · 2026Review
- Molecular Prosthetics and CFTR Modulators Additively Increase Secretory HCOACS chemical biology · 2025Article
- Biological properties of ceragenin-coated metal nanoparticles - future challenges and perspectives in clinical practice.Nanomedicine (London, England) · 2025Review
- Immune system dynamics in response to Pseudomonas aeruginosa biofilms.NPJ biofilms and microbiomes · 2025Review
- Immune escape ofFrontiers in cellular and infection microbiology · 2025Review
- The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Ceragenins Prevent the Development of Murine Vaginal Infection Caused byPharmaceuticals (Basel, Switzerland) · 2024Article
- Pulmonary Ionocytes: What Are They Transporting and Which Way?American journal of respiratory and critical care medicine · 2024Article
- Storage stability of lysostaphin solution and its pulmonary delivery.Drug delivery and translational research · 2024Article
- The pH-Insensitive Antimicrobial and Antibiofilm Activities of the Frog Skin Derived Peptide Esc(1-21): Promising Features for Novel Anti-Infective Drugs.Antibiotics (Basel, Switzerland) · 2024Article
- Sex differences in airway disease: estrogen and airway surface liquid dynamics.Biology of sex differences · 2024Review
- Epithelial responses to CFTR modulators are improved by inflammatory cytokines and impaired by antiinflammatory drugs.JCI insight · 2024Article
- Cystic Fibrosis Carrier States Are Associated With More Severe Cases of Bronchiectasis.Open forum infectious diseases · 2024Article
- CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.Frontiers in physiology · 2024Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The pulmonary airways are continuously exposed to bacteria. As a first line of defense against infection, the airway surface liquid (ASL) contains a complex mixture of antimicrobial factors that kill inhaled and aspirated bacteria. The composition of ASL is critical for antimicrobial effectiveness. For example, in cystic fibrosis an abnormally acidic ASL inhibits antimicrobial activity. Here, we tested the effect of pH on the activity of an ASL defensin, human β-defensin-3 (hBD-3), and the cathelicidin-related peptide, LL-37. We found that reducing pH from 8.0 to 6.8 reduced the ability of both peptides to kill Staphylococcus aureus. An acidic pH also attenuated LL-37 killing of Pseudomonas aeruginosa. In addition, we discovered synergism between hBD-3 and LL-37 in killing S. aureus. LL-37 and lysozyme were also synergistic. Importantly, an acidic pH reduced the synergistic effects of combinations of ASL antibacterials. These results indicate that an acidic pH reduces the activity of individual ASL antimicrobials, impairs synergism between them, and thus may disrupt an important airway host defense mechanism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.