Journal article
pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37
Proceedings of the National Academy of Sciences - PNAS, Vol.111(52), pp.18703-18708
12/30/2014
DOI: 10.1073/pnas.1422091112
PMCID: PMC4284593
PMID: 25512526
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.
Details
- Title: Subtitle
- pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37
- Creators
- Mahmoud H Abou Alaiwa - Departments of Internal MedicineLeah R Reznikov - Departments of Internal MedicineNicholas D Gansemer - Departments of Internal MedicineKelsey A Sheets - Departments of Internal MedicineAlexander R Horswill - Microbiology, andDavid A Stoltz - Departments of Internal Medicine, Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, Department of Biomedical Engineering, andJoseph Zabner - Departments of Internal MedicineMichael J Welsh - Departments of Internal Medicine, Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242 michael-welsh@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(52), pp.18703-18708
- DOI
- 10.1073/pnas.1422091112
- PMID
- 25512526
- PMCID
- PMC4284593
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences; United States
- Grant note
- P01 HL091842 / NHLBI NIH HHS Howard Hughes Medical Institute HL091842 / NHLBI NIH HHS P01 HL051670 / NHLBI NIH HHS HL51670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS K99 HL119560 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/30/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020614402771
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