biostudies-literatureAbou Alaiwa MHHHS | National Institutes of Health (NIH)Howard Hughes Medical InstituteNIDDK NIH HHSNHLBI NIH HHSRoy J Carver Charitable TrustCystic Fibrosis Foundation (CFF)18703-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4284593biostudies-literatureUnknown111(52)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-37Proceedings of the National Academy of Sciences of the United States of AmericapH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37.PMC4284593IOWAHL091842P30 DK054759P01 HL091842K99 HL119560CF0086552P01 HL051670HL51670Abou Alaiwa MHWelsh MJSheets KAZabner JReznikov LRHorswill ARGansemer NDStoltz DAfalsepH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37.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-372014-01-01T00:00:00Z2014 Dec2025-04-04T22:04:12.137Z2019-03-27T01:42:46ZS-EPMC42845932551252610.1073/pnas.1422091112