JAC Advance Access published online on May 1, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn176
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Original research |
Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13
1 Department of Physiology, Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Research Laboratories, 3340 Smith Walk, Philadelphia, PA 19104, USA 2 Department of Prosthetic Dentistry, Medical University of Bialystok, 15-230 Bialystok, Poland 3 Department of Physiology, Medical University of Bialystok, 15-230 Bialystok, Poland 4 Department of Chemistry and Biochemistry, Brigham Young University, C-I00 BNSN, Provo, UT 84602, USA
Received 29 August 2007; returned 2 January 2008; revised 20 February 2008; accepted 29 March 2008
* Corresponding author. Tel: +1-215-573-9787; Fax: +1-215-573-7227; E-mail: buckirob{at}mail.med.upenn.edu
Objectives: Cationic antimicrobial peptides (CAPs) are the effector molecules of innate immunity, similar in potency to classic antibiotics that function in the first-line of defence against infectious agents. The purpose of this study was to investigate the effects of negatively charged mucins on the antibacterial activity of the positively charged cathelicidin LL-37 peptide, its synthetic analogue WLBU2 and the antimicrobial cationic steroid CSA-13.
Methods: Mucin, DNA, F-actin and hCAP-18/LL-37 in saliva samples were evaluated by microscopy or immunoblotting. Bacterial killing assays and determination of MICs were used to determine bactericidal activity. Binding of rhodamine-B-labelled LL-37 peptide to mucin was fluorimetrically assessed.
Results: Microscopic evaluation of saliva after addition of rhodamine-B-labelled LL-37 showed localization similar to that observed after the addition of a specific mucin-binding lectin. Immunoblotting confirmed the presence of hCAP-18/LL-37 in saliva samples and LL-37 peptide bound to isolated submaxillary gland mucin-coated plates. Mucin/LL-37 binding was partially prevented by treatment of mucin with neuraminidase, indicating involvement of sialic acid moieties. Decreased LL-37 and WLBU2 antibacterial activity was observed in the presence of mucin or dialysed human saliva, whereas CSA-13 antibacterial activity was significantly resistant to inhibition by mucins.
Conclusions: This study shows that the antibacterial LL-37 peptide and its synthetic analogue WLBU2 are inhibited by salivary mucin and that the cationic steroid CSA-13 retains most of its function in the presence of an equal amount of mucin or saliva.
Key Words: neuraminidase , hCAP-18 , antibacterial peptides , WLBU2
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