Identification and characterization of a mucosal antimicrobial peptide expressed by the chinchilla (Chinchilla lanigera) airway.
Cationic antimicrobial peptides (APs) are produced at mucosal surfaces and play a key role as a first line of defense against infection. To understand how APs might impact disease progression in otitis media (OM), our goal was to identify and characterize APs expressed by the epithelium lining the uppermost airway of the chinchilla, the established rodent host for the study of the bacterial-viral pathogenesis in OM. Using a molecular approach, we cloned a cDNA encoding a homolog of human beta-defensin 3, designated chinchilla beta-defensin-1 (cBD-1), and found by Northern analysis expression of the corresponding mRNA in nasopharyngeal and tongue mucosae as well as skin. By reverse transcription-PCR, cBD-1 mRNA was also detected in RNA isolated from trachea, lung, and Eustachian tube tissues. The predicted mature form of cBD-1, expressed as a recombinant peptide in Escherichia coli, demonstrated bactericidal activity against the three primary opportunistic pathogens of OM as well as Candida albicans. Continued study of this and other APs will allow us to determine their role in bacterial colonization of the upper airway as well as how viruses might contribute to the pathogenesis of OM by modulating AP expression.
Harris
Randall H
RH
Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus Children's Research Institute, Center for Microbial Pathogenesis, 700 Children's Drive, Columbus, OH 43205-2696, USA.
Wilk
Dennis
D
Bevins
Charles L
CL
Munson
Robert S
RS
Bakaletz
Lauren O
LO
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002176:Candida albicans / Q000378:metabolism; D002682:Chinchilla; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005064:Eustachian Tube / Q000378:metabolism; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D010033:Otitis Media / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013997:Time Factors; D014018:Tissue Distribution; D014059:Tongue / Q000473:pathology; D014132:Trachea / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics
D000900:Anti-Bacterial Agents; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; D018076:DNA, Complementary; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D023083:beta-Defensins; D012313:RNA