Inhibition of Multidrug-resistant Acinetobacter baumannii by Nonviral Expression of hCAP-18 in a Bioengineered Human Skin Tissue

• Published in: Molecular therapy Vol. 17; no. 3; pp. 562 - 569
• Main Authors: Thomas-Virnig, Christina L, Centanni, John M, Johnston, Colette E, He, Li-Ke, Schlosser, Sandy J, Van Winkle, Kelly F, Chen, Ruibing, Gibson, Angela L, Szilagyi, Andrea, Li, Lingjun, Shankar, Ravi, Allen-Hoffmann, B Lynn
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2009; Elsevier Limited; Nature Publishing Group
• Subjects: Acinetobacter baumannii - physiology; Animals; Antimicrobial agents; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - metabolism; Bacteria; Bacterial infections; Burns - genetics; Burns - microbiology; Burns - therapy; Cells, Cultured; Cloning; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gene Expression; Gene therapy; Genetic Therapy; Genetic Vectors - genetics; Humans; Infections; Keratinocytes - metabolism; Mice; Mice, Nude; Neurosciences; Original; Pathogens; Peptides; Protein Engineering - methods; Skin - metabolism; Tumors; Wound healing; United States > US; Wisconsin
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2008.289

When skin is compromised, a cascade of signals initiates the rapid repair of the epidermis to prevent fluid loss and provide defense against invading microbes. During this response, keratinocytes produce host defense peptides (HDPs) that have antimicrobial activity against a diverse set of pathogens. Using nonviral vectors we have genetically modified the novel, nontumorigenic, pathogen-free human keratinocyte progenitor cell line (NIKS) to express the human cathelicidin HDP in a tissue-specific manner. NIKS skin tissue that expresses elevated levels of cathelicidin possesses key histological features of normal epidermis and displays enhanced antimicrobial activity against bacteria in vitro. Moreover, in an in vivo infected burn wound model, this tissue results in a two log reduction in a clinical isolate of multidrug-resistant Acinetobacter baumannii. Taken together, these results suggest that this genetically engineered human tissue could be applied to burns and ulcers to counteract bacterial contamination and prevent infection.