Inhibition of multidrug-resistant Acinetobacter baumannii by nonviral expression of hCAP-18 in a bioengineered human skin tissue.
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.
Thomas-Virnig
Christina L
CL
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706-1102, USA.
Centanni
John M
JM
Johnston
Colette E
CE
He
Li-Ke
LK
Schlosser
Sandy J
SJ
Van Winkle
Kelly F
KF
Chen
Ruibing
R
Gibson
Angela L
AL
Szilagyi
Andrea
A
Li
Lingjun
L
Shankar
Ravi
R
Allen-Hoffmann
B Lynn
BL
D040981:Acinetobacter baumannii / Q000502:physiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D002056:Burns / Q000235:genetics / Q000382:microbiology / Q000628:therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015202:Protein Engineering / Q000379:methods*; D012867:Skin / Q000378:metabolism*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins