期刊论文详细信息
BMC Microbiology
Inhibition of Pseudomonas aeruginosa with a recombinant RNA-based viral vector expressing human β-defensin 4
Man-Seong Park1  Wook Chun3  Yong Suk Cho3  Jin-Won Song2  Hyung-Joo Kwon1  Mee Sook Park2  Hyejin Kim2  Seok-Il Jang1  Donghwan Kim1  Min-Woong Hwang1  Joon-Yong Bae1  Ilseob Lee1  Jin Il Kim1  Sehee Park1 
[1] Department of Microbiology, College of Medicine, Hallym University, Chuncheon 200-702, Gangwon-do, Republic of Korea;Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul 136-705, Republic of Korea;Department of Burn Surgery, Burn Center, Hangang Sacred Heart Hospital, Hallym University Medical Center, Seoul 150-719, Republic of Korea
关键词: Pseudomonas aeruginosa;    Newcastle disease virus;    Human ?-defensin;    Burn wounds;   
Others  :  1170525
DOI  :  10.1186/s12866-014-0237-z
 received in 2013-10-15, accepted in 2014-08-22,  发布年份 2014
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【 摘 要 】

Background

Harassed with extensive epithelial burn wounds, patients can be affected by complications, such as infection, hypovolemic shock, hypothermia, and respiratory failure. Immediate first aid and followed supportive cares are critical for the prevention of severe complications. However, secondary bacterial infection is hard to be controlled in burn patients, and Pseudomonas aeruginosa (P. aeruginosa) is one of the top listed pathogens perturbing burn wounds beyond the antibiotics spectrum.

Results

To find the way for efficacious protection from the pseudomonas-mediated complications in burn patients, we assessed the in vitro and in vivo inhibitory values of human ?-defensin 4 (hBD4), which is known as a member of the cationic, antimicrobial peptides found in human cells of many kinds. The Newcastle disease virus (NDV) was used as a viral vector for the expression of hBD4 in burn wounds. Expressed from the recombinant NDV (rNDV-hBD4), hBD4 effectively inhibited the pseudomonal growths in cell culture media. In a mouse model, severely burn-injured skin was recovered by the direct installation of the rNDV-hBD4 infected cells in the burn wounds whereas that of control mice remained severely damaged.

Conclusions

We suggest that the application of hBD4 may protect burn patients from secondary pseudomonal infection and provide a therapeutic potential for burn wound treatment.

【 授权许可】

   
2014 Park et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1][http://www.ameriburn.org/resources_factsheet.php] webcite American Burn Association: Burn incidence and treatment in the US: 2013 Fact Sheet..
  • [2][http://emergency.cdc.gov/masscasulaties/burns.asp] webcite Centers for Disease Control and Prevention (CDC): Emergency preparedness and response. Mass casualties: Burns..
  • [3]Church D, Elsayed S, Reid O, Winston B, Lindsay R: Burn wound infections. Clin Microbiol Rev 2006, 19(2):403-434.
  • [4]Guggenheim M, Zbinden R, Handschin AE, Gohritz A, Altintas MA, Giovanoli P: Changes in bacterial isolates from burn wounds and their antibiograms: a 20-year study (1986-2005). Burns 2009, 35(4):553-560.
  • [5]Singer AJ, McClain SA: Persistent wound infection delays epidermal maturation and increases scarring in thermal burns. Wound Repair Regen 2002, 10(6):372-377.
  • [6]Fitzwater J, Purdue GF, Hunt JL, O¿Keefe GE: The risk factors and time course of sepsis and organ dysfunction after burn trauma. J Trauma 2003, 54(5):959-966.
  • [7]Torpy JM, Lynm C, Glass RM: JAMA patient page. Burn injuries. JAMA 2009, 302(16):1828.
  • [8][http://www.who.int/surgery/publications/en/SCDH.pdf] webcite WHO: Surgical care at district hospital: 5.3 Burns. Accessed through .
  • [9]Brown TP, Cancio LC, McManus AT, Mason AD Jr: Survival benefit conferred by topical antimicrobial preparations in burn patients: a historical perspective. J Trauma 2004, 56(4):863-866.
  • [10]Altoparlak U, Erol S, Akcay MN, Celebi F, Kadanali A: The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 2004, 30(7):660-664.
  • [11]Ergun O, Celik A, Ergun G, Ozok G: Prophylactic antibiotic use in pediatric burn units. Eur J Pediatr Surg 2004, 14(6):422-426.
  • [12]Rafla K, Tredget EE: Infection control in the burn unit. Burns 2011, 37(1):5-15.
  • [13]Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI: Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 1985, 76(4):1427-1435.
  • [14]Menendez A, Brett Finlay B: Defensins in the immunology of bacterial infections. Curr Opin Immunol 2007, 19(4):385-391.
  • [15]Garcia JR, Krause A, Schulz S, Rodriguez-Jimenez FJ, Kluver E, Adermann K, Forssmann U, Frimpong-Boateng A, Bals R, Forssmann WG: Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. Faseb J 2001, 15(10):1819-1821.
  • [16]Supp DM, Gardner J, Klingenberg JM, Neely AN: Antibiotic resistance in clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus does not impact sensitivity to human beta defensin 4. Burns 2009, 35(7):949-955.
  • [17]Smiley AK, Gardner J, Klingenberg JM, Neely AN, Supp DM: Expression of human beta defensin 4 in genetically modified keratinocytes enhances antimicrobial activity. J Burn Care Res 2007, 28(1):127-132.
  • [18]Wei Q, Kim YS, Seo JH, Jang WS, Lee IH, Cha HJ: Facilitation of expression and purification of an antimicrobial peptide by fusion with baculoviral polyhedrin in Escherichia coli. Appl Environ Microbiol 2005, 71(9):5038-5043.
  • [19]Suzuki Y, Inokuchi S, Takazawa K, Umezawa K, Saito T, Kidokoro M, Tanaka M, Matsuzawa H, Inoue S, Tuchiya I, Ando K: Introduction of human beta-defensin-3 into cultured human keratinocytes and fibroblasts by infection of a recombinant adenovirus vector. Burns 2011, 37(1):109-116.
  • [20]Benihoud K, Yeh P, Perricaudet M: Adenovirus vectors for gene delivery. Curr Opin Biotechnol 1999, 10(5):440-447.
  • [21]Yang Y, Li Q, Ertl HC, Wilson JM: Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 1995, 69(4):2004-2015.
  • [22]McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, Janes H, Defawe OD, Carter DK, Hural J, Akondy R, Buchbinder SP, Robertson MN, Mehrotra DV, Self SG, Corey L, Shiver JW, Casimiro DR: HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 2008, 372(9653):1894-1905.
  • [23]Zamarin D, Vigil A, Kelly K, Garcia-Sastre A, Fong Y: Genetically engineered Newcastle disease virus for malignant melanoma therapy. Gene Ther 2009, 16(6):796-804.
  • [24]Park MS, Steel J, Garcia-Sastre A, Swayne D, Palese P: Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc Natl Acad Sci U S A 2006, 103(21):8203-8208.
  • [25]Schmidt CS, White CJ, Ibrahim AS, Filler SG, Fu Y, Yeaman MR, Edwards JE Jr, Hennessey JP Jr: NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. Vaccine 2012, 30(52):7594-7600.
  • [26]Gao Q, Park MS, Palese P: Expression of transgenes from newcastle disease virus with a segmented genome. J Virol 2008, 82(6):2692-2698.
  • [27]Nakaya T, Cros J, Park MS, Nakaya Y, Zheng H, Sagrera A, Villar E, Garcia-Sastre A, Palese P: Recombinant Newcastle disease virus as a vaccine vector. J Virol 2001, 75(23):11868-11873.
  • [28]Niyonsaba F, Ogawa H: Protective roles of the skin against infection: implication of naturally occurring human antimicrobial agents beta-defensins, cathelicidin LL-37 and lysozyme. J Dermatol Sci 2005, 40(3):157-168.
  • [29]Smyth MJ, Hayakawa Y, Takeda K, Yagita H: New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2002, 2(11):850-861.
  • [30]Nusbaum AG, Gil J, Rippy MK, Warne B, Valdes J, Claro A, Davis SC: Effective method to remove wound bacteria: comparison of various debridement modalities in an in vivo porcine model. J Surg Res 2012, 176(2):701-707.
  • [31]Deitch EA, Dobke M, Baxter CR: Failure of local immunity. A potential cause of burn wound sepsis. Arch Surg 1985, 120(1):78-84.
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