Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model.

作者: Jayaram Lakshmaiah Narayana , Han-Ning Huang , Chang-Jer Wu , Jyh-Yih Chen

DOI: 10.18632/ONCOTARGET.4101

关键词: BiologyMicrobiologyHelicobacter pyloriPathogenImmunologyMultiple drug resistanceGastritisImmune systemProinflammatory cytokineIn vivoAntibiotics

摘要: // Jayaram Lakshmaiah Narayana 1,2 , Han-Ning Huang 2 Chang-Jer Wu 3 and Jyh-Yih Chen 1 Doctoral Degree Program in Marine Biotechnology, Academia Sinica National Sun Yat-sen University, Kaohsiung, Taiwan Research Station, Institute of Cellular Orgasmic Biology, Sinica, Jiaushi, Ilan, Department Food Science, Ocean Keelung, Correspondence to: Chen, email: Wu, Keywords : Helicobacter pylori, antimicrobial peptide, tilapia piscidin 4 (TP4), micellization Received February 16, 2015 Accepted April 09, Published May 11, Abstract pylori infection is marked by a strong association with various gastric diseases, including gastritis, ulcers, cancer. Antibiotic treatment regimens have low success rates due to the rapid occurrence resistant H. strains, necessitating development novel anti- strategies. Here, we investigated therapeutic potential Tilapia Piscidin against multidrug pathogen based on its vitro vivo efficacy.TP4 inhibited growth both antibiotic-sensitive -resistant ( Cag A + Vac ) via membrane micelle formation, which led depolarization extravasation cellular constituents. During colonization tissue, maintains high T regulatorysubsets Th17/Treg ratio, results expression pro- anti-inflammatory cytokines. Treatment TP4 suppressed Treg subset populations inflammatory restored balance, resulted early clearance density recovery morphology. Toxicity studies demonstrated that has no adverse effects mice or rabbits. The this study indicate may be an effective safe monotherapeutic agent for infections.

参考文章(71)
Umaporn Silphaduang, Edward J. Noga, Peptide antibiotics in mast cells of fish Nature. ,vol. 414, pp. 268- 269 ,(2001) , 10.1038/35104690
R. John Dobbs, Sylvia M. Dobbs, Clive Weller, Ingua T. Bjarnason, Norman L. Oxlade, Andre Charlett, Mazin A. Al-Janabi, Robert W. Kerwin, Robert F. Mahler, Ashley B. Price, Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic Parkinsonism. Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism Helicobacter. ,vol. 10, pp. 267- 275 ,(2005) , 10.1111/J.1523-5378.2005.00331.X
R T Ellison, T J Giehl, F M LaForce, Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infection and Immunity. ,vol. 56, pp. 2774- 2781 ,(1988) , 10.1128/IAI.56.11.2774-2781.1988
David I. Chan, Elmar J. Prenner, Hans J. Vogel, Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action. Biochimica et Biophysica Acta. ,vol. 1758, pp. 1184- 1202 ,(2006) , 10.1016/J.BBAMEM.2006.04.006
Abraham Nomura, Grant N Stemmermann, Po-Huang Chyou, Guillermo I Perez-Perez, Martin J Blaser, Helicobacter pylori Infection and the Risk for Duodenal and Gastric Ulceration Annals of Internal Medicine. ,vol. 120, pp. 977- 981 ,(1994) , 10.7326/0003-4819-120-12-199406150-00001
Z Wang, C Friedrich, S C Hagemann, W H Korte, N Goharani, S Cording, G Eberl, T Sparwasser, M Lochner, Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. Mucosal Immunology. ,vol. 7, pp. 1290- 1301 ,(2014) , 10.1038/MI.2014.17
Pelayo Correa, JeanMarie Houghton, Carcinogenesis of Helicobacter pylori Gastroenterology. ,vol. 133, pp. 659- 672 ,(2007) , 10.1053/J.GASTRO.2007.06.026
Marisa L. Winkler, Krisztina M. Papp-Wallace, Andrea M. Hujer, T. Nicholas Domitrovic, Kristine M. Hujer, Kelly N. Hurless, Marion Tuohy, Geraldine Hall, Robert A. Bonomo, Unexpected Challenges in Treating Multidrug-Resistant Gram-Negative Bacteria: Resistance to Ceftazidime-Avibactam in Archived Isolates of Pseudomonas aeruginosa Antimicrobial Agents and Chemotherapy. ,vol. 59, pp. 1020- 1029 ,(2015) , 10.1128/AAC.04238-14
Julian G. Hurdle, Alex J. O'Neill, Ian Chopra, Richard E. Lee, Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections Nature Reviews Microbiology. ,vol. 9, pp. 62- 75 ,(2011) , 10.1038/NRMICRO2474