About us

Lawarence press is an information solution company’s endeavour to bring information among research professionals of the health, science and technology sectors.
We publish contents with the mission to provide information which is universally accessible. We provide easily accessible and elegant online publishing solutions.
Our mission is to empower research work providing web-based digital publishing platform solutions of an international standard. .
Our company vision is to provide the highest standard in an online publishing platform.
We value innovation, originality & quality.

Bifidobacterium Longum as an Orally Administered Carrier of LL-37 to Treat Bacterial Diarrhea

Qing Guo, Shiyu Li, Yajie Xie, Zhenrui Xu, Mengge Liu, Qian Zhang, Hanxiao Sun

Abstract


LL-37 is the only antibacterial peptide of the cathelicidin family found in the human body. It has antimicrobial activity and is able to neutralize endotoxins, with no obvious toxic effects on probiotics. In the present study, we engineered Bifidobacterium longum (B. longum) as an experimentally constructed delivery system of LL-37 to treat bacterial diarrhea. The results showed that the engineered B. longum successfully secreted LL-37, at a level of 57 ± 6.8 ?g/ml after fermentation for 42 h. The supernatant containing recombinant LL-37 significantly inhibited the growth of Escherichia coli (E. coli ) and Staphylococcus aureus (S. aureus), and markedly decreased TNF-? levels in LPS-induced RAW264.7 cells. This modified B. longum was orally administered after bacterial diarrhea was induced with E. coli, and resulted in significant reduction of the proinflammatory cytokine TNF-?. The anti-inflammatory cytokine IL-10 and mucosal repair factor TGF-? were remarkably increased, and the intestinal bacteria Lactobacillus and Bifidobacterium, as well as E. coli, were well-regulated. Histological observations showed colonic protection with dose-modified B. longum. The results demonstrated effective resistance to bacterial diarrhea with LL-37–secreting B. longum.

Keywords


Bifidobacterium longum, LL-37, bacterial diarrhea, endotoxin, antibacterial activity, oral administration

Full Text:

References


Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem. 1996;238:325–332.

Henzler-Wildman KA, Martinez GV, Brown MF, Ramamoorthy A. Perturbation of the hydrophobic core of lipid bilayers by the human antimicrobial peptide LL-37. Biochemistry. 2004; 43:8459–8469.

Bandurska K, Berdowska A, Barczy?ska-Felusiak R, Krupa P. Unique features of human cathelicidin LL-37. Biofactors. 2015; 41:289–300.

Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI. Activities of LL-37, a Cathelin-Associated Antimicrobial Peptide of Human Neutrophils. Antimicrobial Agents & Chemotherapy. 1998;42:2206–2214.

Joly S, Maze C, McCray PB, Guthmiller JM. Human beta-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol. 2004;42:1024–1029.

Howell MD, Jones JF, Kisich KO, Streib JE, Gallo RL, Leung DYM. Selective Killing of Vaccinia Virus by LL-37: Implications for Eczema Vaccinatum. J Immunol. 2004;172:1763–1767.

Wang G, Watson KM, Buckheit RW. Anti-human immunodeficiency virus type 1 activities of antimicrobial peptides derived from human and bovine cathelicidins. Antimicrob Agents Chemother. 2008;52:3438–3440.

Quiñones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS. 2003;17:F39–F48.

Murakami M, Lopez-Garcia B, Braff M, Dorschner RA, Gallo RL. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol. 2004;172:3070–3077.

Hase K, Murakami M, Iimura M, Cole SP, Horibe Y, Ohtake T, et al. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori.

Gastroenterology. 2003; 125:1613–1625.

Iacob SA, Iacob DG. Antibacterial Function of the Human Cathelicidin-18 Peptide (LL-37) between Theory and Practice. Protein & Peptide Lett. 2014;21:1247–1256.

Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun. 1995;63:1291.

Kuroda K, Okumura K, Isogai H, Isogai E. The human cathelicidin antimicrobial peptide LL-37 and mimics are potential anticancer drugs. Front Oncol. 2015;5:144.

Quigley EM. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies. Gastroenterol Clin North Am. 2011;40:207–222.

Sanders ME, Guarner F, Guerrant R, Holt PR, Quigley EM, Sartor RB, et al. An update on the use and investigation of probiotics in health and disease. Gut. 2013;62:787–796.

Li X, Fu GF, Fan YR, Liu WH, Liu XJ, Wang JJ, et al. Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: selective inhibitor of angiogenesis and hypoxic tumor growth. Cancer Gene Ther. 2003;10:105–111.

Long RT, Zeng WS, Chen LY, Guo J, Lin YZ, Huang QS, et al. Bifidobacterium as an oral delivery carrier of oxyntomodulin for obesity therapy: inhibitory effects on food intake and body weight in overweight mice. Int J Obes (Lond). 2010;34:712–719.

Wei P, Yang Y, Liu Z, Huang J, Gong Y, Sun H. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis. Drug Delivery. 2015;23:1.

Yu Z, Huang Z, Sao C, Huang Y, Zhang F, Yang J, et al. Bifidobacterium as an oral delivery carrier of interleukin-12 for the treatment of Coxsackie virus B3-induced myocarditis in the Balb/c mice. Int Immunopharmacol. 2012;12:125–130.

Qu M, Deng Y, Zhang X, Liu G, Huang Y, Lin C, et al. Etiology of acute diarrhea due to enteropathogenic bacteria in Beijing, China. J Infect. 2012;65:214–222.

Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2004;2:CD003048.

Gómez-Duarte OG, Bai J, Newell E. Detection of Escherichia coli, Salmonella spp., Shigella spp., Yersinia enterocolitica, Vibrio cholerae, and Campylobacter spp. enteropathogens by 3-reaction multiplex polymerase chain reaction. 2008;63:1–9.

Wang J, Cheng Y, Wu R, jiang D, Bai B, Tan D, et al. Antibacterial activity of Juglone against Staphylococcus aureus: from apparent to proteomic. Int J Mol Sci. 2016;17:965.

Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2:123–140.

Steffen R, Castelli F, Dieter Nothdurft H, Rombo L, Jane Zuckerman N. Vaccination against enterotoxigenic Escherichia coli, a cause of travelers’ diarrhea. J Travel Med. 2005;12:102–107.

Overbye KM, Barrett JF. Antibiotics: where did we go wrong? Drug Discov Today. 2005;10:45–52.

Takeuchi A, Matsumura H, Kano Y. Cloning and Expression in Escherichia coli of a Gene, hup, Encoding the Histone-like Protein HU of Bifidobacterium longum. Biosci Biotechnol Biochem. 2002;66:598.

Seo JM, Kim JY, Ji GE. Heterologous gene expression and secretion in Bifidobacterium longum. Dairy Sci Technol. 85: 1–8.

Reyes Escogido ML, De León Rodríguez A, Barba de la Rosa AP. A novel binary expression vector for production of human IL-10 in Escherichia coli and Bifidobacterium longum. Biotechnol Lett. 2007;29:1249–1253.

Matteuzzi D, Brigidi P, Rossi M, Di D. Characterization and molecular cloning of Bifidobacterium longum cryptic plasmid pMB1. Lett Appl Microbiol. 1990;11:220–223.

Rossi M, Brigidi P, Matteuzzi D. An efficient transformation system for Bifidobacterium spp. Lett Appl Microbiol. 1997;24:33–36.

Sambrook J, Russell DW. 2006. The condensed protocols from molecular cloning: A laboratory manual, pp. Ed. Cold Spring Harbor Laboratory Press.

Moubareck C, Gavini F, Vaugien L, Butel MJ, Doucet-Populaire F. Antimicrobial susceptibility of bifidobacteria. J Antimicrob Chemother. 2005;55:38–44.

Golec M. 2007. Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide. Ann Agric Environ Med. 2007;14:1-4.

Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Silvestri C, et al. 2006. LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. Antimicrob Agents Chemother. 2006;50:1672–1679.

Overhage J, Campisano A, Bains M, Torfs EC, Rehm BH, Hancock RE. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76:4176–4182.

Kim SJ, Quan R, Lee SJ, Lee HK, Choi JK. Antibacterial activity of recombinant hCAP18/LL37 protein secreted from Pichia pastoris. J Microbiol. 2009;47:358.

Krahulec J, Hyrsová M, Pepeliaev S, Jílková J, Cerný Z, Machálková J. High level expression and purification of antimicrobial human cathelicidin LL-37 in Escherichia coli. Appl Microbiol Biotechnol. 2010;88:167–175.

Gillor O, Etzion A, Riley MA. The dual role of bacteriocins as antiand probiotics. Appl Microbiol Biotechnol. 2008;81:591–606.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 Journal of Pharmaceutical and Biomedical Sciences

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.