A novel tetrabranched antimicrobial peptide that neutralizes bacterial lipopolysaccharide and prevents septic shock in vivo

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Alessandro PiniLuisa Bracci

Abstract

We describe the nonnatural antimicrobial peptide KKIRVRLSA (M33) and its capacity to neutralize LPS-induced cytokine release, preventing septic shock in animals infected with bacterial species of clinical interest. M33 showed strong resistance to proteolytic degradation when synthesized in tetrabranched form with 4 peptides linked by a lysine core, making it suitable for use in vivo. HPLC and mass spectrometry demonstrated its stability in serum beyond 24 h. M33 was found to be very selective for gram-negative bacteria. Minimal inhibitory concentration (MIC) ranged from 0.3 to 3 muM for multidrug resistant clinical isolates of several pathogenic species, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. M33 neutralized LPS derived from P. aeruginosa and K. pneumoniae, and prevented TNF-alpha release from LPS-activated macrophages, with an EC(50) of 3.8e-8 M and 2.8e-7 M, respectively, as detected by sandwich ELISA. M33 activity was also tested in sepsis animal models. It averted septic shock symptoms due to Escherichia coli and P. aeruginosa in doses compatible with clinical use (5-25 mg/kg). These properties make tetrabranched M33 peptide a good candidate for the development of a new antibac...Continue Reading

References

Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J P Tam
Jan 1, 1993·Cancer Chemotherapy and Pharmacology·K A Peck-MillerH P Fell
Nov 19, 2002·Antimicrobial Agents and Chemotherapy·Michael R YeamanEric P Brass
Sep 16, 2003·The Journal of Biological Chemistry·Luisa BracciPaolo Neri
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dawn M E BowdishRobert E W Hancock
Jun 28, 2005·Pharmacotherapy·William A Prescott, Cary E Johnson
Jun 28, 2005·Antimicrobial Agents and Chemotherapy·Alessandro PiniLuisa Bracci
Jun 28, 2005·Antimicrobial Agents and Chemotherapy·Lijuan ZhangTimothy J Falla
Jul 16, 2005·Current Eye Research·Y Jerold GordonAlison M McDermott
Dec 13, 2005·American Journal of Respiratory Cell and Molecular Biology·Y Elaine LauDonald J Davidson
Mar 25, 2006·Expert Opinion on Pharmacotherapy·Lijuan Zhang, Timothy J Falla
Apr 28, 2006·Antimicrobial Agents and Chemotherapy·Oscar CirioniGiorgio Scalise
Jun 23, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dirk MotzkusErik Maronde
Aug 8, 2006·Current Opinion in Pharmacology·Alexandra K MarrRobert Ew Hancock
Dec 13, 2006·Nature Biotechnology·Robert E W Hancock, Hans-Georg Sahl
Apr 11, 2007·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Tamra M ArnoldKaren J Messmer
Apr 20, 2007·Chemical Biology & Drug Design·Chiara FalcianiLuisa Bracci
May 9, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Alessandro PiniLuisa Bracci
Aug 19, 2007·Nanomedicine : Nanotechnology, Biology, and Medicine·Greta RossettoGiovanna Pirri
Sep 4, 2007·Molecular Cancer Therapeutics·Chiara FalcianiLuisa Bracci
Sep 20, 2007·The Journal of Antimicrobial Chemotherapy·Alexandre Prehn ZavasckiRoger L Nation
Mar 26, 2008·Critical Care Clinics·Argyris Michalopoulos, Matthew E Falagas
Aug 6, 2008·Protein and Peptide Letters·Alessandro PiniLuisa Bracci
Sep 24, 2008·Antimicrobial Agents and Chemotherapy·Gian Maria RossoliniLaura Pagani
Oct 16, 2008·Current Protein & Peptide Science·Alessandro PiniLuisa Bracci
Dec 17, 2008·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·G M Rossolini, E Mantengoli
Feb 25, 2009·Expert Opinion on Biological Therapy·Chiara FalcianiLuisa Bracci
Apr 30, 2009·Advances in Experimental Medicine and Biology·Monica FabbriniLuisa Bracci
May 16, 2009·Protein and Peptide Letters·Kwong-Fai Wong, John M Luk

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Citations

Mar 4, 2011·Applied Microbiology and Biotechnology·Klaus BrandenburgThomas Gutsmann
Jun 16, 2012·The Journal of Biological Chemistry·Yang BaiKonstantin Pervushin
Mar 7, 2012·Antimicrobial Agents and Chemotherapy·E N LorenzónE M Cilli
Mar 21, 2012·Critical Care : the Official Journal of the Critical Care Forum·Tobias SchuerholzGernot Marx
Jan 11, 2013·Critical Care : the Official Journal of the Critical Care Forum·Tobias SchuerholzGernot Marx
May 21, 2011·Cellular and Molecular Life Sciences : CMLS·Andrea Giuliani, Andrea C Rinaldi
Jun 5, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jlenia BrunettiAlessandro Pini
Oct 6, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Pramod JagtapShalini Gupta
Feb 9, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Simona PolliniChiara Falciani
Mar 8, 2019·FEMS Microbiology Reviews·Tomasz Skirecki, Jean-Marc Cavaillon
Feb 29, 2020·International Journal of Nanomedicine·Chiara FalcianiAlessandro Pini
Oct 21, 2016·The Journal of Biological Chemistry·Jlenia BrunettiAlessandro Pini
Nov 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca CastigliaChiara Falciani
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Leila QuerciniAlessandro Pini
Jul 9, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matthew DraytonSuzana K Straus
Oct 22, 2020·Research : a Science Partner Journal·Zifang ShangWei Huang
May 30, 2019·International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition·Elham Nourmohammadi, Alireza Sadeghi Mahoonak

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