There is an urgent need to develop new antibiotics against multidrug-resistant bacteria. Many antimicrobial peptides (AMPs) are active against such bacteria and often act by destabilizing membranes, a mechanism that can also be used to permeabilize bacteria to other antibiotics, resulting in synergistic effects. We recently showed that G3KL, an AMP with a multibranched dendritic topology of the peptide chain, permeabilizes the inner and outer membranes of Gram-negative bacteria including multidrug-resistant strains, leading to efficient bacterial killing. Here, we show that permeabilization of the outer and inner membranes of Pseudomonas aeruginosa by G3KL, initially detected using the DNA-binding fluorogenic dye propidium iodide (PI), also leads to a synergistic effect between G3KL and PI in this bacterium. We also identify a synergistic effect between G3KL and six different antibiotics against the Gram-negative Klebsiella pneumoniae, against which G3KL is inactive.
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Abdel-Sayed P, 2016, SCI REP-UK, V6, DOI [10.1038/srep22020, 10.1038/srep23872]
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D B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USAD B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USA
Amso, Zaid
;
Hayouka, Zvi
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Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, IsraelD B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USA
机构:
Chem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Abgentis, Birmingham, W Midlands, England
Persica Pharmaceut, Canterbury, Kent, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Czaplewski, Lloyd
;
Bax, Richard
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Transcrip Partners Reading, Reading, Berks, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Bax, Richard
;
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Clokie, Martha
;
Dawson, Mike
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Novacta Biosyst, Welwyn Garden City, Herts, England
Cantab Antiinfect, Welwyn Garden City, Herts, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Dawson, Mike
;
Fairhead, Heather
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Phico Therapeut, Cambridge, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Fairhead, Heather
;
Fischetti, Vincent A.
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Rockefeller Univ, Lab Bacterial Pathogenesis & Immunol, 1230 York Ave, New York, NY 10021 USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Fischetti, Vincent A.
;
Foster, Simon
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Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England
Absynth Biol, Liverpool, Merseyside, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Foster, Simon
;
Gilmore, Brendan F.
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Queens Univ, Sch Pharm, Belfast, Antrim, North IrelandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Gilmore, Brendan F.
;
Hancock, Robert E. W.
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Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, CanadaChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Hancock, Robert E. W.
;
Harper, David
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Evolut Biotechnol, Ampthill, Beds, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Harper, David
;
Henderson, Ian R.
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Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Henderson, Ian R.
;
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Hilpert, Kai
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Jones, Brian V.
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Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England
Queen Victoria Hosp NHS Fdn Trust, E Grinstead, W Sussex, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Jones, Brian V.
;
Kadioglu, Aras
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Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Kadioglu, Aras
;
Knowles, David
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Absynth Biol, Liverpool, Merseyside, England
Procarta Biosyst, Norwich, Norfolk, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Knowles, David
;
Olafsdottir, Sigridur
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Iceland Med Agcy, Reykjavik, IcelandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Olafsdottir, Sigridur
;
Payne, David
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GlaxoSmithKline, Collegeville, PA USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Payne, David
;
Projan, Steve
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h-index: 0
机构:
MedImmune, Gaithersburg, MD USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Projan, Steve
;
Shaunak, Sunil
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Univ London Imperial Coll Sci Technol & Med, Dept Med, London, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Shaunak, Sunil
;
Silverman, Jared
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Kaleido Biosci, Cambridge, MA USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Silverman, Jared
;
Thomas, Christopher M.
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Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, England
Plasgene, Birmingham, W Midlands, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Thomas, Christopher M.
;
Trust, Trevor J.
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Pan Prov Vaccine Enterprise, Saskatoon, SK, CanadaChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Trust, Trevor J.
;
Warn, Peter
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Evotec, Manchester, Lancs, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Warn, Peter
;
Rex, John H.
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h-index: 0
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AstraZeneca, Boston, MA USA
F2G, Manchester, Lancs, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
机构:
Walter & Eliza Hall Inst Med Res, Ctr Dynam Imaging, Parkville, Vic 3052, AustraliaMonash Univ, Monash Inst Pharmaceut Sci, Melbourne, Vic 3800, Australia
机构:
D B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USAD B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USA
Amso, Zaid
;
Hayouka, Zvi
论文数: 0引用数: 0
h-index: 0
机构:
Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, IsraelD B A Calibr, Scripps Res Inst, La Jolla, CA 92037 USA
机构:
Chem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Abgentis, Birmingham, W Midlands, England
Persica Pharmaceut, Canterbury, Kent, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Czaplewski, Lloyd
;
Bax, Richard
论文数: 0引用数: 0
h-index: 0
机构:
Transcrip Partners Reading, Reading, Berks, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Bax, Richard
;
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Clokie, Martha
;
Dawson, Mike
论文数: 0引用数: 0
h-index: 0
机构:
Novacta Biosyst, Welwyn Garden City, Herts, England
Cantab Antiinfect, Welwyn Garden City, Herts, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Dawson, Mike
;
Fairhead, Heather
论文数: 0引用数: 0
h-index: 0
机构:
Phico Therapeut, Cambridge, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Fairhead, Heather
;
Fischetti, Vincent A.
论文数: 0引用数: 0
h-index: 0
机构:
Rockefeller Univ, Lab Bacterial Pathogenesis & Immunol, 1230 York Ave, New York, NY 10021 USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Fischetti, Vincent A.
;
Foster, Simon
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England
Absynth Biol, Liverpool, Merseyside, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Foster, Simon
;
Gilmore, Brendan F.
论文数: 0引用数: 0
h-index: 0
机构:
Queens Univ, Sch Pharm, Belfast, Antrim, North IrelandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Gilmore, Brendan F.
;
Hancock, Robert E. W.
论文数: 0引用数: 0
h-index: 0
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Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, CanadaChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Hancock, Robert E. W.
;
Harper, David
论文数: 0引用数: 0
h-index: 0
机构:
Evolut Biotechnol, Ampthill, Beds, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Harper, David
;
Henderson, Ian R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Henderson, Ian R.
;
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Hilpert, Kai
;
Jones, Brian V.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England
Queen Victoria Hosp NHS Fdn Trust, E Grinstead, W Sussex, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Jones, Brian V.
;
Kadioglu, Aras
论文数: 0引用数: 0
h-index: 0
机构:
Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Kadioglu, Aras
;
Knowles, David
论文数: 0引用数: 0
h-index: 0
机构:
Absynth Biol, Liverpool, Merseyside, England
Procarta Biosyst, Norwich, Norfolk, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Knowles, David
;
Olafsdottir, Sigridur
论文数: 0引用数: 0
h-index: 0
机构:
Iceland Med Agcy, Reykjavik, IcelandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Olafsdottir, Sigridur
;
Payne, David
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline, Collegeville, PA USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Payne, David
;
Projan, Steve
论文数: 0引用数: 0
h-index: 0
机构:
MedImmune, Gaithersburg, MD USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Projan, Steve
;
Shaunak, Sunil
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Med, London, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Shaunak, Sunil
;
Silverman, Jared
论文数: 0引用数: 0
h-index: 0
机构:
Kaleido Biosci, Cambridge, MA USAChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Silverman, Jared
;
Thomas, Christopher M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Inst Microbiol & Infect, Birmingham, W Midlands, England
Plasgene, Birmingham, W Midlands, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Thomas, Christopher M.
;
Trust, Trevor J.
论文数: 0引用数: 0
h-index: 0
机构:
Pan Prov Vaccine Enterprise, Saskatoon, SK, CanadaChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Trust, Trevor J.
;
Warn, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Evotec, Manchester, Lancs, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
Warn, Peter
;
Rex, John H.
论文数: 0引用数: 0
h-index: 0
机构:
AstraZeneca, Boston, MA USA
F2G, Manchester, Lancs, EnglandChem Biol Ventures, 123 Alexander Close, Abingdon OX14 1XD, Oxon, England
机构:
Walter & Eliza Hall Inst Med Res, Ctr Dynam Imaging, Parkville, Vic 3052, AustraliaMonash Univ, Monash Inst Pharmaceut Sci, Melbourne, Vic 3800, Australia