Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7

Abstract Infection with Shiga toxin-producing Escherichia coli (STEC) results in hemorrhagic colitis and can lead to life-threatening sequelae including hemolytic uremic syndrome (HUS). Conventional treatment is intravenous fluid volume expansion. Antibiotic treatment is contraindicated, due in part...

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Autores principales:	Juan Puño-Sarmiento, Erin M. Anderson, Amber J. Park, Cezar M. Khursigara, Debora E. Barnett Foster
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0edb1c5c948142bd894bb0fce1d656c6
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spelling	oai:doaj.org-article:0edb1c5c948142bd894bb0fce1d656c62021-12-02T17:45:21ZPotentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H710.1038/s41598-020-66571-z2045-2322https://doaj.org/article/0edb1c5c948142bd894bb0fce1d656c62020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66571-zhttps://doaj.org/toc/2045-2322Abstract Infection with Shiga toxin-producing Escherichia coli (STEC) results in hemorrhagic colitis and can lead to life-threatening sequelae including hemolytic uremic syndrome (HUS). Conventional treatment is intravenous fluid volume expansion. Antibiotic treatment is contraindicated, due in part to the elevated risk of HUS related to increased Shiga toxin (Stx) release associated with some antibiotics. Given the lack of effective strategies and the increasing number of STEC outbreaks, new treatment approaches are critically needed. In this study, we used an antimicrobial peptide wrwycr, previously shown to enhance STEC killing without increasing Stx production, in combination with antibiotic treatments. Checkerboard and time-kill assays were used to assess peptide wrwycr-antibiotic combinations for synergistic STEC killing. Cytotoxicity and real-time PCR were used to evaluate Stx production and stx expression, respectively, associated with these combinations. The synergistic combinations that showed rapid killing, no growth recovery and minimal Stx production were peptide wrwycr-kanamycin/gentamicin. Transmission electron microscopy revealed striking differences in bacterial cell morphology associated with various treatments. This study provides proof of principle for the design of an antibiotic-peptide wrwycr combination effective in killing STEC without enhancing release of Shiga toxins. It also offers a strategy for the repurposing of antibiotics for treatment of STEC infection.Juan Puño-SarmientoErin M. AndersonAmber J. ParkCezar M. KhursigaraDebora E. Barnett FosterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juan Puño-Sarmiento Erin M. Anderson Amber J. Park Cezar M. Khursigara Debora E. Barnett Foster Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
description	Abstract Infection with Shiga toxin-producing Escherichia coli (STEC) results in hemorrhagic colitis and can lead to life-threatening sequelae including hemolytic uremic syndrome (HUS). Conventional treatment is intravenous fluid volume expansion. Antibiotic treatment is contraindicated, due in part to the elevated risk of HUS related to increased Shiga toxin (Stx) release associated with some antibiotics. Given the lack of effective strategies and the increasing number of STEC outbreaks, new treatment approaches are critically needed. In this study, we used an antimicrobial peptide wrwycr, previously shown to enhance STEC killing without increasing Stx production, in combination with antibiotic treatments. Checkerboard and time-kill assays were used to assess peptide wrwycr-antibiotic combinations for synergistic STEC killing. Cytotoxicity and real-time PCR were used to evaluate Stx production and stx expression, respectively, associated with these combinations. The synergistic combinations that showed rapid killing, no growth recovery and minimal Stx production were peptide wrwycr-kanamycin/gentamicin. Transmission electron microscopy revealed striking differences in bacterial cell morphology associated with various treatments. This study provides proof of principle for the design of an antibiotic-peptide wrwycr combination effective in killing STEC without enhancing release of Shiga toxins. It also offers a strategy for the repurposing of antibiotics for treatment of STEC infection.
format	article
author	Juan Puño-Sarmiento Erin M. Anderson Amber J. Park Cezar M. Khursigara Debora E. Barnett Foster
author_facet	Juan Puño-Sarmiento Erin M. Anderson Amber J. Park Cezar M. Khursigara Debora E. Barnett Foster
author_sort	Juan Puño-Sarmiento
title	Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
title_short	Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
title_full	Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
title_fullStr	Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
title_full_unstemmed	Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7
title_sort	potentiation of antibiotics by a novel antimicrobial peptide against shiga toxin producing e. coli o157:h7
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0edb1c5c948142bd894bb0fce1d656c6
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Potentiation of Antibiotics by a Novel Antimicrobial Peptide against Shiga Toxin Producing E. coli O157:H7

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