Dataset Information

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 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.

SUBMITTER: Puno-Sarmiento J

PROVIDER: S-EPMC7308376 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Puño-Sarmiento Juan J Anderson Erin M EM Park Amber J AJ Khursigara Cezar M CM Barnett Foster Debora E DE

Scientific reports 20200622 1

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 a ...[more]

PMID: 32572054

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Project description:In this study, four antimicrobial growth promoters, including virginiamycin, josamycin, flavophospholipol, poly 2-propenal 2-propenoic acid and ultraviolet light, were tested for their capacity to induce stx-bacteriophages in 47 Shiga toxin-producing E. coli O157:H7 isolates. Induced bacteriophages were characterized for shiga toxin subtypes and structural genes by PCR, DNA restriction fragment length polymorphisms (RFLP) and morphological features by electron microscopy. Bacteriophages were induced from 72.3% (34/47) of the STEC O157:H7 isolates tested. Bacteriophage induction rates per induction method were as follows: ultraviolet light, 53.2% (25/47); poly 2-propenal 2-propenoic acid, 42.6% (20/47); virginiamycin, 34.0% (16/47); josamycin, 34.0% (16/47); and flavophospholipol, 29.8% (14/47). A total of 98 bacteriophages were isolated, but only 59 were digestible by NdeI, revealing 40 RFLP profiles which could be subdivided in 12 phylogenetic subgroups. Among the 98 bacteriophages, stx2a, stx2c and stx2d were present in 85.7%, 94.9% and 36.7% of bacteriophages, respectively. The Q, P, CIII, N1, N2 and IS1203 genes were found in 96.9%, 82.7%, 69.4%, 40.8%, 60.2% and 73.5% of the samples, respectively. Electron microscopy revealed four main representative morphologies which included three bacteriophages which all had long tails but different head morphologies: long hexagonal head, oval/oblong head and oval/circular head, and one bacteriophage with an icosahedral/hexagonal head with a short thick contractile tail. This study demonstrated that virginiamycin, josamycin, flavophospholipol and poly 2-propenal 2-propenoic acid induce genetically and morphologically diverse free stx-converting bacteriophages from STEC O157:H7. The possibility that these antimicrobial growth promoters may induce bacteriophages in vivo in animals and human hosts is a public health concern. Policies aimed at minimizing or banning the use of antimicrobial growth promoters should be promoted and implemented in countries where these compounds are still in use in animal agriculture.

Dataset Information

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

Publications

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

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