Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice

<p>Abstract</p> <p>Background</p> <p>Treatment of <it>Escherichia coli </it>O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the p...

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Main Authors: Abdelnoor Alexander M, Sabra Ahmad, Kazzi Natalie, Rahal Elias A, Matar Ghassan M
Format: Article
Language:English
Published: BMC 2011-09-01
Series:Annals of Clinical Microbiology and Antimicrobials
Subjects:
Online Access:http://www.ann-clinmicrob.com/content/10/1/34
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author Abdelnoor Alexander M
Sabra Ahmad
Kazzi Natalie
Rahal Elias A
Matar Ghassan M
author_facet Abdelnoor Alexander M
Sabra Ahmad
Kazzi Natalie
Rahal Elias A
Matar Ghassan M
author_sort Abdelnoor Alexander M
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Treatment of <it>Escherichia coli </it>O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy.</p> <p>Methods</p> <p>The utility of decreasing Shiga toxin gene expression in <it>E. coli </it>O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated <it>in vitro </it>using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of <it>E. coli </it>O157:H7-infected BALB/c mice was also monitored.</p> <p>Results</p> <p>Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating <it>E. coli </it>O157:H7 <it>in vitro </it>with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from <it>E. coli </it>O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with <it>E. coli </it>O157:H7 was observed in those treated with the <it>in vivo </it>MIC equivalent dose of rifampicin followed by the <it>in vivo </it>MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.</p> <p>Conclusions</p> <p>The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating <it>E. coli </it>O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing <it>E. coli </it>strains.</p>
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spelling doaj.art-2b45b2b26c484c9d84cb2829702745a92022-12-22T01:38:06ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112011-09-011013410.1186/1476-0711-10-34Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c miceAbdelnoor Alexander MSabra AhmadKazzi NatalieRahal Elias AMatar Ghassan M<p>Abstract</p> <p>Background</p> <p>Treatment of <it>Escherichia coli </it>O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy.</p> <p>Methods</p> <p>The utility of decreasing Shiga toxin gene expression in <it>E. coli </it>O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated <it>in vitro </it>using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of <it>E. coli </it>O157:H7-infected BALB/c mice was also monitored.</p> <p>Results</p> <p>Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating <it>E. coli </it>O157:H7 <it>in vitro </it>with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from <it>E. coli </it>O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with <it>E. coli </it>O157:H7 was observed in those treated with the <it>in vivo </it>MIC equivalent dose of rifampicin followed by the <it>in vivo </it>MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.</p> <p>Conclusions</p> <p>The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating <it>E. coli </it>O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing <it>E. coli </it>strains.</p>http://www.ann-clinmicrob.com/content/10/1/34<it>Escherichia coli </it>O157:H7rifampicingentamicinShiga toxins
spellingShingle Abdelnoor Alexander M
Sabra Ahmad
Kazzi Natalie
Rahal Elias A
Matar Ghassan M
Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
Annals of Clinical Microbiology and Antimicrobials
<it>Escherichia coli </it>O157:H7
rifampicin
gentamicin
Shiga toxins
title Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
title_full Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
title_fullStr Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
title_full_unstemmed Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
title_short Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of <it>Escherichia coli </it>O157:H7-infected BALB/c mice
title_sort decrease in shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of it escherichia coli it o157 h7 infected balb c mice
topic <it>Escherichia coli </it>O157:H7
rifampicin
gentamicin
Shiga toxins
url http://www.ann-clinmicrob.com/content/10/1/34
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