Transcriptional and Translational Inhibitors Block SOS Response and Shiga Toxin Expression in Enterohemorrhagic Escherichia coli

Berger, Michael; Aijaz, Iqbal; Berger, Petya; Dobrindt, Ulrich; Koudelka, Gerald B.

doi:10.1038/s41598-019-55332-2

Cited by 21 publications

(22 citation statements)

References 28 publications

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“…We found that the human STEC isolates in this study comprised a high percentage of strains that were susceptible to β-lactams, trimethoprim, and quinolones drugs. It has been reported that when STECs were exposed to inhibitory or sub-inhibitory concentrations of these antibiotics, the SOS reaction would occur [ 14 ]. Hence, it is not recommended to use these antibiotics to treat patients with STEC infections.…”

Section: Discussionmentioning

confidence: 99%

“…The use of antimicrobials to treat STEC infections remains highly controversial and challenging, because some antimicrobial agents can induce Stx production, thus promoting the development of HUS [ 12 , 13 ]. However, other studies have suggested that certain antimicrobials, such as rifaximine, tetracycline, azithromycin, gentamicin, or ampicillin, can block the SOS response (DNA damage response pathway) and Stx production, thus preventing the development of HUS, especially if administered during the early course of the disease [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals

Pan

Bai

et al. 2021

Antibiotics

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Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause zoonotic diseases. To investigate the antimicrobial resistance of STEC in China, non-O157 STEC isolates, recovered from domestic animals and humans from 12 provinces, were analyzed using antimicrobial susceptibility testing and whole genome characterization. Out of the 298 isolates tested, 115 strains showed resistance to at least one antimicrobial and 85 strains showed multidrug resistance. The highest resistance rate was to tetracycline (32.6%), followed by nalidixic acid (25.2%) and chloramphenicol and azithromycin (both 18.8%). However, imipenem and meropenem were effective against all isolates. Antimicrobial resistance patterns varied among strains from different sources. Strains from pig, sheep, humans, and cattle showed resistance rates of 100.0%, 46.9%, 30.3%, and 6.3% to one or more antimicrobials, respectively. Forty-three genes related to 11 antimicrobial classes were identified among these strains. The colistin-resistance gene mcr was only carried by strains from pigs. A new fosfomycin-resistant gene, fosA7, was detected in strains from humans, cattle, and sheep. Whole genome phylogenetic analysis showed that strains from the four sources were genetically diverse and scattered throughout the phylogenetic tree; however, some strains from the same source had a tendency to cluster closely. These results provide a reference to monitor the emergence and spread of multidrug resistant STEC strains among animals and humans. Furthermore, with a better understanding of antimicrobial genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals

Pan

Bai

et al. 2021

Antibiotics

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“…Moreover, previous research has also shown that the bacteriophage-encoded genes stx 1 and stx 2 are upregulated by DNA-damage induced activation of the SOS-response (78,79), while zinc excess has been shown to mute the SOS-response via inhibition of recA (80). In addition, zinc is also known to inhibit expression of further VAGs (81), including those promoting adherence to the gut epithelium (i.e., esp genes) (82).…”

Section: Discussionmentioning

confidence: 99%

High-Zinc Supplementation of Weaned Piglets Affects Frequencies of Virulence and Bacteriocin Associated Genes Among Intestinal Escherichia coli Populations

et al. 2020

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To prevent economic losses due to post-weaning diarrhea (PWD) in industrial pig production, zinc (Zn) feed additives have been widely used, especially since awareness has risen that the regular application of antibiotics promotes buildup of antimicrobial resistance in both commensal and pathogenic bacteria. In a previous study on 179 Escherichia coli collected from piglets sacrificed at the end of a Zn feeding trial, including isolates obtained from animals of a high-zinc fed group (HZG) and a corresponding control group (CG), we found that the isolate collection exhibited three different levels of tolerance toward zinc, i.e., the minimal inhibitory concentration (MIC) detected was 128, followed by 256 and 512 μg/ml ZnCl2. We further provided evidence that enhanced zinc tolerance in porcine intestinal E. coli populations is clearly linked to excessive zinc feeding. Here we provide insights about the genomic make-up and phylogenetic background of these 179 E. coli genomes. Bayesian analysis of the population structure (BAPS) revealed a lack of association between the actual zinc tolerance level and a particular phylogenetic E. coli cluster or even branch for both, isolates belonging to the HZG and CG. In addition, detection rates for genes and operons associated with virulence (VAG) and bacteriocins (BAG) were lower in isolates originating from the HZG (41 vs. 65% and 22 vs. 35%, p < 0.001 and p = 0.002, resp.). Strikingly, E. coli harboring genes defining distinct pathotypes associated with intestinal disease, i.e., enterotoxigenic, enteropathogenic, and Shiga toxin-producing E. coli (ETEC, EPEC, and STEC) constituted 1% of the isolates belonging to the HZG but 14% of those from the CG. Notably, these pathotypes were positively associated with enhanced zinc tolerance (512 μg/ml ZnCl2 MIC, p < 0.001). Taken together, zinc excess seems to influence carriage rates of VAGs and BAGs in porcine intestinal E. coli populations, and high-zinc feeding is negatively correlated with enteral pathotype occurrences, which might explain earlier observations concerning the relative increase of Enterobacterales considering the overall intestinal microbiota of piglets during zinc feeding trials while PWD rates have decreased.

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“…Furthermore, the effects of antibiotics on stx expression vary greatly and are dependent on the antibiotic class, the antibiotic concentration, the respective STEC strain, as well as the Stx subtype (Walterspiel et al, 1992;Grif et al, 1998;Kimmitt et al, 2000;Ochoa et al, 2007;Pedersen et al, 2008;Zhang et al, 2009;McGannon et al, 2010;Bielaszewska et al, 2012;Nassar et al, 2013). While the results obtained from some antibiotic classes, such as β-lactams, are conflicting (Yoh et al, 1997(Yoh et al, , 1999Grif et al, 1998;Yoshimura et al, 1999;McGannon et al, 2010;Muhlen et al, 2020), ansamycins and chloramphenicol consistently yielded promising results in in vitro studies (Kimmitt et al, 2000;Ochoa et al, 2007;McGannon et al, 2010;Kakoullis et al, 2019;Muhlen et al, 2020) while fluoroquinolones were regularly associated with toxin induction (Zhang et al, 2000;Hiramatsu et al, 2003;Bielaszewska et al, 2012;Berger et al, 2019;Muhlen et al, 2020).…”

Section: Antibioticsmentioning

confidence: 99%

“…As studies using antibiotics that inhibit transcription or translation, such as rifamycins, have regularly been shown to inhibit Stx production in vitro and in vivo (Rahal et al, 2011a,b;Corogeanu et al, 2012;Fadlallah et al, 2015;Berger et al, 2019;Muhlen et al, 2020) even after pre-treatment with fluoroquinolone ciprofloxacin (Berger et al, 2019), this opens up the possibility of a potential treatment regimen for STEC infection using antibiotics combination therapy consisting of a transcriptional inhibitor supplied in advance of or simultaneously with an antibiotic such as ciprofloxacin, which efficiently clears the bacterial infection.…”

Section: Antibioticsmentioning

confidence: 99%

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

Mühlen

Dersch

2020

Front. Cell. Infect. Microbiol.

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Infections with Shiga toxin-producing Escherichia coli (STEC) cause outbreaks of severe diarrheal disease in children and the elderly around the world. The severe complications associated with toxin production and release range from bloody diarrhea and hemorrhagic colitis to hemolytic-uremic syndrome, kidney failure, and neurological issues. As the use of antibiotics for treatment of the infection has long been controversial due to reports that antibiotics may increase the production of Shiga toxin, the recommended therapy today is mainly supportive. In recent years, a variety of alternative treatment approaches such as monoclonal antibodies or antisera directed against Shiga toxin, toxin receptor analogs, and several vaccination strategies have been developed and evaluated in vitro and in animal models. A few strategies have progressed to the clinical trial phase. Here, we review the current understanding of and the progress made in the development of treatment options against STEC infections and discuss their potential.

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Transcriptional and Translational Inhibitors Block SOS Response and Shiga Toxin Expression in Enterohemorrhagic Escherichia coli

Cited by 21 publications

References 28 publications

Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals

Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals

High-Zinc Supplementation of Weaned Piglets Affects Frequencies of Virulence and Bacteriocin Associated Genes Among Intestinal Escherichia coli Populations

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

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