An
            <i>In Vitro</i>
            Combined Antibiotic-Antibody Treatment Eliminates Toxicity from Shiga Toxin-Producing Escherichia coli

Skinner, Craig; Zhang, Guodong; Patfield, Stephanie; He, Xiaohua

doi:10.1128/aac.00763-15

Cited by 14 publications

(9 citation statements)

References 44 publications

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“…β-lactam antimicrobials, especially at sub-inhibitory concentrations, can increase Shiga toxin production and release by O157 bacteria in vitro [ 6 , 7 , 9 , 20 ]. The specific mechanism(s) for these effects have not been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes

et al. 2021

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Treatment of Shiga toxin-producing Escherichia coli O157 (O157) diarrhea with antimicrobials might alter the risk of hemolytic uremic syndrome (HUS). However, full characterization of which antimicrobials might affect risk is lacking, particularly among adults. To inform clinical management, we conducted a case-control study of residents of the FoodNet surveillance areas with O157 diarrhea during a 4-year period to assess antimicrobial class-specific associations with HUS among persons with O157 diarrhea. We collected data from medical records and patient interviews. We measured associations between treatment with agents in specific antimicrobial classes during the first week of diarrhea and development of HUS, adjusting for age and illness severity. We enrolled 1308 patients; 102 (7.8%) developed confirmed HUS. Antimicrobial treatment varied by age: <5 years (12.6%), 5–14 (11.5%), 15–39 (45.4%), ≥40 (53.4%). Persons treated with a β-lactam had higher odds of developing HUS (OR 2.80, CI 1.14–6.89). None of the few persons treated with a macrolide developed HUS, but the protective association was not statistically significant. Exposure to “any antimicrobial” was not associated with increased odds of HUS. Our findings confirm the risk of β-lactams among children with O157 diarrhea and extends it to adults. We observed a high frequency of inappropriate antimicrobial treatment among adults. Our data suggest that antimicrobial classes differ in the magnitude of risk for persons with O157 diarrhea.

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Section: Discussionmentioning

confidence: 99%

Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes

et al. 2021

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“…The use of Stx receptor analogs ( Nishikawa et al, 2002 , 2005 ) and antibodies specific to the toxins has also been reported. A strategy that combined antibiotics and antibody specific for the Stx appeared effective in in vitro experiments ( Skinner et al, 2015 ). The small molecule Retro-2 cycl that functions by inhibiting host retrograde trafficking is effective against infections caused by the EHEC strain O104:H4 in a mouse disease model ( Secher et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Baicalin Protects Mice from Lethal Infection by Enterohemorrhagic Escherichia coli

Liu

et al. 2017

Front. Microbiol.

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Shiga-like toxin-producing Escherichia coli (STEC) O157:H7 poses grave challenges to public health by its ability to cause severe colonic diseases and renal failure in both human and animals. Shiga-like toxins are the major pathogenic factor for some highly virulent E. coli expecially Shiga-like toxin 2. Conventional treatments such as antibiotics can facilitate the release of the toxin thus potentially exacerbate the diseases. Small molecule inhibitors and antibodies capable of neutralizing the toxins are the two major venues for the development of therapeutics against enterohemorrhagic serotype E. coli infection. While promising and potentially effective at clinical settings, these approaches need to overcome obstacles such as the limited routes of administration, responses from the host immune system, which are known to differ greatly among individuals. Our previous studies demonstrate that Baicalin (BAI), a flavonoid compound isolated from Scutellaria baicalensis protects against rStx2-induced cell cytotoxicity and also protects mice from lethal rStx2 challenges by inducing Stx2 to form inactive oligomers. In this manuscript, we present some exciting work showing that baicalin is an effective agent for therapeutic treatment of STEC O157:H7 infection.

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“…Membranes were then washed with TBST three times at room temperature for 3 min with gentle agitation. Primary antibody solution containing antibody to Stx1-1 or Stx2-5 (Skinner et al, 2014, 2015; Wang et al, 2016) at dilutions 1:1000 in TBST with 5% NFDM was added to blots and allowed to incubate overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Three Dimensional Vero Cell-Platform for Rapid and Sensitive Screening of Shiga-Toxin Producing Escherichia coli

Bhunia

2019

Front. Microbiol.

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Shiga-toxin producing Escherichia coli (STEC) is a serious public health concern. Current Vero cell assay, although sensitive, is lengthy and requires 48–72 h to assess STEC presence in a sample. In this study, we investigated if Vero cells in a three-dimensional (3D) platform would provide improved sensitivity for rapid screening of STEC. Vero cells (epithelial kidney cell line) were grown as a monolayer (2D) or in a collagen-matrix (3D) and exposed to Shiga-toxin (Stx) preparation or STEC cells that were pre-exposed to antibiotics (mitomycin C, ciprofloxacin, or polymyxin B) for toxin induction. Lactate dehydrogenase (LDH) release from Vero cells was used as a biomarker for cytotoxicity. Modified tryptic soy broth (mTSB) as enrichment broth containing mitomycin C (2 μg/ml) or ciprofloxacin (100 ng/ml) significantly induced Stx production, which was further confirmed by the dot-immunoblot assay. The 3D Vero platform detected STEC after 6 h post-infection with cytotoxicity values ranging from 33 to 79%, which is considerably faster than the traditional 2D platform, when tested with STEC. The cytotoxicity for non-Stx producing bacteria, Salmonella , Listeria , Citrobacter , Serratia , and Hafnia was found to be below the cytotoxicity cutoff value of 15%. The detection limit for the 3D Vero cell assay was estimated to be 10 7 CFU/ml for bacteria and about 32 ng/ml for Stx in 6 h. STEC-inoculated ground beef samples ( n = 27) resulted in 38–46% cytotoxicity, and the bacterial isolates ( n = 42) from ground beef samples were further confirmed to be stx1 and stx2 positive in a multiplex PCR yielding a very low false-positive result. This 3D cell-based screening assay relies on mammalian cell pathogen interaction that can complement other molecular techniques for the detection of cell-free Stx or STEC cells from food samples for early detection and prevention.

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An In Vitro Combined Antibiotic-Antibody Treatment Eliminates Toxicity from Shiga Toxin-Producing Escherichia coli

Cited by 14 publications

References 44 publications

Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes

Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes

Baicalin Protects Mice from Lethal Infection by Enterohemorrhagic Escherichia coli

Three Dimensional Vero Cell-Platform for Rapid and Sensitive Screening of Shiga-Toxin Producing Escherichia coli

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