Treatment with rokitamycin suppresses the lethality in a murine model of Escherichia coli O157:H7 infection

Hiramatsu, Kazufumi; Murakami, Junko; Kishi, Kenji; Hirata, Norio; Yamasaki, Takahiro; Kadota, Jun‐ichi; Shibata, Tetsuo; Nasu, Masaru

doi:10.1016/s0924-8579(03)00007-4

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…Recently, it was reported that rokitamycin may be considered bactericidal against Borrelia burgdorferi and Escherichia coli O157:H7 [30,31]. In the case of Acanthamoeba castellanii, the effects of rokitamycin when used at the minimal dose were amoebistatic, but they were amoebicidal as well as cysticidal at higher doses [8].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

Kim

Lee

Sohn

et al. 2008

International Journal of Antimicrobial Agents

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Section: Discussionmentioning

confidence: 99%

Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

Kim

Lee

Sohn

et al. 2008

International Journal of Antimicrobial Agents

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“…Some animal studies used to mimic STEC-or Stx-mediated disease in response to antibiotic treatment confirmed previous in vitro results, while others were contradicting the in vitro data (Zhang et al, 2000(Zhang et al, , 2009Rahal et al, 2011a;Zangari et al, 2014;Kakoullis et al, 2019). Interestingly, the in vivo studies confirmed a detrimental effect of fluoroquinolone antibiotics (Zhang et al, 2000;Hiramatsu et al, 2003;Muhlen et al, 2020) and a reduction of disease pathology when animals were treated with rifamycin antibiotics (Rahal et al, 2011a,b;Muhlen et al, 2020).…”

Section: Antibioticsmentioning

confidence: 64%

“…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%

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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“…Our data are in agreement with data from previous research demonstrating the therapeutic benefits of macrolide treatment on EHEC infections. Two independent studies have shown that azithromycin ( 53 ) and rokitamycin ( 54 ) treatment reduces lethality and Stx-related systemic alterations in different animal models of EHEC infection. However, these studies link the clinical benefit of this therapy only to a reduction in the levels of Stx production.…”

Section: Discussionmentioning

confidence: 99%

Type III Secretion-Dependent Sensitivity of Escherichia coli O157 to Specific Ketolides

Fernández-Brando

Yamaguchi

Tahoun

et al. 2016

Antimicrob Agents Chemother

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A subset of Gram-negative bacterial pathogens uses a type III secretion system (T3SS) to open up a conduit into eukaryotic cells in order to inject effector proteins. These modulate pathways to enhance bacterial colonization. In this study, we screened established bioactive compounds for any that could repress T3SS expression in enterohemorrhagic Escherichia coli (EHEC) O157. The ketolides telithromycin and, subsequently, solithromycin both demonstrated repressive effects on expression of the bacterial T3SS at sub-MICs, leading to significant reductions in bacterial binding and actin-rich pedestal formation on epithelial cells. Preincubation of epithelial cells with solithromycin resulted in significantly less attachment of E. coli O157. Moreover, bacteria expressing the T3SS were more susceptible to solithromycin, and there was significant preferential killing of E. coli O157 bacteria when they were added to epithelial cells that had been preexposed to the ketolide. This killing was dependent on expression of the T3SS. Taken together, this research indicates that the ketolide that has accumulated in epithelial cells may traffic back into the bacteria via the T3SS. Considering that neither ketolide induces the SOS response, nontoxic members of this class of antibiotics, such as solithromycin, should be considered for future testing and trials evaluating their use for treatment of EHEC infections. These antibiotics may also have broader significance for treating infections caused by other pathogenic bacteria, including intracellular bacteria, that express a T3SS.

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Treatment with rokitamycin suppresses the lethality in a murine model of Escherichia coli O157:H7 infection

Cited by 9 publications

References 22 publications

Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

Therapeutic effect of rokitamycin in vitro and on experimental meningoencephalitis due to Naegleria fowleri

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

Type III Secretion-Dependent Sensitivity of Escherichia coli O157 to Specific Ketolides

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