RESUMEN
Shiga toxin (Stx)-producing Escherichia coli (STEC) is associated with hemolytic uremic syndrome (HUS). High inflammatory cytokine [interleukin (IL)-6 and IL-8] levels and low anti-inflammatory cytokine (IL-10) levels are indicators of a high risk for developing HUS in STEC-infected children. In this study, we investigated inhibitory action of telithromycin, a ketolide, against STEC and against Stx and lipopolysaccharide (LPS). Telithromycin inhibited in vitro STEC growth without inducing Stx phage, in marked contrast to norfloxacin. Stx markedly induced inflammatory (but not anti-inflammatory) cytokine production in human peripheral blood monocytes, while LPS induced both inflammatory and anti-inflammatory cytokine production. Telithromycin selectively inhibited the IL-6 and IL-8 production from Stx-stimulated (but not LPS-stimulated) monocytes. The drug did not significantly inhibit IL-10 production. Our data suggest that Stx plays a crucial role in the stimulation of inflammatory cytokines and such inflammatory response is inhibited by telithromycin, an anti-bacterial agent.
Asunto(s)
Endotoxinas/antagonistas & inhibidores , Cetólidos , Macrólidos/farmacología , Toxina Shiga/antagonistas & inhibidores , Adulto , Citocinas/biosíntesis , Humanos , Técnicas In Vitro , Lipopolisacáridos/farmacología , Monocitos/efectos de los fármacos , Monocitos/metabolismoRESUMEN
Shiga toxin (Stx)-producing Escherichia coli (STEC), an important cause of hemolytic uremic syndrome, was completely killed by (60)Co irradiation at 1 x l0(3) gray (1 kGy) or higher. However, a low dose of irradiation (0.1-0.3 kGy) markedly induced Stx phage from STEC. Stx production was observed in parallel to the phage induction. Inactivation of Stx phage required a higher irradiation dose than that for bacterial killing. Regarding Stx, cytotoxicity was susceptible to irradiation, but cytokine induction activity was more resistant than Stx phage. The findings suggest that (1). although (60)Co irradiation is an effective means to kill the bacteria, it does induce Stx phage at a lower irradiation dose, with a risk of Stx phage transfer and emergence of new Stx-producing strains, and (2). irradiation differentially inactivates some activities of Stx.
Asunto(s)
Bacteriófagos/efectos de la radiación , Escherichia coli/efectos de la radiación , Escherichia coli/virología , Contaminación de Alimentos/prevención & control , Toxina Shiga/biosíntesis , Animales , Bacteriófagos/crecimiento & desarrollo , Bacteriófagos/metabolismo , Bovinos , Radioisótopos de Cobalto , ADN Bacteriano/efectos de la radiación , Escherichia coli/metabolismo , Humanos , Plásmidos/efectos de la radiaciónAsunto(s)
Cólera/microbiología , Vibrio cholerae , Proteínas Bacterianas/genética , Bacteriófagos , Cólera/diagnóstico , Cólera/epidemiología , Cólera/terapia , Toxina del Cólera/química , Diagnóstico Diferencial , Brotes de Enfermedades , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos/genética , Humanos , Lipopolisacáridos/química , Técnicas de Diagnóstico Molecular , Pronóstico , Serotipificación , Vibrio cholerae/clasificación , Vibrio cholerae/genética , Vibrio cholerae/patogenicidad , Virulencia/genética , Factores de Virulencia/genéticaAsunto(s)
Vibriosis , Vibrio parahaemolyticus , Vibrio vulnificus , Animales , Bacteriemia/microbiología , Toxinas Bacterianas , Traslocación Bacteriana , Cromosomas Bacterianos/genética , Diagnóstico Diferencial , Proteínas Hemolisinas/genética , Humanos , Pronóstico , Serotipificación , Vibriosis/diagnóstico , Vibriosis/epidemiología , Vibriosis/microbiología , Vibriosis/terapia , Vibrio parahaemolyticus/clasificación , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/patogenicidad , Vibrio vulnificus/clasificación , Vibrio vulnificus/genética , Factores de Virulencia , Infección de Heridas/microbiologíaRESUMEN
Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-alpha, IL-1beta, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.