Immunization of pregnant cows with Shiga toxin-2 induces high levels of specific colostral antibodies and lactoferrin able to neutralize E. coli O157:H7 pathogenicity

Hua

et al. 2019

Sci Rep

The zoonotic enterohaemorrhagic Escherichia coli (EHEC) O157:H7 can disrupt intestinal epithelial barrier function and in turn leading to serious intestinal and systemic disease. PR39 could effectively inhibit the growth of Gram-negative bacteria, but there is little knowledge of its effects on intestinal barrier function and the microbiota in E . coli -challenged mice. In this study, an intestinal disease caused by EHEC O157:H7 was established, to analyze the effect of PR39 on EHEC O157:H7 induced intestinal epithelial barrier injury and disorder. Interestingly, PR39 attenuated EHEC O157:H7-induced systemic symptoms and significantly decreased mortality and the degree of E . coli shedding in faeces. Furthermore, the infiltration index of macrophages and neutrophils in intestine of the PR39 treatment group were obviously attenuated, along with the level of apoptosis. PR39 treatment group had distinctly improved tight junction associated proteins’ expression after EHEC O157:H7 caused injury. Additionally, the sequencing analysis of cecum microbiota showed that PR39 altered the abnormal increase in Bacteroides caused by EHEC O157:H7 and promoted the growth of probiotics such as Lactobacillus . In conclusion, cathelicidin-derived PR39 could effectively improve EHEC O157:H7-induced epithelial barrier injury, and dysfunction of immune and microbiota homeostasis in the intestinal tract, indicating that PR39 could be an excellent potential drug for zoonotic EHEC O157:H7-related intestinal disease.

Section: Discussionmentioning

confidence: 99%

Cathelicidin- derived PR39 protects enterohemorrhagic Escherichia coli O157:H7 challenged mice by improving epithelial function and balancing the microbiota in the intestine

Hua

et al. 2019

Sci Rep

“…application to calves of Shiga toxoids led to substantial anti-Stx1 as well as anti-Stx2 titres without causing any adverse effects [72]. Vaccination-induced anti-Stx bovine antibodies neutralize the biological activity of the holotoxin in vitro [72] in in vivo [140][141][142] in various models. The poor immunogenicity of Stxs upon natural exposure and the absence of Stx-specific seroconversion seen after experimental STEC infection of calves [29,138], cannot be explained by a damage of B cells by Stxs also.…”

Section: Impact On the Humoral Immune Responsementioning

confidence: 99%

“…Immunization of pregnant cows with Stxs results in colostrums enriched in anti-Stx1 and anti-Stx2 [142,223]. Such colostrums, or preparations thereof, reduce STEC shedding by experimentally infected dogs [140] and mitigate Stx2 absorption from the intestine of mice [141].…”

Section: Options For Countermeasures To the Immunomodulatory Effects mentioning

confidence: 99%

“…Such colostrums, or preparations thereof, reduce STEC shedding by experimentally infected dogs [140] and mitigate Stx2 absorption from the intestine of mice [141]. They protect weaned mice from a lethal dose of STEC O157:H7, avoid the inhibition of water absorption induced by E. coli O157:H7 in human colon fragments, and mitigate the pathogenicity of STEC O157:H7 in rat colon loops, although some of these effects were to be partially attributed to bLF in the preparations [142]. First infections of animals at calf's age coincide with the lack of Stx-specific antibodies.…”

Section: Options For Countermeasures To the Immunomodulatory Effects mentioning

confidence: 99%

See 1 more Smart Citation

The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle

Menge

2020

Toxins

Many cattle are persistently colonized with Shiga toxin-producing Escherichia coli (STEC) and represent a major source of human infections with human-pathogenic STEC strains (syn. enterohemorrhagic E. coli (EHEC)). Intervention strategies most effectively protecting humans best aim at the limitation of bovine STEC shedding. Mechanisms enabling STEC to persist in cattle are only partialy understood. Cattle were long believed to resist the detrimental effects of Shiga toxins (Stxs), potent cytotoxins acting as principal virulence factors in the pathogenesis of human EHEC-associated diseases. However, work by different groups, summarized in this review, has provided substantial evidence that different types of target cells for Stxs exist in cattle. Peripheral and intestinal lymphocytes express the Stx receptor globotriaosylceramide (Gb3syn. CD77) in vitro and in vivo in an activation-dependent fashion with Stx-binding isoforms expressed predominantly at early stages of the activation process. Subpopulations of colonic epithelial cells and macrophage-like cells, residing in the bovine mucosa in proximity to STEC colonies, are also targeted by Stxs. STEC-inoculated calves are depressed in mounting appropriate cellular immune responses which can be overcome by vaccination of the animals against Stxs early in life before encountering STEC. Considering Stx target cells and the resulting effects of Stxs in cattle, which significantly differ from effects implicated in human disease, may open promising opportunities to improve existing yet insufficient measures to limit STEC carriage and shedding by the principal reservoir host.

Front. Cell. Infect. Microbiol.

“…Although the frequency of stool excretion was reduced, the presence of the bacterial toxin was not notably affected (Kuribayashi et al, 2006;Seita et al, 2013). Furthermore, colostral IgG against Shiga toxin and bovine lactoferrin completely prevented lethality of E. coli O157:H7 in a weaned mouse model (Albanese et al, 2018). In addition, an early study in children showed that bovine colostrum is well-tolerated, reduced the frequency of loose stools, and eliminated bacterial infection (Huppertz et al, 1999).…”

Section: Stx-targeted Antibodiesmentioning

confidence: 98%

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

Mühlen

Dersch

2020

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.