OMV-based vaccine formulations against Shiga toxin producing<i>Escherichia coli</i>strains are both protective in mice and immunogenic in calves

Fingermann, Matías; Ávila, Lucía; Marco, Maria Belén De; Vázquez, Luciana; Biase, Darío Nicolás Di; Müller, A.; Lescano, Mirta; Dokmetjian, José Christian; Castillo, Sonsire Fernández; Quiñoy, José Luis Pérez

doi:10.1080/21645515.2018.1490381

Cited by 22 publications

(22 citation statements)

References 47 publications

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“…Targeting outer membrane vesicles (OMVs) produced by E. coli O157:H7 has been successfully explored using eyedrop administration in mice [94]. More recently, approaches targeting OMVs have also been tested in cattle and proved effective, providing encouraging results for future human use [95].…”

Section: Potential Future Therapiesmentioning

confidence: 99%

Shiga-Toxin E. coli Hemolytic Uremic Syndrome: Review of Management and Long-term Outcome

2020

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Purpose of Review We review the pathophysiology of Shiga-Toxin Enteropathogenic-Hemolytic Uremic Syndrome (STEC-HUS), strategies to ameliorate or prevent evolution of STEC-HUS, management and the improved recognition of long-term adverse outcomes. Recent Findings Following on from the preclinical evidence of a role for the complement system in STEC-HUS, the use of complement blocking agents has been the major focus of most recent clinical research. Novel therapies to prevent or lessen HUS have yet to enter the clinical arena. The long-term outcomes of STEC-HUS, similarly to other causes of AKI, are not as benign as previously thought. Summary Optimizing supportive care in STEC-HUS is the only current recommended treatment. The administration of early isotonic fluids may reduce the severity and duration of STEC-HUS. The role of complement blockade in the management of STEC-HUS remains unclear. The long-term sequelae from STEC-HUS are significant and patients with apparent full renal recovery remain at risk.

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Section: Potential Future Therapiesmentioning

confidence: 99%

Shiga-Toxin E. coli Hemolytic Uremic Syndrome: Review of Management and Long-term Outcome

2020

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“…components of vaccines since they combine the antigen and adjuvant in a single formulation. A vaccine based on OMVs of a major EHEC serotype O157:H7 was found to protect against EHEC-mediated pathology in a mouse model and to be immunogenic in calves (Fingermann et al, 2018). These initial studies suggest that EHEC-derived OMVs have a potential for the formulation of both human and veterinary vaccines.…”

Section: Discussionmentioning

confidence: 98%

Secretion and Delivery of Intestinal Pathogenic Escherichia coli Virulence Factors via Outer Membrane Vesicles

Rueter

Bielaszewska

2020

Front. Cell. Infect. Microbiol.

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Outer membrane vesicles (OMVs) are nanoscale proteoliposomes secreted from the cell envelope of all Gram-negative bacteria. Originally considered as an artifact of the cell wall, OMVs are now recognized as a general secretion system, which serves to improve the fitness of bacteria and facilitate bacterial interactions in polymicrobial communities as well as interactions between the microbe and the host. In general, OMVs are released in increased amounts from pathogenic bacteria and have been found to harbor much of the contents of the parental bacterium. They mainly encompass components of the outer membrane and the periplasm including various virulence factors such as toxins, adhesins, and immunomodulatory molecules. Numerous studies have clearly shown that the delivery of toxins and other virulence factors via OMVs essentially influences their interactions with host cells. Here, we review the OMV-mediated intracellular deployment of toxins and other virulence factors with a special focus on intestinal pathogenic Escherichia coli. Especially, OMVs ubiquitously produced and secreted by enterohemorrhagic E. coli (EHEC) appear as a highly advanced mechanism for secretion and simultaneous, coordinated and direct delivery of bacterial virulence factors into host cells. OMV-associated virulence factors are not only stabilized by the association with OMVs, but can also often target previously unknown target structures and perform novel activities. The toxins are released by OMVs in their active forms and are transported via cell sorting processes to their specific cell compartments, where they can develop their detrimental effects. OMVs can be considered as bacterial "long distance weapons" that attack host tissues and help bacterial pathogens to establish the colonization of their biological niche(s), impair host cell function, and modulate the defense of the host. Thus, OMVs contribute significantly to the virulence of the pathogenic bacteria.

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“…Here, mice were immunized subcutaneously on days 0 and 21 and received an intraperitoneal challenge with concentrated cell supernatants 2 weeks after application of second immunization. While 90% of control mice died by day seven post-challenge, all immunized mice survived (Fingermann et al, 2018).…”

Section: Outer Membrane Vesiclesmentioning

confidence: 96%

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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OMV-based vaccine formulations against Shiga toxin producingEscherichia colistrains are both protective in mice and immunogenic in calves

Cited by 22 publications

References 47 publications

Shiga-Toxin E. coli Hemolytic Uremic Syndrome: Review of Management and Long-term Outcome

Shiga-Toxin E. coli Hemolytic Uremic Syndrome: Review of Management and Long-term Outcome

Secretion and Delivery of Intestinal Pathogenic Escherichia coli Virulence Factors via Outer Membrane Vesicles

Treatment Strategies for Infections With Shiga Toxin-Producing Escherichia coli

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