This page has only limited features, please log in for full access.
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.
Christian Menge. The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle. Toxins 2020, 12, 607 .
AMA StyleChristian Menge. The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle. Toxins. 2020; 12 (9):607.
Chicago/Turabian StyleChristian Menge. 2020. "The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle." Toxins 12, no. 9: 607.
Cattle harbor Shiga toxin-producing Escherichia coli (STEC) in their intestinal tract, thereby providing these microorganisms with an ecological niche, but without this colonization leading to any clinical signs. In a preceding study, genotypic characterization of bovine STEC isolates unveiled that their ability to colonize cattle persistently (STECper) or only sporadically (STECspo) is more closely associated with the overall composition of the accessory rather than the core genome. However, the colonization pattern could not be unequivocally linked to the possession of classical virulence genes. This study aimed at assessing, therefore, if the presence of certain phenotypic traits in the strains determines their colonization pattern and if these can be traced back to distinctive genetic features. STECspo strains produced significantly more biofilm than STECper when incubated at lower temperatures. Key substrates, the metabolism of which showed a significant association with colonization type, were glyoxylic acid and L-rhamnose, which were utilized by STECspo, but not or only by some STECper. Genomic sequences of the respective glc and rha operons contained mutations and frameshifts in uptake and/or regulatory genes, particularly in STECper. These findings suggest that STECspo conserved features leveraging survival in the environment, whereas the acquisition of a persistent colonization phenotype in the cattle reservoir was accompanied by the loss of metabolic properties and genomic mutations in the underlying genetic pathways.
Stefanie A. Barth; Michael Weber; Katharina Schaufler; Christian Berens; Lutz Geue; Christian Menge. Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties. Toxins 2020, 12, 414 .
AMA StyleStefanie A. Barth, Michael Weber, Katharina Schaufler, Christian Berens, Lutz Geue, Christian Menge. Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties. Toxins. 2020; 12 (6):414.
Chicago/Turabian StyleStefanie A. Barth; Michael Weber; Katharina Schaufler; Christian Berens; Lutz Geue; Christian Menge. 2020. "Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties." Toxins 12, no. 6: 414.
Shiga toxins (Stxs), syn. Vero(cyto)toxins, are potent bacterial exotoxins and the principal virulence factor of enterohemorrhagic Escherichia coli (EHEC), a subset of Shiga toxin-producing E. coli (STEC). EHEC strains, e.g., strains of serovars O157:H7 and O104:H4, may cause individual cases as well as large outbreaks of life-threatening diseases in humans. Stxs primarily exert a ribotoxic activity in the eukaryotic target cells of the mammalian host resulting in rapid protein synthesis inhibition and cell death. Damage of endothelial cells in the kidneys and the central nervous system by Stxs is central in the pathogenesis of hemolytic uremic syndrome (HUS) in humans and edema disease in pigs. Probably even more important, the toxins also are capable of modulating a plethora of essential cellular functions, which eventually disturb intercellular communication. The review aims at providing a comprehensive overview of the current knowledge of the time course and the consecutive steps of Stx/cell interactions at the molecular level. Intervention measures deduced from an in-depth understanding of this molecular interplay may foster our basic understanding of cellular biology and microbial pathogenesis and pave the way to the creation of host-directed active compounds to mitigate the pathological conditions of STEC infections in the mammalian body.
Christian Menge. Molecular Biology of Escherichia coli Shiga Toxins’ Effects on Mammalian Cells. Toxins 2020, 12, 345 .
AMA StyleChristian Menge. Molecular Biology of Escherichia coli Shiga Toxins’ Effects on Mammalian Cells. Toxins. 2020; 12 (5):345.
Chicago/Turabian StyleChristian Menge. 2020. "Molecular Biology of Escherichia coli Shiga Toxins’ Effects on Mammalian Cells." Toxins 12, no. 5: 345.
The principal virulence factor of Shiga toxin (Stx)-producing Escherichia coli (STEC), the eponymous Stx, modulates cellular immune responses in cattle, the primary STEC reservoir. We examined whether immunization with genetically inactivated recombinant Shiga toxoids (rStx1MUT/rStx2MUT) influences STEC shedding in a calf cohort. A group of 24 calves was passively (colostrum from immunized cows) and actively (intra-muscularly at 5th and 8th week) vaccinated. Twenty-four calves served as unvaccinated controls (fed with low anti-Stx colostrum, placebo injected). Each group was divided according to the vitamin E concentration they received by milk replacer (moderate and high supplemented). The effective transfer of Stx-neutralizing antibodies from dams to calves via colostrum was confirmed by Vero cell assay. Serum antibody titers in calves differed significantly between the vaccinated and the control group until the 16th week of life. Using the expression of activation marker CD25 on CD4+CD45RO+ cells and CD8αhiCD45RO+ cells as flow cytometry based read-out, cells from vaccinated animals responded more pronounced than those of control calves to lysates of STEC and E. coli strains isolated from the farm as well as to rStx2MUT in the 16th week. Summarized for the entire observation period, less fecal samples from vaccinated calves were stx1 and/or stx2 positive than samples from control animals when calves were fed a moderate amount of vitamin E. This study provides first evidence, that transfer to and induction in young calves of Stx-neutralizing antibodies by Shiga toxoid vaccination offers the opportunity to reduce the incidence of stx-positive fecal samples in a calf cohort.
Nadine Schmidt; Stefanie A. Barth; Jana Frahm; Ulrich Meyer; Sven Dänicke; Lutz Geue; Christian Menge. Decreased STEC shedding by cattle following passive and active vaccination based on recombinant Escherichia coli Shiga toxoids. Veterinary Research 2018, 49, 1 -15.
AMA StyleNadine Schmidt, Stefanie A. Barth, Jana Frahm, Ulrich Meyer, Sven Dänicke, Lutz Geue, Christian Menge. Decreased STEC shedding by cattle following passive and active vaccination based on recombinant Escherichia coli Shiga toxoids. Veterinary Research. 2018; 49 (1):1-15.
Chicago/Turabian StyleNadine Schmidt; Stefanie A. Barth; Jana Frahm; Ulrich Meyer; Sven Dänicke; Lutz Geue; Christian Menge. 2018. "Decreased STEC shedding by cattle following passive and active vaccination based on recombinant Escherichia coli Shiga toxoids." Veterinary Research 49, no. 1: 1-15.
Ruminants are the main source of human infections with the obligate intracellular bacterium Coxiella (C.) burnetii. Infected animals shed high numbers of C. burnetii by milk, feces, and birth products. In goats, shedding by the latter route coincides with C. burnetii replication in epithelial (trophoblast) cells of the placenta, which led us to hypothesize that epithelial cells are generally implicated in replication and shedding of C. burnetii. We therefore aimed at analyzing the interactions of C. burnetii with epithelial cells of the bovine host (1) at the entry site (lung epithelium) which govern host immune responses and (2) in epithelial cells of gut, udder and placenta decisive for the quantity of pathogen excretion. Epithelial cell lines [PS (udder), FKD-R 971 (small intestine), BCEC (maternal placenta), F3 (fetal placenta), BEL-26 (lung)] were inoculated with C. burnetii strains Nine Mile I (NMI) and NMII at different cultivation conditions. The cell lines exhibited different permissiveness for C. burnetii. While maintaining cell viability, udder cells allowed the highest replication rates with formation of large cell-filling Coxiella containing vacuoles. Intestinal cells showed an enhanced susceptibility to invasion but supported C. burnetii replication only at intermediate levels. Lung and placental cells also internalized the bacteria but in strikingly smaller numbers. In any of the epithelial cells, both Coxiella strains failed to trigger a substantial IL-1β, IL-6 and TNF-α response. Epithelial cells, with mammary epithelial cells in particular, may therefore serve as a niche for C. burnetii replication in vivo without alerting the host’s immune response.
Katharina Sobotta; Katharina Bonkowski; Elisabeth Liebler-Tenorio; Pierre Germon; Pascal Rainard; Nina Hambruch; Christiane Pfarrer; Ilse D. Jacobsen; Christian Menge. Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii. Veterinary Research 2017, 48, 1 -15.
AMA StyleKatharina Sobotta, Katharina Bonkowski, Elisabeth Liebler-Tenorio, Pierre Germon, Pascal Rainard, Nina Hambruch, Christiane Pfarrer, Ilse D. Jacobsen, Christian Menge. Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii. Veterinary Research. 2017; 48 (1):1-15.
Chicago/Turabian StyleKatharina Sobotta; Katharina Bonkowski; Elisabeth Liebler-Tenorio; Pierre Germon; Pascal Rainard; Nina Hambruch; Christiane Pfarrer; Ilse D. Jacobsen; Christian Menge. 2017. "Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii." Veterinary Research 48, no. 1: 1-15.
In 2011, a severe outbreak of hemolytic-uremic syndrome was caused by an unusual, highly virulent enterohemorrhagic E. coli (EHEC) O104:H4 strain, which possessed EHEC virulence traits in the genetic background of human-adapted enteroaggregative E. coli. To determine magnitude of fecal shedding and site of colonization of EHEC O104:H4 in a livestock host, 30 (ten/strain) weaned calves were inoculated with 1010 CFU of EHEC O104:H4, EHEC O157:H7 (positive control) or E. coli strain 123 (negative control) and necropsied (4 or 28 d.p.i.). E. coli O157:H7 was recovered until 28 d.p.i. and O104:H4 until 24 d.p.i. At 4 d.p.i., EHEC O104:H4 was isolated from intestinal content and detected associated with the intestinal mucosa. These results are the first evidence that cattle, the most important EHEC reservoir, can also carry unusual EHEC strains at least transiently, questioning our current understanding of the molecular basis of host adaptation of this important E. coli pathovar.
K. Hamm; Stefanie Barth; S. Stalb; L. Geue; E. Liebler-Tenorio; J. P. Teifke; E. Lange; K. Tauscher; G. Kotterba; M. Bielaszewska; H. Karch; C. Menge. Experimental Infection of Calves with Escherichia coli O104:H4 outbreak strain. Scientific Reports 2016, 6, 32812 .
AMA StyleK. Hamm, Stefanie Barth, S. Stalb, L. Geue, E. Liebler-Tenorio, J. P. Teifke, E. Lange, K. Tauscher, G. Kotterba, M. Bielaszewska, H. Karch, C. Menge. Experimental Infection of Calves with Escherichia coli O104:H4 outbreak strain. Scientific Reports. 2016; 6 (1):32812.
Chicago/Turabian StyleK. Hamm; Stefanie Barth; S. Stalb; L. Geue; E. Liebler-Tenorio; J. P. Teifke; E. Lange; K. Tauscher; G. Kotterba; M. Bielaszewska; H. Karch; C. Menge. 2016. "Experimental Infection of Calves with Escherichia coli O104:H4 outbreak strain." Scientific Reports 6, no. 1: 32812.