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Matthew K Waldor - One of the best experts on this subject based on the ideXlab platform.

  • shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia Coli
    PLOS Pathogens, 2021
    Co-Authors: Alyson R Warr, Carole J Kuehl, Matthew K Waldor
    Abstract:

    Enterohemorrhagic Escherichia Coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that Stx potently remodels the host innate immune response to EHEC.

  • shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia Coli
    bioRxiv, 2020
    Co-Authors: Alyson R Warr, Carole J Kuehl, Matthew K Waldor
    Abstract:

    Abstract Enterohemorrhagic Escherichia Coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that within the intestine, Stx primarily targets epithelial cells, and that the potent Stx-mediated modulation of innate immune signaling skews the host response to EHEC towards type 3 immunity. Significance Statement Enterohemorrhagic Escherichia Coli (EHEC) is a potentially lethal foodborne pathogen. During infection, EHEC releases a potent toxin, Shiga toxin (Stx), into the intestine, but there is limited knowledge of how this toxin shapes the host response to infection. We used an infant rabbit model of infection that closely mimics human disease to profile intestinal transcriptomic responses to EHEC infection. Comparisons of the transcriptional responses to infection by strains containing or lacking Stx revealed that this toxin markedly remodels how the epithelial cell compartment responds to infection. Our findings suggest that Stx biases the intestinal innate immune response to EHEC and provide insight into the complex host-pathogen dialogue that underlies disease.

  • dam methyltransferase is required for stable lysogeny of the shiga toxin stx2 encoding bacteriophage 933w of Enterohemorrhagic Escherichia Coli o157 h7
    Journal of Bacteriology, 2008
    Co-Authors: Kenan C Murphy, Jennifer M Ritchie, Matthew K Waldor, Anders Lobnerolesen, Martin G Marinus
    Abstract:

    Shiga toxin 2 (Stx2), one of the principal virulence factors of Enterohemorrhagic Escherichia Coli, is encoded by 933W, a lambda-like prophage. 933W prophage induction contributes to Stx2 production, and here, we provide evidence that Dam methyltransferase is essential for maintenance of 933W lysogeny. Our findings are consistent with the idea that the 933W prophage has a relatively low threshold for induction, which may promote Stx2 production during infection.

Robert A Britton - One of the best experts on this subject based on the ideXlab platform.

  • probiotic lactobacillus reuteri ameliorates disease due to Enterohemorrhagic Escherichia Coli in germfree mice
    Infection and Immunity, 2011
    Co-Authors: Kathryn A Eaton, Alexander Honkala, Thomas A Auchtung, Robert A Britton
    Abstract:

    Strains of Enterohemorrhagic Escherichia Coli (EHEC) are a group of Shiga toxin-producing food-borne pathogens that cause severe hemorrhagic Colitis and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affects children and for which there is no effective treatment. We used a germfree mouse model of renal and enteric disease due to EHEC to determine if probiotic Lactobacillus reuteri ATCC PTA 6475 is effective in suppressing disease symptoms caused by EHEC. When germfree Swiss Webster mice are monocolonized with EHEC, they develop disease characterized by weight loss, cecal luminal fluid accumulation, and renal tubular necrosis. When L. reuteri was administered 1 day prior to EHEC challenge and every other day thereafter, EHEC colonization was suppressed and mice were significantly protected from the manifestations of disease. Protection from disease did not require the induction of the antimicrobial compound reuterin in L. reuteri prior to treatment. The twice-daily administration of L. reuteri appeared more effective than every-other-day administration. These data indicated that L. reuteri partially protects mice from disease manifestations of EHEC. Strains of Enterohemorrhagic Escherichia Coli (EHEC) are food-borne bacterial pathogens of humans that are normal inhabitants of the ruminant intestine (4). These organisms often are transmitted to humans in undercooked meat but also

  • probiotic lactobacillus reuteri ameliorates disease due to Enterohemorrhagic Escherichia Coli in germfree mice
    Infection and Immunity, 2011
    Co-Authors: Kathryn A Eaton, Alexander Honkala, Thomas A Auchtung, Robert A Britton
    Abstract:

    Strains of Enterohemorrhagic Escherichia Coli (EHEC) are a group of Shiga toxin-producing food-borne pathogens that cause severe hemorrhagic Colitis and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affects children and for which there is no effective treatment. We used a germfree mouse model of renal and enteric disease due to EHEC to determine if probiotic Lactobacillus reuteri ATCC PTA 6475 is effective in suppressing disease symptoms caused by EHEC. When germfree Swiss Webster mice are monocolonized with EHEC, they develop disease characterized by weight loss, cecal luminal fluid accumulation, and renal tubular necrosis. When L. reuteri was administered 1 day prior to EHEC challenge and every other day thereafter, EHEC colonization was suppressed and mice were significantly protected from the manifestations of disease. Protection from disease did not require the induction of the antimicrobial compound reuterin in L. reuteri prior to treatment. The twice-daily administration of L. reuteri appeared more effective than every-other-day administration. These data indicated that L. reuteri partially protects mice from disease manifestations of EHEC.

Kathryn A Eaton - One of the best experts on this subject based on the ideXlab platform.

  • probiotic lactobacillus reuteri ameliorates disease due to Enterohemorrhagic Escherichia Coli in germfree mice
    Infection and Immunity, 2011
    Co-Authors: Kathryn A Eaton, Alexander Honkala, Thomas A Auchtung, Robert A Britton
    Abstract:

    Strains of Enterohemorrhagic Escherichia Coli (EHEC) are a group of Shiga toxin-producing food-borne pathogens that cause severe hemorrhagic Colitis and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affects children and for which there is no effective treatment. We used a germfree mouse model of renal and enteric disease due to EHEC to determine if probiotic Lactobacillus reuteri ATCC PTA 6475 is effective in suppressing disease symptoms caused by EHEC. When germfree Swiss Webster mice are monocolonized with EHEC, they develop disease characterized by weight loss, cecal luminal fluid accumulation, and renal tubular necrosis. When L. reuteri was administered 1 day prior to EHEC challenge and every other day thereafter, EHEC colonization was suppressed and mice were significantly protected from the manifestations of disease. Protection from disease did not require the induction of the antimicrobial compound reuterin in L. reuteri prior to treatment. The twice-daily administration of L. reuteri appeared more effective than every-other-day administration. These data indicated that L. reuteri partially protects mice from disease manifestations of EHEC. Strains of Enterohemorrhagic Escherichia Coli (EHEC) are food-borne bacterial pathogens of humans that are normal inhabitants of the ruminant intestine (4). These organisms often are transmitted to humans in undercooked meat but also

  • probiotic lactobacillus reuteri ameliorates disease due to Enterohemorrhagic Escherichia Coli in germfree mice
    Infection and Immunity, 2011
    Co-Authors: Kathryn A Eaton, Alexander Honkala, Thomas A Auchtung, Robert A Britton
    Abstract:

    Strains of Enterohemorrhagic Escherichia Coli (EHEC) are a group of Shiga toxin-producing food-borne pathogens that cause severe hemorrhagic Colitis and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affects children and for which there is no effective treatment. We used a germfree mouse model of renal and enteric disease due to EHEC to determine if probiotic Lactobacillus reuteri ATCC PTA 6475 is effective in suppressing disease symptoms caused by EHEC. When germfree Swiss Webster mice are monocolonized with EHEC, they develop disease characterized by weight loss, cecal luminal fluid accumulation, and renal tubular necrosis. When L. reuteri was administered 1 day prior to EHEC challenge and every other day thereafter, EHEC colonization was suppressed and mice were significantly protected from the manifestations of disease. Protection from disease did not require the induction of the antimicrobial compound reuterin in L. reuteri prior to treatment. The twice-daily administration of L. reuteri appeared more effective than every-other-day administration. These data indicated that L. reuteri partially protects mice from disease manifestations of EHEC.

  • pathogenesis of renal disease due to Enterohemorrhagic Escherichia Coli in germ free mice
    Infection and Immunity, 2008
    Co-Authors: Kathryn A Eaton, David I Friedman, Gayle J Francis, Jessica S Tyler, Vincent B Young, Jennifer Haeger, Galeb Abuali, Thomas S Whittam
    Abstract:

    Enterohemorrhagic Escherichia Coli (EHEC) is a food-borne pathogen that causes hemorrhagic Colitis and acute renal failure. We used a germ-free mouse model to investigate the role of host factors, Shiga toxin 2 (Stx2), and bacterial strain in disease due to EHEC. Germ-free male and female Swiss-Webster mice that were 3 days to 12 weeks old were orally inoculated with 1 of 10 EHEC strains or derivatives of two of these strains with Stx2 deleted. All inoculated mice became infected regardless of the inoculum dose. All bacterial strains colonized the intestines, reaching levels of 109 to 1012 CFU/g of feces by 4 days after inoculation. Seven of the 10 wild-type strains caused disease. However, the two Stx2 deletion mutants, unlike the Stx2+ parental strains, did not cause disease. The clinical signs of disease in mice included lethargy, dehydration, polyuria, polydypsia, and death. Postmortem examination of affected mice revealed dehydration and luminal cecal fluid accumulation. Histologic examination revealed close adherence of bacteria to the intestinal epithelium in the ileum and cecum but not in the colon. Other lesions included progressive renal tubular necrosis, glomerular fibrin thrombosis, and red blood cell sludging. The severity of disease varied according to the bacterial strain and age, but not sex, of the host. This study demonstrated that EHEC colonizes germ-free mice in large numbers, adheres to the intestinal epithelium, and causes luminal cecal fluid accumulation and progressive renal failure. The disease in mice was Stx2 and bacterial strain dependent. This animal model should be a useful tool for studying the pathogenesis of renal disease secondary to EHEC infection.

Helge Karch - One of the best experts on this subject based on the ideXlab platform.

  • Enterohemorrhagic Escherichia Coli o26 h11 associated hemolytic uremic syndrome bacteriology and clinical presentation
    Seminars in Thrombosis and Hemostasis, 2010
    Co-Authors: Lotharbernd Zimmerhackl, Alexander Mellmann, Martina Bielaszewska, Alejandra Rosales, Johannes Hofer, Magdalena Riedl, Therese Jungraithmayr, Helge Karch
    Abstract:

    : Infection by Enterohemorrhagic Escherichia Coli (EHEC) is the most frequent cause of hemolytic uremic syndrome (HUS) in childhood. During a 6-year period, all patients with the clinical diagnosis of HUS were registered in a prospective multicenter study in Austria and Germany. EHEC O26:H11 was the second most frequent detected serotype, accounting for 15.4% of all EHEC isolates. The presence of EHEC O26:H11 was significantly associated with young age at the disease onset ( P < 0.001). Patients infected with this serotype were not different in their clinical presentation than those infected with other serotypes. This study underlines the importance of EHEC serotypes other than O157 in the etiology of HUS and emphasizes the importance of implementation of appropriate diagnostic methods to identify the whole spectrum of EHEC associated with HUS.

  • analysis of collection of hemolytic uremic syndrome associated Enterohemorrhagic Escherichia Coli
    Emerging Infectious Diseases, 2008
    Co-Authors: Alexander Mellmann, Martina Bielaszewska, Robin Kock, Alexander W Friedrich, Angelika Fruth, Barbara Middendorf, Dag Harmsen, Alexander M Schmidt, Helge Karch
    Abstract:

    Multilocus sequence typing of 169 non-O157 Enterohemorrhagic Escherichia Coli (EHEC) isolated from patients with hemolytic uremic syndrome (HUS) demonstrated 29 different sequence types (STs); 78.1% of these strains clustered in 5 STs. From all STs and serotypes identified, we established a reference panel of EHEC associated with HUS (HUSEC collection).

  • Enterohemorrhagic Escherichia Coli in human infection in vivo evolution of a bacterial pathogen
    Clinical Infectious Diseases, 2005
    Co-Authors: Alexander Mellmann, Martina Bielaszewska, Dag Harmsen, Lothar B Zimmerhackl, Rita Prager, Helmut Tschape, Helge Karch
    Abstract:

    Background. Enterohemorrhagic Escherichia Coli (EHEC) cause most cases of the hemolytic uremic syndrome (HUS) worldwide. To investigate genetic changes in EHEC during the course of human infection, we analyzed consecutive stool samples and shed isolates from patients with HUS, focusing on the genes encoding Shiga toxin (stx) and intimin (eae). Methods. Sequential stool samples from 210 patients with HUS were investigated for the persistence of E. Coli strains harboring stx and/or eae. Initial stool samples were collected during the acute phase of HUS, and subsequent stool samples were collected 3-16 days later (median interval, 8 days). Results. Organisms that were stx and eae positive (stx+/eae+ strains; n = 137) or stx negative and eae positive (stx-/eae+ strains; n = 5) were detected in the initial stool samples from 142 patients. Subsequently, the proportion of those who shed stx+/eae+ strains decreased to 13 of 210 patients, whereas the proportion of those who shed strains that were stx-/eae+ increased to 12 of 210 patients. Seven patients who initially excreted strains that were stx+/eae+ shed, at second analysis, stx-/eae+ strains of the same serotypes; they had no free fecal Shiga toxin at follow-up. Comparison of the initial and follow-up isolates from these patients with use of molecular-epidemiological methods revealed loss of stx genes and genomic rearrangement. Conclusions. We demonstrate the loss of a critical bacterial virulence factor from pathogens during very brief intervals in the human host. These genetic changes have evolutionary, diagnostic, and clinical implications. Generation of stx- mutants might contribute to subclonal evolution and evolutionary success.

  • phenotypic and molecular analysis of tellurite resistance among Enterohemorrhagic Escherichia Coli o157 h7 and sorbitol fermenting o157 nm clinical isolates
    Journal of Clinical Microbiology, 2005
    Co-Authors: Martina Bielaszewska, Helge Karch, Phillip I Tarr, Wenlan Zhang, Werner Mathys
    Abstract:

    A total of 66 (98.5%) of 67 Enterohemorrhagic Escherichia Coli (EHEC) O157:H7 strains had increased potassium tellurite (Te) MICs (32 to 1,024 μg/ml), grew on Te-containing media, and possessed Te resistance (ter) genes, whereas 83 (96.5%) of 86 sorbitol-fermenting (SF) EHEC O157:NM strains had Te MICs of ≤4 μg/ml, did not grow on Te-containing media, and lacked ter genes. Optimal detection of SF EHEC O157:NM strains requires Te-independent strategies.

  • phenotypic and genotypic analyses of Enterohemorrhagic Escherichia Coli o145 strains from patients in germany
    Journal of Clinical Microbiology, 2004
    Co-Authors: Annekatharina Sonntag, Martina Bielaszewska, Angelika Fruth, Wenlan Zhang, Rita Prager, Helmut Tschape, Helge Karch
    Abstract:

    Enterohemorrhagic Escherichia Coli (EHEC) strains of serogroup O145 are emerging as causes of diarrhea and the hemolytic-uremic syndrome. However, there have been few genetic analyses of this EHEC group. We investigated the serotypes, virulence genes, plasmid profiles, pulsed-field gel electrophoresis (PFGE) patterns, and genetic variability of the fliC and eae genes in 120 EHEC O145 strains isolated from cases of hemolytic-uremic syndrome (n = 24) or diarrhea (n = 96) in Germany between 1996 and 2002. Three isolates belonged to serotype O145:H28, one to serotype O145:H25, and 116 were nonmotile (O145:H(-)). One hundred fourteen of the nonmotile strains shared fliC restriction fragment length polymorphism (RFLP) patterns identical to that of the O145:H28 strains. The remaining two nonmotile strains displayed a fliC-RFLP pattern identical to that of the O145:H25 strain. Each of the 117 strains with the fliC-RFLP(H28) pattern harbored eae gamma, whereas the three strains with the fliC-RFLP(H25) pattern possessed eae beta. Five different stx genotypes, six combinations of plasmid-encoded putative virulence genes, 29 plasmid profiles, and 47 PFGE types were identified. Strains within some of the PFGE types could be further subtyped by means of distinct plasmid profiles. These data demonstrate that the EHEC O145 serogroup is comprised of two different serotypes that possess distinct eae types. The heterogeneity of EHEC O145 strains at the chromosomal and plasmid level, in particular the high diversity in PFGE patterns, provides a basis for molecular subtyping of these pathogens.

Sunao Iyoda - One of the best experts on this subject based on the ideXlab platform.

  • rna binding protein hfq downregulates locus of enterocyte effacement encoded regulators independent of small regulatory rna in Enterohemorrhagic Escherichia Coli
    Molecular Microbiology, 2021
    Co-Authors: Naoki Sudo, Makoto Ohnishi, Kenichi Lee, Yasuhiko Sekine, Sunao Iyoda
    Abstract:

    Enterohemorrhagic Escherichia Coli (EHEC) causes severe human diseases worldwide. The type three secretion system and effector proteins are essential for EHEC infection, and are encoded by the locus of enterocyte effacement (LEE). RNA-binding protein Hfq is essential for small regulatory RNA (sRNA)-mediated regulation at a post-transcriptional level and full virulence of many pathogenic bacteria. Although two early studies indicated that Hfq represses LEE expression by post-transcriptionally controlling the expression of genes grlRA and/or ler, both of which encode LEE regulators mediating a positive regulatory loop, the detailed molecular mechanism and biological significance remain unclear. Herein, we show that LEE overexpression was caused by defective RNA-binding activity of the Hfq distal face, which post-transcriptionally represses grlA and ler expression. In vitro analyses revealed that the Hfq distal face directly binds near the translational initiation site of grlA and ler mRNAs, and inhibits their translation. Taken together, we conclude that Hfq inhibits grlA and ler translation by binding their mRNAs through the distal face in an sRNA-independent manner. Additionally, we show that Hfq-mediated repression of LEE is critical for normal EHEC growth because all suppressor mutations that restored the growth defect in the hfq mutant abolished hfq deletion-induced overexpression of LEE.

  • complete genome sequence of an Enterohemorrhagic Escherichia Coli o111 h8 strain recovered from a large outbreak in japan associated with consumption of raw beef
    Microbiology Resource Announcements, 2019
    Co-Authors: Tsuyoshi Sekizuka, Sunao Iyoda, Kenichi Lee, Keiko Kimata, Junko Isobe, Makoto Kuroda, Makoto Ohnishi, Tetsutaro Sata, Masanori Watahiki
    Abstract:

    ABSTRACT We present the complete genome sequence of an Enterohemorrhagic Escherichia Coli O111:H8 strain. This strain was isolated from a hemolytic-uremic syndrome patient and was responsible for a large outbreak associated with the consumption of raw beef in 2011.

  • effective surveillance using multilocus variable number tandem repeat analysis and whole genome sequencing for Enterohemorrhagic Escherichia Coli o157
    Applied and Environmental Microbiology, 2019
    Co-Authors: Kenichi Lee, Sunao Iyoda, Hidemasa Izumiya, Makoto Ohnishi
    Abstract:

    Due to the potential of Enterohemorrhagic Escherichia Coli (EHEC) serogroup O157 to cause large foodborne outbreaks, national and international surveillance is necessary. For developing an effective method of molecular surveillance, conventional multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS) analysis were compared. WGS of 369 isolates of EHEC O157 belonging to seven major MLVA types and their relatives were subjected to comprehensive in silico typing, core genome (cg)SNP, and cgMLST analyses. The typing resolution was the highest in cgSNP analysis. However, determination of the sequence of the mismatch repair protein gene mutS is necessary because spontaneous deletion of the gene could lead to a hypermutator phenotype. MLVA had sufficient typing resolution for a short-term outbreak investigation and had advantages in rapidity and high throughput. cgMLST showed less typing resolution than cgSNP, but it is less time-consuming and does not require as much computer power. Therefore, cgMLST is suitable for comparisons using large datasets (e.g., international comparison using public databases). In conclusion, screening using MLVA followed by cgMLST and cgSNP analyses would provide the highest typing resolution and improve the accuracy and cost-effectiveness of EHEC surveillance. Importance Intensive surveillance for Enterohemorrhagic Escherichia Coli (EHEC) serogroup O157 is important to detect outbreaks and to prevent the spread of the bacterium. Recent advances in sequencing technology made molecular surveillance using whole genome sequence (WGS) realistic. To develop rapid, high-throughput, and cost-effective typing methods for real-time surveillance, typing resolution of WGS and a conventional typing method, multilocus variable number tandem repeat analysis (MLVA), was evaluated. Nation-level systematic comparison of MLVA, cgSNP, and cgMLST indicated that a combination of WGS and MLVA is a realistic approach to improve EHEC surveillance.

  • identification of a new virulent clade in Enterohemorrhagic Escherichia Coli o26 h11 h sequence type 29
    Scientific Reports, 2017
    Co-Authors: Nozomi Ishijima, Kenichi Lee, Makoto Ohnishi, Yoshitoshi Ogura, Tetsuya Hayashi, Atsushi Iguchi, Tomomi Kuwahara, Haruyuki Nakayamaimaohji, Saori Yoneda, Sunao Iyoda
    Abstract:

    Enterohemorrhagic Escherichia Coli (EHEC) O26 infections cause severe human diseases such as hemolytic uremic syndrome and encephalopathy, and is the predominant serogroup among non-O157 EHEC in many countries. Shiga toxin (Stx), which consists of two distinct types (Stx1 and Stx2), plays a central role in EHEC pathogenesis. The major stx gene type in EHEC O26 strains is stx1, although isolates with only stx2 have emerged in Japan since 2012 and have been reported in Europe. In this study, we selected 27 EHEC O26 strains isolated in Japan and identified a distinct genetic clade within sequence type (ST) 29, designated ST29C1, that carried only stx2 and had the plasmid gene profile ehxA+/katP-/espP+/etpD-. We showed that ST29C1 strains produced higher Stx2a levels, and greater virulence in Vero cells and in germ-free mice than other lineages. We also showed that ST29C1 was a distinct phylogenetic clade by SNP analysis using whole genome sequences and clearly differed from the major European EHEC O26 virulent clone, which was designated ST29C2 in this study. The combination of toxin production analysis, virulence analysis in Vero cells and germ-free mice, and phylogenetic analysis identified a newly emerging virulent EHEC clade.

  • lipopolysaccharide o antigen of Enterohemorrhagic Escherichia Coli o157 h7 is required for killing both insects and mammals
    Fems Microbiology Letters, 2012
    Co-Authors: Atsushi Miyashita, Kazuhisa Sekimizu, Kenichi Ishii, Hiroshi Hamamoto, Sunao Iyoda, Chikara Kaito
    Abstract:

    Studies of Enterohemorrhagic Escherichia Coli (EHEC) infection mechanisms using mammals require large numbers of animals and are both costly and associated with ethical problems. Here, we evaluated the pathogenic mechanisms of EHEC in the silkworm model. Injection of a clinically isolated EHEC O157:H7 Sakai into either the silkworm hemolymph or intraperitoneal fluid of mice killed the host animals. EHEC O157:H7 Sakai deletion mutants of the rfbE gene, which encodes perosamine synthetase, a monosaccharide component synthetase of the O-antigen, or deletion mutants of the waaL gene, which encodes O-antigen ligase against the lipid A-core region of lipopolysaccharide (LPS), had attenuated killing ability in both silkworms and mice. Introduction of the rfbE gene or the waaL gene into the respective mutants restored the killing ability in silkworms. Growth of both mutants was inhibited by a major antimicrobial peptide in the silkworm hemolymph, moricin. The viability of both mutants was decreased in swine serum. The bactericidal effect of swine serum against both mutants was inactivated by heat treatment. These findings suggest that the LPS O-antigen of EHEC O157:H7 plays an important defensive role against antimicrobial factors in the host body fluid and is thus essential to the lethal effects of EHEC in animals.