Influence of RecA onin vivovirulence and Shiga toxin 2 production inEscherichia colipathogens

Fuchs, Sibylle; Mühldorfer, Inge; Donohue‐Rolfe, Arthur; Kerényi, Mónika; Emödy, Levente; Alexiev, Rossen; Nenkov, P.; Hacker, Jörg

doi:10.1006/mpat.1999.0279

Cited by 78 publications

(67 citation statements)

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“…We established that the spontaneous and the mitomycin C-induced activation of RecA and release of Stx2 were inhibited by NO. Previous studies identified RecA as an important contributor to spontaneous induction of phage release and Stx production (30). Thus, we propose that NO inhibited stx2 mRNA expression in both conditions by a similar mechanism, i.e., the inhibition of RecA activation.…”

Section: Discussionmentioning

confidence: 50%

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Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Vareille¹,

Sablet²,

Hindré³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Shiga-toxin (Stx) is the cardinal virulence factor of enterohemorrhagic Escherichia coli (EHEC). The genes encoding Stx are carried by a lambdoid phage integrated in the bacterial genome and are fully expressed after a bacterial SOS response induced by DNAdamaging agents. Because nitric oxide (NO) is an essential mediator of the innate immune response of infected colonic mucosa, we aimed to determine its role in Stx production by EHEC. Here we demonstrate that chemical or cellular sources of NO inhibit spontaneous and mitomycin C-induced stx mRNA expression and Stx synthesis, without altering EHEC viability. The synthesis of stx phage is also reduced by NO. This inhibitory effect apparently occurs through the NO-mediated sensitization of EHEC because mutation of the NO sensor nitrite-sensitive repressor results in loss of NO inhibiting activity on stx expression. Thus our findings identify NO as an inhibitor of stx expressing-phage propagation and Stx release and thus as a potential protective factor limiting the development of hemolytic syndromes.bacterial infection ͉ mucosal immunology E nterohemorrhagic Escherichia coli (EHEC) are pathogens carried by healthy rearing animals. After infection through the ingestion of contaminated food, EHEC colonize the large intestine and cause gastrointestinal diseases ranging from uncomplicated diarrhea to hemorrhagic colitis. Life-threatening complications, such as hemolytic-uremic syndrome (HUS), develop in Ϸ5-10% of EHEC-infected patients. HUS is defined by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, which can yield to a chronic renal failure and even death (1-3). O157:H7 is the main EHEC serotype implicated in HUS in Europe and North America (3). The few recent large outbreaks (4, 5) underline that prevention of primary infection in human remains an elusive goal. Therefore, understanding host-EHEC interactions remains a critical issue in fighting bacterial infection and HUS development.The main EHEC virulence factor associated with severe human diseases is the Shiga toxin (Stx). Both Stx1 and Stx2 are heteropolymers constituted by a catalytic A subunit and five B subunits implicated in the binding to the receptor glycolipid globotriaosylceramide-3 of endothelial cells. Internalized Stx alters ribosomal function and induces the death of vascular cells (1, 3). Stx1 and Stx2 are encoded by two type lysogenic phages integrated in the bacterial genome (6). In a lysogen, the expression of the phage operons is controlled by the protein CI. As a result of EHEC exposure to DNA-damaging agents such as mitomycin C (7) or H 2 O 2 (8), RecA, which is part of the so-called SOS response, is activated by single-strand DNA and promotes the autocleavage of CI (9). Then, a regulatory cascade yields to the respective expression of the genes encoding the antiterminators N and Q, Stx, and proteins of phage morphogenesis and lysis (9-13). Bacteria are lysed and release Stx and free phage particles in the medium.An important hallmark of EHEC pathoge...

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Section: Discussionmentioning

confidence: 50%

“…Phages were purified as described by Fuchs et al with slight modifications (30). Bacteria culture supernatants (5 ml) were filtered by using 0.2-m filters and incubated with RNase (10 g/ml) and DNase (40 units/ml) for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Vareille¹,

Sablet²,

Hindré³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…It cannot be excluded that the P27 Q gene is replaced by another phage Q homologue by recombination. It is also possible that induction of Stx2e production in the strains is generally triggered by phage-independent functions such as RecA, as previously described for EHEC O157 strains (18).…”

Section: Discussionmentioning

confidence: 87%

Evaluation of Major Types of Shiga Toxin 2e-Producing Escherichia coli Bacteria Present in Food, Pigs, and the Environment as Potential Pathogens for Humans

Beutin¹,

Krüger²,

Krause³

et al. 2008

Appl Environ Microbiol

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Shiga toxin 2e (Stx2e)-producing strains from food (n ‫؍‬ 36), slaughtered pigs (n ‫؍‬ 25), the environment (n ‫؍‬ 21), diseased pigs (n ‫؍‬ 19), and humans (n ‫؍‬ 9) were investigated for production of Stx2e by enzymelinked immunosorbent assay, for virulence markers by PCR, and for their serotypes to evaluate their role as potential human pathogens. Stx2e production was low in 64% of all 110 strains. Stx2e production was inducible by mitomycin C but differed considerably between strains. Analysis by nucleotide sequencing and transcription of stx 2e genes in high-and low-Stx2e-producing strains showed that toxin production correlated with transcription rates of stx 2e genes. DNA sequences specific for the int, Q, dam, and S genes of the stx 2e bacteriophage P27 were found in 109 strains, indicating cryptic P27-like prophages, although 102 of these were not complete for all genes tested. Genes encoding intimin (eae), enterohemorrhagic Escherichia coli hemolysin (ehx), or other stx 1 or stx 2 variants were not found, whereas genes for heat-stable enterotoxins STI, STII, or EAST1 were present in 54.5% of the strains. Seven major serotypes that were associated with diseased pigs (O138:H14, O139:H1, and O141:H4) or with slaughter pigs, food, and the environment (O8:H4, O8:H9, O100:H30, and O101:H9) accounted for 60% of all Stx2e strains. The human Stx2e isolates did not belong to these major serotypes of Stx2e strains, and high production of Stx2e in human strains was not related to diarrheal disease. The results from this study and other studies do not point to Stx2e as a pathogenicity factor for diarrhea and hemolytic uremic syndrome in humans.

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“…Since recA is also a component of the SOS response system which repairs DNA damage, we hypothesize that DNA-damaging agents may be generally considered to induce lambdoid phages. The correlation of phage induction and the SOS response system has been demonstrated for STEC phages by Fuchs et al (1999), who showed the recA dependency on STEC phage induction. The two quinoxaline-1,4-dioxides, carbadox and olaquindox, are able to damage DNA.…”

Section: Discussionmentioning

confidence: 92%

Antibacterials that are used as growth promoters in animal husbandry can affect the release of Shiga-toxin-2-converting bacteriophages and Shiga toxin 2 from Escherichia coli strains

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Influence of RecA onin vivovirulence and Shiga toxin 2 production inEscherichia colipathogens

Cited by 78 publications

References 0 publications

Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Evaluation of Major Types of Shiga Toxin 2e-Producing Escherichia coli Bacteria Present in Food, Pigs, and the Environment as Potential Pathogens for Humans

Antibacterials that are used as growth promoters in animal husbandry can affect the release of Shiga-toxin-2-converting bacteriophages and Shiga toxin 2 from Escherichia coli strains

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