title: Virulence of the Shiga toxin type 2-expressing Escherichia coli O104:H4 German outbreak isolate in two animal models.
abstract: In May 2011, a large food-borne outbreak was traced to an unusual O104:H4 enteroaggregative Escherichia coli (EAEC) strain that produced Shiga toxin (Stx) type 2 (Stx2). We developed a mouse model to study the pathogenesis and treatment for this strain and examined the virulence of the isolate for Dutch belted rabbits. O104:H4 strain C227-11 was gavaged into C57BL/6 mice at 10(9) to 10(11) CFU/animal. The infected animals were then given water with ampicillin (Amp; 5 g/liter) ad libitum. The C227-11-infected, Amp-treated C57BL/6 mice exhibited both morbidity and mortality. Kidneys from mice infected with C227-11 showed acute tubular necrosis, a finding seen in mice infected with typical Stx-producing E. coli. We provided anti-Stx2 antibody after infection and found that all of the antibody-treated mice gained more weight than untreated mice and, in another study, that all of the antibody-treated animals lived, whereas 3/8 phosphate-buffered saline-treated mice died. We further compared the pathogenesis of C227-11 with that of an Stx-negative (Stx(-)) O104:H4 isolate, C734-09, and an Stx2(-) phage-cured derivative of C227-11. Whereas C227-11-infected animals lost weight or gained less weight over the course of infection and died, mice infected with either of the Stx(-) isolates did not lose weight and only one mouse died. When the Stx-positive (Stx(+)) and Stx2(-) O104:H4 strains were compared in rabbits, greater morbidity and mortality were observed in rabbits infected with the Stx2(+) isolates than the Stx2(-) isolates. In conclusion, we describe two animal models for EAEC pathogenesis, and these studies show that Stx2 is responsible for most of the virulence observed in C227-11-infected mice and rabbits.
authors: Uniformed Services University of Health Sciences, Department of Microbiology and Immunology, Bethesda, Maryland, USA.
authors: Tonia
authors: T
authors: Zangari
authors: Angela R
authors: AR
authors: Melton-Celsa
authors: Aruna
authors: A
authors: Panda
authors: Nadia
authors: N
authors: Boisen
authors: Mark A
authors: MA
authors: Smith
authors: Ivan
authors: I
authors: Tatarov
authors: Louis J
authors: LJ
authors: De Tolla
authors: James P
authors: JP
authors: Nataro
authors: Alison D
authors: AD
authors: O'Brien
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D005858:Germany / Q000453:epidemiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D022641:Shiga Toxin 2 / Q000378:metabolism; D054323:Shiga-Toxigenic Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D022641:Shiga Toxin 2; D000667:Ampicillin