Showing papers by "Alison D. O'Brien published in 2003"

Shiga Toxin–Producing Escherichia coli in Montana: Bacterial Genotypes and Clinical Profiles

Abstract: The diseases and virulence genes associated with Shiga toxin-producing Escherichia coli (STEC) are characterized incompletely. We analyzed, by polymerase chain reaction, 82 STEC isolates collected prospectively in Montana and profiled associated illnesses by patient chart review. All E. coli O157:H7 contained stx2-group genes, as well as eae, iha, espA, and ehxA; 84% contained stx1. Non-O157:H7 STEC less frequently contained stx1 (P=.046), stx2 (P<.001), iha (P<.001), eae, and espA (P=.039 for both), were isolated less often from patients treated in emergency departments (P=.022), and tended to be associated less frequently with bloody diarrhea (P=.061). There were no significant associations between stx genotype and bloody diarrhea, but isolates containing stx2c or stx(2d-activatable) were recovered more often from patients who underwent diagnostic or therapeutic procedures (P=.033). Non-O157:H7 STEC are more heterogeneous and cause bloody diarrhea less frequently than do E. coli O157:H7. Bloody diarrhea cannot be attributed simply to the stx genotype of the infecting organism.

Comparative pathogenicity of Escherichia coli O157 and intimin-negative non-O157 Shiga toxin-producing E coli strains in neonatal pigs.

Abstract: We compared the pathogenicity of intimin-negative non-O157:H7 Shiga toxin (Stx)-producing Escherichia coli (STEC) O91:H21 and O104:H21 strains with the pathogenicity of intimin-positive O157:H7 and O157:H strains in neonatal pigs. We also examined the role of Stx2d-activatable genes and the large hemolysinencoding plasmid of O91:H21 strain B2F1 in the pathogenesis of STEC disease in pigs. We found that all E. coli strains that made wild-type levels of Stx caused systemic illness and histological lesions in the brain and intestinal crypts, whereas none of the control Stx-negative E. coli strains evoked comparable central nervous system signs or intestinal lesions. By contrast, the absence of intimin, hemolysin, or motility had little impact on the overall pathogenesis of systemic disease during STEC infection. The most striking differences between pigs inoculated with non-O157 STEC strains and pigs inoculated with O157 STEC strains were the absence of attaching and effacing intestinal lesions in pigs inoculated with non-O157:H7 strains and the apparent association between the level of Stx2d-activatable toxin produced by an STEC strain and the severity of lesions. Serotype O157:H7 Shiga toxin (Stx)-producing Escherichia coli (STEC) strains cause the majority of sporadic and multiperson outbreaks of bloody diarrhea in the United States (15). However, non-O157 STEC strains were the source of three such outbreaks of bloody diarrhea (1) and an apparent cluster of three cases of hemolytic-uremic syndrome (HUS) (5, 26) and may be responsible for 20% (2) or even 50% (13) of all STEC infections. Up to 10% of patients with hemorrhagic colitis due to infection with an O157 strain develop HUS, a sequela that includes serious kidney damage. The risk of HUS for patients infected with non-O157 STEC is not as clear, but it could be as high as that for patients infected with O157 strains (29). STEC can be grouped by the array of potential virulence

Statement on the consideration of biodefence and biosecurity.

Abstract: As discussed in a Commentary by Tony Fauci on page 787, the threat of bioterrorism requires active consideration by scientists. On 9 January 2003, the US National Academy of Sciences held a discussion meeting on the balance between scientific openness and security (see Nature 421, 197; 2003). The next day, a group of editors* met to discuss the issues with specific reference to the scientific publication process. The following statement has emerged from that meeting. The statement was conceived in a US context, but the principles discussed will be considered and followed through by Nature and its related journals in their international arenas.

Uncensored exchange of scientific results.

Abstract: T he process of scientific publication, through which new findings are reviewed for quality and then presented to the rest of the scientific community and the public, is a vital element in our national life. New discoveries reported in research papers have helped improve the human condition in myriad ways: protecting public health, multiplying agricultural yields, fostering technological development and economic growth, and enhancing global stability and security. But new science, as we know, may sometimes have costs as well as benefits. The prospect that weapons of mass destruction might find their way into the hands of terrorists did not suddenly appear on September 11, 2001. A policy focus on nuclear proliferation, no stranger to the physics community, has been with us for many years. But the events of September 11 brought a new understanding of the urgency of dealing with terrorism. And the subsequent harmful use of infectious agents brought a new set of issues to the life sciences. As a result, questions have been asked by the scientists themselves and by some political leaders about the possibility that new information published in research journals might give aid to those with malevolent ends. Journals that dealt especially with microbiology, infectious agents, public health, and plant and agricultural systems faced these issues earlier than some others, and have attempted to deal with them. The American Society for Microbiology (ASM), in particular, urged the National Academy of Sciences to take an active role in organizing a meeting of publishers, scientists, security experts, and government officials to explore the issues and discuss what steps might be taken to resolve them. In a one-day workshop at the Academy in Washington, DC, cohosted by the Center for Strategic and International Studies on January 9, 2003, an open forum was held for that purpose. A day later, a group of journal editors, augmented by scientist-authors, government officials, and others, held a separate meeting designed to explore possible approaches. What follows reflects some outcomes of that preliminary discussion. Fundamental is a view, shared by nearly all, that there is information that, although we cannot now capture it with lists or definitions, presents enough risk of use by terrorists that it should not be published. How and by what processes it might be identified will continue to challenge us, because, as all present acknowledged, it is also true that open publication brings benefits not only to public health but also to efforts to combat terrorism.

Shiga Toxin-Producing Escherichia coli-Associated Kidney Failure in a 40-Year-Old Patient and Late Diagnosis by Novel Bacteriologic and Toxin Detection Methods

Abstract: Infection with Shiga toxin-producing Escherichia coli (STEC) is the most common cause of kidney failure in children. High morbidity is also associated with infections in the elderly. We describe STEC-associated kidney failure in a 40-year-old patient, including the methods used to identify STEC a month after disease onset.

Plant and Bacterial Toxins as RNA N-Glycosidases

Abstract: Along with identification of the enzymatic function of ribosome-inactivating proteins (RIPs) came the recognition that certain bacterial toxins, called Shiga toxins (Stxs), fit into the category of plant proteins. We now know that these plant and bacterial poisons have the broader specificity of polynucleotide:adenosine glycosidases, at least in vitro. This chapter refers to the enzymes interchangeably as RIPs or RNA N-glycosidases. Recently, additional enzymatic activities have been attributed to the RIPs. However, when four different RIPs were highly purified, the only enzymatic activity they retained was the capacity to remove adenine from rRNA or DNA. This observation indicates that the RIPs, originally defined as RNA N-glycosidases, are actually polynucleotide:adenosine glycosidases, at least in vitro. One unusual feature of the RIPs is that, although they share the same enzymatic activity and their preferred target is intact mammalian ribosomes, they are not equally active on target ribosomes in vitro. There appear to be at least two explanations for this phenomenon. One reason that some RNA N-glycosidases do not appear to be as active as others in cell-free assays is that they require cofactors such as ATP. The second reason that some RIPs have varying specificities is that they appear to interact with ribosomal proteins. Consistent with a protective function for the plant RNA N-glycosidases is that the RIPs are both lethal and often stored in large quantities.