bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taxonomy Meets Public Health: The Case of Shiga Toxin-Producing
Escherichia coli
Authors: Scheutz Flemming 
Published: October 2014

ABSTRACT

To help assess the clinical and public health risks associated with different Shiga toxin-producing
Escherichia coli
(STEC) strains, an empirical classification scheme was used to classify STEC into five “seropathotypes” (seropathotype A [high risk] to seropathotypes D and E [minimal risk]). This definition is of considerable value in cases of human infection but is also problematic because not all STEC infections are fully characterized and coupled to reliable clinical information. Outbreaks with emerging hybrid strains continuously challenge our understanding of virulence potential and may result in incorrect classification of specific pathotypes; an example is the hybrid strain that caused the 2011 outbreak in Germany, STEC/EAggEC O104:H4, which may deserve an alternative seropathotype designation. The integration of mobile virulence factors in the stepwise and parallel evolution of pathogenic lineages of STEC collides with the requirements of a good taxonomy, which separates elements of each group into subgroups that are mutually exclusive, unambiguous, and, together, include all possibilities. The concept of (sero)-pathotypes is therefore challenged, and the need to identify factors of STEC that absolutely predict the potential to cause human disease is obvious. Because the definition of hemolytic-uremic syndrome (HUS) is distinct, a basic and primary definition of HUS-associated
E. coli
(HUSEC) for first-line public health action is proposed:
stx2
in a background of an
eae-
or
aggR
-positive
E. coli
followed by a second-line subtyping of
stx
genes that refines the definition of HUSEC to include only
stx2a
and
stx2d
. All other STEC strains are considered “low-risk” STEC.
EHEC Genomics: Past, Present, and Future
Authors: Sadiq Shah M. , Hazen Tracy H. , Rasko David A. , Eppinger Mark 
Published: October 2014

ABSTRACT

This article examines the role of genomics in the understanding and identification of O157:H7 enterohemorrhagic
Escherichia coli
(EHEC). We highlight the development of novel molecular typing systems that are based on the genomic sequence that has been generated for this pathotype. The genomic comparisons of EHEC to other
E. coli
strains highlight the close relatedness of the O157 and O55 isolates and also identify other non-O157 clades of isolates that appear to have a different genomic history. Analysis within the EHEC isolates must be completed on a fine scale using whole-genome sequence-based approaches to assess both the conserved and lateral acquired gene content. The plethora of genomic data for EHEC isolates has provided the ability to examine this pathotype in detail, which has provided opportunities for novel surveillance, detection, and diagnostics.
Shiga Toxin (Stx) Classification, Structure, and Function
Authors: Melton-Celsa Angela R. 
Published: October 2014

ABSTRACT

Shiga toxin (Stx) is one of the most potent bacterial toxins known. Stx is found in
Shigella dysenteriae
1 and in some serogroups of
Escherichia coli
(called Stx1 in
E. coli
). In addition to or instead of Stx1, some
E. coli
strains produce a second type of Stx, Stx2, that has the same mode of action as Stx/Stx1 but is antigenically distinct. Because subtypes of each toxin have been identified, the prototype toxin for each group is now designated Stx1a or Stx2a. The Stxs consist of two major subunits, an A subunit that joins noncovalently to a pentamer of five identical B subunits. The A subunit of the toxin injures the eukaryotic ribosome and halts protein synthesis in target cells. The function of the B pentamer is to bind to the cellular receptor, globotriaosylceramide, Gb3, found primarily on endothelial cells. The Stxs traffic in a retrograde manner within the cell, such that the A subunit of the toxin reaches the cytosol only after the toxin moves from the endosome to the Golgi and then to the endoplasmic reticulum. In humans infected with Stx-producing
E. coli
, the most serious manifestation of the disease, hemolytic-uremic syndrome, is more often associated with strains that produce Stx2a rather than Stx1a, and that relative toxicity is replicated in mice and baboons. Stx1a and Stx2a also exhibit differences in cytotoxicity to various cell types, bind dissimilarly to receptor analogs or mimics, induce differential chemokine responses, and have several distinctive structural characteristics.
Animal Reservoirs of Shiga Toxin-ProducingEscherichia coli
Authors: Persad Anil K. , LeJeune Jefrey T. 
Published: October 2014

ABSTRACTShiga toxin-producingEscherichia coli(STEC) strains have been detected in a wide diversity of mammals, birds, fish, and several insects. Carriage by most animals is asymptomatic, thus allowing for dissemination of the bacterium in the environment without detection. Replication of the organism may occur in the gastrointestinal tract of some animals, notably ruminants. Carriage may also be passive or transient, without significant amplification of bacterial numbers while in the animal host. Animals may be classified as reservoir species, spillover hosts, or dead-end hosts. This classification is based on the animal's ability to (i) transmit STEC to other animal species and (ii) maintain STEC infection in the absence of continuous exposure. Animal reservoirs are able to maintain STEC infections in the absence of continuous STEC exposure and transmit infection to other species. Spillover hosts, although capable of transmitting STEC to other animals, are unable to maintain infection in the absence of repeated exposure. The large diversity of reservoir and spillover host species and the survival of the organism in environmental niches result in complex pathways of transmission that are difficult to interrupt.
The Molecular Genetics of Mycolic Acid Biosynthesis
Authors: PaweŁczyk Jakub , Kremer Laurent 
Published: October 2014

ABSTRACT

Mycolic acids are major and specific long-chain fatty acids that represent essential components of the
Mycobacterium tuberculosis
cell envelope. They play a crucial role in the cell wall architecture and impermeability, hence the natural resistance of mycobacteria to most antibiotics, and represent key factors in mycobacterial virulence. Biosynthesis of mycolic acid precursors requires two types of fatty acid synthases (FASs), the eukaryotic-like multifunctional enzyme FAS I and the acyl carrier protein (ACP)–dependent FAS II systems, which consists of a series of discrete mono-functional proteins, each catalyzing one reaction in the pathway. Unlike FAS II synthases of other bacteria, the mycobacterial FAS II is incapable of
de novo
fatty acid synthesis from acetyl-coenzyme A, but instead elongates medium-chain-length fatty acids previously synthesized by FAS I, leading to meromycolic acids. In addition, mycolic acid subspecies with defined biological properties can be distinguished according to the chemical modifications decorating the meromycolate. Nearly all the genetic components involved in both elongation and functionalization of the meromycolic acid have been identified and are generally clustered in distinct transcriptional units. A large body of information has been generated on the enzymology of the mycolic acid biosynthetic pathway and on their genetic and biochemical/structural characterization as targets of several antitubercular drugs. This chapter is a comprehensive overview of mycolic acid structure, function, and biosynthesis. Special emphasis is given to recent work addressing the regulation of mycolic acid biosynthesis, adding new insights to our understanding of how pathogenic mycobacteria adapt their cell wall composition in response to environmental changes.
Evasion of Innate and Adaptive Immunity byMycobacterium tuberculosis
Authors: Goldberg Michael F. , Saini Neeraj K. , Porcelli Steven A. 
Published: October 2014

ABSTRACTThrough thousands of years of reciprocal coevolution,Mycobacterium tuberculosishas become one of humanity's most successful pathogens, acquiring the ability to establish latent or progressive infection and persist even in the presence of a fully functioning immune system. The ability ofM. tuberculosisto avoid immune-mediated clearance is likely to reflect a highly evolved and coordinated program of immune evasion strategies that interfere with both innate and adaptive immunity. These include the manipulation of their phagosomal environment within host macrophages, the selective avoidance or engagement of pattern recognition receptors, modulation of host cytokine production, and the manipulation of antigen presentation to prevent or alter the quality of T-cell responses. In this article we review an extensive array of published studies that have begun to unravel the sophisticated program of specific mechanisms that enableM. tuberculosisand other pathogenic mycobacteria to persist and replicate in the face of considerable immunological pressure from their hosts. Unraveling the mechanisms by whichM. tuberculosisevades or modulates host immune function is likely to be of major importance for the development of more effective new vaccines and targeted immunotherapy against tuberculosis.
Metallobiology of Tuberculosis
Authors: Marcela Rodriguez G. , Neyrolles Olivier 
Published: October 2014

ABSTRACT

Transition metals are essential constituents of all living organisms, playing crucial structural and catalytic parts in many enzymes and transcription factors. However, transition metals can also be toxic when present in excess. Their uptake and efflux rates must therefore be carefully controlled by biological systems. In this chapter, we summarize the current knowledge about uptake and efflux systems in
Mycobacterium tuberculosis
for mainly three of these metals, namely iron, zinc, and copper. We also propose questions for future research in the field of metallobiology of host-pathogen interactions in tuberculosis.
Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria
Authors: Cook Gregory M. , Hards Kiel , Vilchèze Catherine , Hartman Travis , Berney Michael 
Published: October 2014

ABSTRACT

Mycobacteria inhabit a wide range of intracellular and extracellular environments. Many of these environments are highly dynamic, and therefore mycobacteria are faced with the constant challenge of redirecting their metabolic activity to be commensurate with either replicative growth or a nonreplicative quiescence. A fundamental feature in this adaptation is the ability of mycobacteria to respire, regenerate reducing equivalents, and generate ATP via oxidative phosphorylation. Mycobacteria harbor multiple primary dehydrogenases to fuel the electron transport chain, and two terminal respiratory oxidases, an
aa
3
-type cytochrome
c
oxidase and a cytochrome
bd
-type menaquinol oxidase, are present for dioxygen reduction coupled to the generation of a proton motive force (PMF). Hypoxia leads to the downregulation of key respiratory complexes, but the molecular mechanisms regulating this expression are unknown. Despite being obligate aerobes, mycobacteria have the ability to metabolize in the absence of oxygen, and a number of reductases are present to facilitate the turnover of reducing equivalents under these conditions (e.g., nitrate reductase, succinate dehydrogenase/fumarate reductase). Hydrogenases and ferredoxins are also present in the genomes of mycobacteria, suggesting the ability of these bacteria to adapt to an anaerobic type of metabolism in the absence of oxygen. ATP synthesis by the membrane-bound F
1
F
0
-ATP synthase is essential for growing and nongrowing mycobacteria, and the enzyme is able to function over a wide range of PMF values (aerobic to hypoxic). The discovery of lead compounds that target respiration and oxidative phosphorylation in
Mycobacterium tuberculosis
highlights the importance of this area for the generation of new frontline drugs to combat tuberculosis.
Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids
Authors: Daffé Mamadou , Crick Dean C. , Jackson Mary 
Published: October 2014

ABSTRACT

This article summarizes what is currently known of the structures, physiological roles, involvement in pathogenicity, and biogenesis of a variety of noncovalently bound cell envelope lipids and glycoconjugates of
Mycobacterium tuberculosis
and other
Mycobacterium
species. Topics addressed in this article include phospholipids; phosphatidylinositol mannosides; triglycerides; isoprenoids and related compounds (polyprenyl phosphate, menaquinones, carotenoids, noncarotenoid cyclic isoprenoids); acyltrehaloses (lipooligosaccharides, trehalose mono- and di-mycolates, sulfolipids, di- and poly-acyltrehaloses); mannosyl-beta-1-phosphomycoketides; glycopeptidolipids; phthiocerol dimycocerosates, para-hydroxybenzoic acids, and phenolic glycolipids; mycobactins; mycolactones; and capsular polysaccharides.
Genetics of Peptidoglycan Biosynthesis
Authors: Pavelka Jr. Martin S. , Mahapatra Sebabrata , Crick Dean C. 
Published: October 2014

ABSTRACT

The complex cell envelope is a hallmark of mycobacteria and is anchored by the peptidoglycan layer, which is similar to that of
Escherichia coli
and a number of other bacteria but with modifications to the monomeric units and other structural complexities that are likely related to a role for the peptidoglycan in stabilizing the mycolyl-arabinogalactan-peptidoglycan complex (MAPc). In this article, we will review the genetics of several aspects of peptidoglycan biosynthesis in mycobacteria, including the production of monomeric precursors in the cytoplasm, assembly of the monomers into the mature wall, cell wall turnover, and cell division. Finally, we will touch upon the resistance of mycobacteria to β-lactam antibiotics, an important class of drugs that, until recently, have not been extensively exploited as potential antimycobacterial agents. We will also note areas of research where there are still unanswered questions.
Virulence Plasmids of Nonsporulating Gram-Positive Pathogens
Authors: Van Tyne Daria , Gilmore Michael S. 
Published: October 2014

ABSTRACTGram-positive bacteria are leading causes of many types of human infection, including pneumonia, skin and nasopharyngeal infections, as well as urinary tract and surgical wound infections among hospitalized patients. These infections have become particularly problematic because many of the species causing them have become highly resistant to antibiotics. The role of mobile genetic elements, such as plasmids, in the dissemination of antibiotic resistance among Gram-positive bacteria has been well studied; less well understood is the role of mobile elements in the evolution and spread of virulence traits among these pathogens. While these organisms are leading agents of infection, they are also prominent members of the human commensal ecology. It appears that these bacteria are able to take advantage of the intimate association between host and commensal organism, via virulence traits that exacerbate infection and cause disease. However, evolution into an obligate pathogen has not occurred, presumably because it would lead to rejection of pathogenic organisms from the host ecology. Instead, in organisms that exist as both commensal and pathogen, selection has favored the development of mechanisms for variability. As a result, many virulence traits are localized on mobile genetic elements, such as virulence plasmids and pathogenicity islands. Virulence traits may occur within a minority of isolates of a given species, but these minority populations have nonetheless emerged as a leading problem in infectious disease. This chapter reviews virulence plasmids in nonsporulating Gram-positive bacteria and examines their contribution to disease pathogenesis.
Plasmids as Tools for Containment
Authors: GarcíA José L. , Díaz Eduardo 
Published: October 2014

ABSTRACT
Active containment systems are a major tool for reducing the uncertainty associated with the introduction of monocultures, genetically engineered or not, into target habitats for a large number of biotechnological applications (e.g., bioremediation, bioleaching, biopesticides, biofuels, biotransformations, live vaccines, etc.). While biological containment reduces the survival of the introduced organism outside the target habitat and/or upon completion of the projected task, gene containment strategies reduce the lateral spread of the key genetic determinants to indigenous microorganisms. In fundamental research, suicide circuits become relevant tools to address the role of gene transfer, mainly plasmid transfer, in evolution and how this transfer contributes to genome plasticity and to the rapid adaptation of microbial communities to environmental changes. Many lethal functions and regulatory circuits have been used and combined to design efficient containment systems. As many new genomes are being sequenced, novel lethal genes and regulatory elements are available, e.g., new toxin-antitoxin modules, and they could be used to increase further the current containment efficiencies and to expand containment to other organisms. Although the current containment systems can increase the predictability of genetically modified organisms in the environment, containment will never be absolute, due to the existence of mutations that lead to the appearance of surviving subpopulations. In this sense, orthogonal systems (xenobiology) appear to be the solution for setting a functional genetic firewall that will allow absolute containment of recombinant organisms.
Spore Resistance Properties
Authors: Setlow Peter 
Published: October 2014

ABSTRACT

Spores of various
Bacillus
and
Clostridium
species are among the most resistant life forms known. Since the spores of some species are causative agents of much food spoilage, food poisoning, and human disease, and the spores of
Bacillus anthracis
are a major bioweapon, there is much interest in the mechanisms of spore resistance and how these spores can be killed. This article will discuss the factors involved in spore resistance to agents such as wet and dry heat, desiccation, UV and γ-radiation, enzymes that hydrolyze bacterial cell walls, and a variety of toxic chemicals, including genotoxic agents, oxidizing agents, aldehydes, acid, and alkali. These resistance factors include the outer layers of the spore, such as the thick proteinaceous coat that detoxifies reactive chemicals; the relatively impermeable inner spore membrane that restricts access of toxic chemicals to the spore core containing the spore's DNA and most enzymes; the low water content and high level of dipicolinic acid in the spore core that protect core macromolecules from the effects of heat and desiccation; the saturation of spore DNA with a novel group of proteins that protect the DNA against heat, genotoxic chemicals, and radiation; and the repair of radiation damage to DNA when spores germinate and return to life. Despite their extreme resistance, spores can be killed, including by damage to DNA, crucial spore proteins, the spore's inner membrane, and one or more components of the spore germination apparatus.
Physiology and Sporulation in
Clostridium
Authors: Dürre Peter 
Published: October 2014

ABSTRACT

Clostridia are Gram-positive, anaerobic, endospore-forming bacteria, incapable of dissimilatory sulfate reduction. Comprising approximately 180 species, the genus
Clostridium
is one of the largest bacterial genera. Physiology is mostly devoted to acid production. Numerous pathways are known, such as the homoacetate fermentation by acetogens, the propionate fermentation by
Clostridium propionicum
, and the butyrate/butanol fermentation by
C. acetobutylicum
, a well-known solvent producer. Clostridia degrade sugars, alcohols, amino acids, purines, pyrimidines, and polymers such as starch and cellulose. Energy conservation can be performed by substrate-level phosphorylation as well as by the generation of ion gradients. Endospore formation resembles the mechanism elucidated in
Bacillus
. Morphology, contents, and properties of spores are very similar to bacilli endospores. Sporulating clostridia usually form swollen mother cells and accumulate the storage substance granulose. However, clostridial sporulation differs by not employing the so-called phosphorelay. Initiation starts by direct phosphorylation of the master regulator Spo0A. The cascade of sporulation-specific sigma factors is again identical to what is known from
Bacillus
. The onset of sporulation is coupled in some species to either solvent (acetone, butanol) or toxin (e.g.,
C. perfringens
enterotoxin) formation. The germination of spores is often induced by various amino acids, often in combination with phosphate and sodium ions. In medical applications,
C. butyricum
spores are used as a
C. difficile
prophylaxis and as treatment against diarrhea. Recombinant spores are currently under investigation and testing as antitumor agents, because they germinate only in hypoxic tissues (i.e., tumor tissue), allowing precise targeting and direct killing of tumor cells.
Point-of-care assessment of platelet reactivity in the emergency department may facilitate rapid rule-out of acute coronary syndromes: a prospective cohort pilot feasibility study
Authors: Darling Chad E , Sala Mercado Javier A , Quiroga-Castro Walter , Tecco Gabriel F , Zelaya Felix R , Conci Eduardo C , Sala Jose P , Smith Craig S , Michelson Alan D , Whittaker Peter , Welch Robert D , Przyklenk Karin 
Published: October 2014

ObjectiveAccurate, efficient and cost-effective disposition of patients presenting to emergency departments (EDs) with symptoms suggestive of acute coronary syndromes (ACS) is a growing priority. Platelet activation is an early feature in the pathogenesis of ACS; thus, we sought to obtain an insight into whether point-of-care testing of platelet function: (1) may assist in the rule-out of ACS; (2) may provide additional predictive value in identifying patients with non-cardiac symptoms versus ACS-positive patients and (3) is logistically feasible in the ED.DesignProspective cohort feasibility study.SettingTwo urban tertiary care sites, one located in the USA and the second in Argentina.Participants509 adult patients presenting with symptoms of ACS.Main outcome measuresPlatelet reactivity was quantified using the Platelet Function Analyzer-100, with closure time (seconds required for blood, aspirated under high shear, to occlude a 150 µm aperture) serving as the primary endpoint. Closure times were categorised as ‘normal’ or ‘prolonged’, defined objectively as the 90th centile of the distribution for all participants enrolled in the study. Diagnosis of ACS was made using the standard criteria. The use of antiplatelet agents was not an exclusion criterion.ResultsClosure times for the study population ranged from 47 to 300 s, with a 90th centile value of 138 s. The proportion of patients with closure times ≥138 s was significantly higher in patients with non-cardiac symptoms (41/330; 12.4%) versus the ACS-positive cohort (2/105 (1.9%); p=0.0006). The specificity of ‘prolonged’ closure times (≥138 s) for a diagnosis of non-cardiac symptoms was 98.1%, with a positive predictive value of 95.4%. Multivariate analysis revealed that the closure time provided incremental, independent predictive value in the rule-out of ACS.ConclusionsPoint-of-care assessment of platelet reactivity is feasible in the ED and may facilitate the rapid rule-out of ACS in patients with prolonged closure times.