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1.
BMC Genomics ; 21(1): 196, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126975

RESUMO

BACKGROUND: Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. RESULTS: Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon. CONCLUSIONS: This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.

2.
Biol Proced Online ; 21: 22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807121

RESUMO

Background: IRE1α-mediated unconventional splicing of XBP1 is emerging as a biomarker in several disease states and is indicative of activation of the unfolded protein response sensor IRE1. Splicing of XBP1 mRNA results in the translation of two distinct XBP1 protein isoforms (XBP1s and XBP1u) which, due to post-translational regulation, do not correlate with mRNA levels. As both XBP1 isoforms are implicated in pathogenic or disease progression mechanisms there is a need for a reliable, clinically applicable method to detect them. Methods: A multiplexed isoform-specific XBP1 array utilising Biochip array technology (BAT™) was assessed for specificity and suitability when using cell protein lysates. The array was applied to RIPA protein lysates from several relevant pre-clinical models with an aim to quantify XBP1 isoforms in comparison with RT-PCR or immunoblot reference methods. Results: A novel reliable, specific and sensitive XBP1 biochip was successfully utilised in pre-clinical research. Application of this biochip to detect XBP1 splicing at the protein level in relevant breast cancer models, under basal conditions as well as pharmacological inhibition and paclitaxel induction, confirmed the findings of previous studies. The biochip was also applied to non-adherent cells and used to quantify changes in the XBP1 isoforms upon activation of the NLRP3 inflammasome. Conclusions: The XBP1 biochip enables isoform specific quantification of protein level changes upon activation and inhibition of IRE1α RNase activity, using a routine clinical methodology. As such it provides a research tool and potential clinical tool with a quantified, simultaneous, rapid output that is not available from any other published method.

3.
NPJ Genom Med ; 4: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814998

RESUMO

The developmental and epileptic encephalopathies (DEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for a lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 putative transcript models. Our annotations increase the transcriptional 'footprint' of these genes by over 674 kb. Using SCN1A as a case study, due to its close phenotype/genotype correlation with Dravet syndrome, we screened 122 people with Dravet syndrome or a similar phenotype with a panel of exon sequences representing eight established genes and identified two de novo SCN1A variants that now - through improved gene annotation - are ascribed to residing among our exons. These two (from 122 screened people, 1.6%) molecular diagnoses carry significant clinical implications. Furthermore, we identified a previously classified SCN1A intronic Dravet syndrome-associated variant that now lies within a deeply conserved exon. Our findings illustrate the potential gains of thorough gene annotation in improving diagnostic yields for genetic disorders.

4.
PLoS Pathog ; 15(10): e1008003, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31581229

RESUMO

Specific Escherichia coli isolates lysogenised with prophages that express Shiga toxin (Stx) can be a threat to human health, with cattle being an important natural reservoir. In many countries the most severe pathology is associated with enterohaemorrhagic E. coli (EHEC) serogroups that express Stx subtype 2a. In the United Kingdom, phage type (PT) 21/28 O157 strains have emerged as the predominant cause of life-threatening EHEC infections and this phage type commonly encodes both Stx2a and Stx2c toxin types. PT21/28 is also epidemiologically linked to super-shedding (>103 cfu/g of faeces) which is significant for inter-animal transmission and human infection as demonstrated using modelling studies. We demonstrate that Stx2a is the main toxin produced by stx2a+/stx2c+ PT21/28 strains induced with mitomycin C and this is associated with more rapid induction of gene expression from the Stx2a-encoding prophage compared to that from the Stx2c-encoding prophage. Bacterial supernatants containing either Stx2a and/or Stx2c were demonstrated to restrict growth of bovine gastrointestinal organoids with no restriction when toxin production was not induced or prevented by mutation. Isogenic strains that differed in their capacity to produce Stx2a were selected for experimental oral colonisation of calves to assess the significance of Stx2a for both super-shedding and transmission between animals. Restoration of Stx2a expression in a PT21/28 background significantly increased animal-to-animal transmission and the number of sentinel animals that became super-shedders. We propose that while both Stx2a and Stx2c can restrict regeneration of the epithelium, it is the relatively rapid and higher levels of Stx2a induction, compared to Stx2c, that have contributed to the successful emergence of Stx2a+ E. coli isolates in cattle in the last 40 years. We propose a model in which Stx2a enhances E. coli O157 colonisation of in-contact animals by restricting regeneration and turnover of the colonised gastrointestinal epithelium.


Assuntos
Doenças dos Bovinos/transmissão , Células Epiteliais/microbiologia , Infecções por Escherichia coli/veterinária , Escherichia coli O157/efeitos dos fármacos , Íleo/microbiologia , Organoides/microbiologia , Toxina Shiga II/farmacologia , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Escherichia coli O157/isolamento & purificação , Íleo/citologia , Íleo/metabolismo , Masculino , Organoides/crescimento & desenvolvimento , Organoides/metabolismo , Virulência
5.
J Biomech Eng ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31523751

RESUMO

Knee osteoarthritis (OA) is a significant problem in the aging population, causing pain, impaired mobility, and decreased quality of life. Conservative treatment methods are necessary to reduce rapidly increasing rates of knee joint surgery. Recommended strategies include weight loss and knee bracing to unload knee joint forces. Although weight loss can be beneficial for joint unloading, knee OA patients often find it difficult to lose weight or exercise due to knee pain, and not all patients are overweight. Uni-compartment offloader braces can redistribute joint forces away from one tibiofemoral (TF) compartment, however, <5% of patients have uni-compartmental TFOA, while isolated patellofemoral or multi-compartmental OA are much more common. By absorbing body weight and assisting the knee extension moment using a spring-loaded hinge, sufficiently powerful knee-extension-assist (KEA) braces could be useful for unloading the whole knee. This paper describes the design of a spring-loaded tri-compartment unloader (TCU) knee brace intended to provide unloading in all three knee compartments while weight-bearing, measures and compares the force output of the TCU against the only published and commercially available KEA brace, and calculates the static unloading capacity of each device. The TCU and KEA braces delivered maximum assistive moments equivalent to reducing body weight by 45 and 6 lbs, respectively. The paper concludes that sufficiently powerful spring-loaded knee braces show promise in a new class of multi-compartment unloader knee orthoses, capable of providing a clinically meaningful unloading effect across all three knee compartments.

6.
Genome Res ; 29(12): 2073-2087, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31537640

RESUMO

The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present the first whole-genome PhyloCSF prediction tracks for human, mouse, chicken, fly, worm, and mosquito. We develop a workflow that uses machine learning to predict novel conserved protein-coding regions and efficiently guide their manual curation. We analyze more than 1000 high-scoring human PhyloCSF regions and confidently add 144 conserved protein-coding genes to the GENCODE gene set, as well as additional coding regions within 236 previously annotated protein-coding genes, and 169 pseudogenes, most of them disabled after primates diverged. The majority of these represent new discoveries, including 70 previously undetected protein-coding genes. The novel coding genes are additionally supported by single-nucleotide variant evidence indicative of continued purifying selection in the human lineage, coding-exon splicing evidence from new GENCODE transcripts using next-generation transcriptomic data sets, and mass spectrometry evidence of translation for several new genes. Our discoveries required simultaneous comparative annotation of other vertebrate genomes, which we show is essential to remove spurious ORFs and to distinguish coding from pseudogene regions. Our new coding regions help elucidate disease-associated regions by revealing that 118 GWAS variants previously thought to be noncoding are in fact protein altering. Altogether, our PhyloCSF data sets and algorithms will help researchers seeking to interpret these genomes, while our new annotations present exciting loci for further experimental characterization.

7.
Physiol Rep ; 7(12): e14153, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243891

RESUMO

Hemoglobin levels are believed to be regulated as per a set point model of regulation. This model of regulation, by which specific levels of a parameter are targeted and defended by physiological systems, implies a particular population correlation between the parameter and its controlling hormone. Empirical population correlations of other parameters and their controlling hormones, have denied the presence of such set point-based regulation. To assess if hemoglobin is regulated according to a set point model we performed a systematic search of PubMed/MEDLINE and Web of Science identifying relevant reports published up to November 2018. Population hemoglobin/erythropoietin level correlations were retrieved, and these empirically derived correlations were compared with the positive correlation implied by a set point model of regulation. Authors of papers containing potentially suitable data were contacted with requests for further analyses, and a meta-analysis was performed. Twelve correlations between hemoglobin and erythropoietin levels from eleven papers were analyzed. None of these correlations were significantly positive, three, restricted to the normal range of hemoglobin, were significantly negative. All but one of the other correlations showed a negative trend. New analyses of previously published data sets resulted in similar findings. In particular a new analysis of large data sets of males (n = 2417) and females (n = 2592) with normal range hemoglobin levels, revealed significantly negative correlations. A meta-analysis of our results indicated that the data overall are not consistent with a positive relationship between hemoglobin and erythropoietin (P < 0.0001). Population data indicate that individuals do not have set point levels of hemoglobin.

8.
J Agromedicine ; 24(2): 138-145, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30860962

RESUMO

Partial results of a NIOSH-funded study for "Protecting the Logging Workforce: Development of Innovative Logging Techniques for a Safer Work Environment" by a team of researchers at Oregon State University are presented that review safety in steep slope logging. Comparisons are made for hazards and exposures of "conventional" and new technologies for steep slopes. Hazards of new technologies are identified. Safety assessments are addressed for forestry sectors internationally, for the firm and for workers. Important questions of technical feasibility, economic viability and environmental performance are raised. Ongoing research on operators using tethered and untethered systems are described. Results will help inform training and selecting operators. New Best Operating Practices and safety code regulations will result from the research. New technologies will reduce worker hazards and exposures for steep slope logging.


Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Fazendeiros/estatística & dados numéricos , Agricultura Florestal/estatística & dados numéricos , Saúde do Trabalhador/normas , Acidentes de Trabalho/prevenção & controle , Agricultura Florestal/instrumentação , Agricultura Florestal/organização & administração , Humanos , Estados Unidos , Local de Trabalho
9.
Temperature (Austin) ; 5(4): 380-389, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574530

RESUMO

The physiological functions of Thyroid Stimulating Hormone (TSH) autoregulation, the ultra-short feedback loop inhibition of TSH by TSH itself, have not been determined. In this work we explored the role of TSH autoregulation in thyroid homeostasis. We synthesized the known physiology of autoregulation with theknown physiological relationships between thyroid hormones; in particular between free thyroxine and TSH. We analysed the implications of TSH autoregulation, on the generation of the TSH response to free thyroxine (the 'TSH curve'), and on the variation inthis response, which might result from variations in hypothalamopituitary or thyroid gland function. Our analysis demonstrated that, in the circumstances of inter-individual and intra-individual variations to hypothalamo-pituitary function TSH autoregulation lessens variation in the TSH curve. This in turn enhances the probability of generating and maintaining a euthyroid free thyroxine value. This contribution of TSH autoregulation to the stabilisation of thyroid physiology offers a logical explanation for the evolutionary selection of this physiological process.

10.
Acta Biomater ; 77: 85-95, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30030173

RESUMO

To decouple the effects of collagen fiber density and network mechanics on cancer cell behavior, we describe a highly tunable in vitro 3D interpenetrating network (IPN) consisting of a primary fibrillar collagen network reinforced by a secondary visible light-mediated thiol-ene poly(ethylene glycol) (PEG) network. This PEG/Collagen IPN platform is cytocompatible, inherently bioactive via native cellular adhesion sites, and mechanically tunable over several orders of magnitude-mimicking both healthy and cancerous breast tissue. Furthermore, we use the PEG/Collagen IPN platform to investigate the effect of mechanical confinement on cancer cell behavior as it is hypothesized that cells within tumors that have yet to invade into the surrounding tissue experience mechanical confinement. We find that mechanical confinement via the IPN impairs behavior characteristic of malignant cells (i.e., viability, proliferation, and cellular motility) in the triple negative breast cancer cell line MDA.MB.231, and is more effective than removal of soluble growth signals. The PEG/Collagen IPN platform is a useful tool for studying mechanotransductive signaling pathways and motivates further investigation into the role of mechanical confinement in cancer progression. STATEMENT OF SIGNIFICANCE: In this study, we have developed, optimized, and applied a novel 3D in vitro cell culture platform composed of an interpenetrating network (IPN) that is both mechanically tunable and inherently bioactive. The IPN consists of a primary fibrillar collagen type-1 network reinforced by a secondary thiol-ene poly(ethylene glycol) (PEG) network. The IPNs are formed via a novel strategy in which cell-laden collagen gels are formed first, and soluble PEG monomers are added later and crosslinked via visible light. This approach ensures that the collagen gels contain a fibrillar architecture similar to the collagen architecture present in vivo. We applied our IPN platform to study the effect of mechanical confinement on cancer cell behavior and found that it inhibits malignant-like behavior.


Assuntos
Colágeno/química , Polietilenoglicóis/química , Neoplasias de Mama Triplo Negativas/patologia , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Difusão , Matriz Extracelular/efeitos dos fármacos , Análise de Elementos Finitos , Humanos , Hidrogéis/farmacologia , Luz , Teste de Materiais , Microscopia Eletrônica de Varredura , Transdução de Sinais , Estresse Mecânico , Engenharia Tecidual , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral
11.
Physiol Rep ; 6(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29333728

RESUMO

The prevailing teaching regarding homeostasis, and in particular endocrine homeostasis, includes the fundamental concept of a "set point," which represents a target or optimum level defended by physiological control mechanisms. Analogies for the description and teaching of this concept have included thermostats and cruise controls. We previously demonstrated that such a set-point model of regulation implies that in population data of parameter set point/controlling hormone levels, correlations between the parameter and its controlling hormone must be in the direction of the response of the parameter to its controlling hormone, and that in thyroid homeostasis this relationship is not observed. In this work we similarly examined population correlations, extracted from the literature, for the parameters glucose and calcium, and their controlling hormones. We found 10 correlations. Most were highly significant (P < 0.01). All were in the direction of the response of the controlling hormone to the parameter. Therefore, none were consistent with the pattern implied by a set-point model of regulation. Instead all were consistent with an "equilibrium point" model of regulation, whereby ambient levels have no particular connotation to the individual, and result passively from the interplay of physiological processes. We conclude that glucose and calcium regulation, like thyroid regulation, are not centered on set points. This may reflect a general property of homeostasis. We provide an alternative mechanistic analogy, without a set point, for the heuristic description and teaching, of homeostasis.


Assuntos
Glicemia/metabolismo , Cálcio/sangue , Homeostase , Modelos Biológicos , População , Correlação de Dados , Feminino , Humanos , Masculino , Hormônios Tireóideos/sangue
12.
J Comorb ; 7(1): 50-63, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29090189

RESUMO

BACKGROUND: The external validity, or generalizability, of trials and guidelines has been considered poor in the context of multiple morbidity. How multiple morbidity might affect the magnitude of benefit of a given treatment, and thereby external validity, has had little study. OBJECTIVE: To provide a method of decision analysis to quantify the effects of age and comorbidity on the probability of deriving a given magnitude of treatment benefit. DESIGN: We developed a method to calculate probabilistically the effect of all of a patient's comorbidities on their underlying utility, or well-being, at a future time point. From this, we derived a distribution of possible magnitudes of treatment benefit at that future time point. We then expressed this distribution as the probability of deriving at least a given magnitude of treatment benefit. To demonstrate the applicability of this method of decision analysis, we applied it to the treatment of hypercholesterolaemia in a geriatric population of 50 individuals. We highlighted the results of four of these individuals. RESULTS: This method of analysis provided individualized quantifications of the effect of age and comorbidity on the probability of treatment benefit. The average probability of deriving a benefit, of at least 50% of the magnitude of benefit available to an individual without comorbidity, was only 0.8%. CONCLUSION: The effects of age and comorbidity on the probability of deriving significant treatment benefits can be quantified for any individual. Even without consideration of other factors affecting external validity, these effects may be sufficient to guide decision-making.

13.
J Thyroid Res ; 2017: 6917841, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28913003

RESUMO

[This corrects the article DOI: 10.1155/2016/6351473.].

15.
Genome Announc ; 5(4)2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28126943

RESUMO

The genome of Salmonella enterica subspecies enterica serovar Enteritidis phage type 8 strain EN1660, isolated from an outbreak in Thunder Bay, Canada, was sequenced to 46-fold coverage using an Illumina MiSeq with 300-bp paired-end sequencing chemistry to produce 28 contigs with an N50 value of 490,721 bp.

16.
Front Microbiol ; 7: 1930, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27965652

RESUMO

Infections caused by Shiga toxin (Stx)-producing E. coli strains constitute a health problem, as they are problematic to treat. Stx production is a key virulence factor associated with the pathogenicity of enterohaemorrhagic E. coli (EHEC) and can result in the development of haemolytic uremic syndrome in infected patients. The genes encoding Stx are located on temperate lysogenic phages integrated into the bacterial chromosome and expression of the toxin is generally coupled to phage induction through the SOS response. We aimed to find new compounds capable of blocking expression of Stx type 2 (Stx2) as this subtype of Stx is more strongly associated with human disease. High-throughput screening of a small-molecule library identified a lead compound that reduced Stx2 expression in a dose-dependent manner. We show that the optimized compound interferes with the SOS response by directly affecting the activity and oligomerization of RecA, thus limiting phage activation and Stx2 expression. Our work suggests that RecA is highly susceptible to inhibition and that targeting this protein is a viable approach to limiting production of Stx2 by EHEC. This type of approach has the potential to limit production and transfer of other phage induced and transduced determinants.

18.
J Thyroid Res ; 2016: 6351473, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27123359

RESUMO

Context. Population studies of the distribution of T4/TSH set points suggest a more complex inverse relationship between T4 and TSH than that suggested by physiological studies. The reasons for the similarities and differences between the curves describing these relationships are unresolved. Methods. We subjected the curve, derived from empiric data, describing the TSH suppression response to T4, and the more mathematically derived curve describing the T4 response to TSH, to the different possible models of population variation. The implied consequences of these in terms of generating a population distribution of T4/TSH equilibrium points (a "population curve") were generated and compared to the empiric population curve. The physiological responses to primary hypothyroidism and hyperthyroidism were incorporated into the analysis. Conclusions. Though the population curve shows a similarly inverse relationship, it is describing a different relationship than the curve describing the suppression of TSH by T4. The population curve is consistent with the physiological studies of the TSH response to T4 and implies a greater interindividual variation in the positive thyroid T4 response to TSH than in the central inhibitory TSH response to T4. The population curve in the dysthyroid states is consistent with known physiological responses to these states.

19.
Artigo em Inglês | MEDLINE | ID: mdl-26896847

RESUMO

Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org.


Assuntos
Biologia Computacional/métodos , Genoma , Genômica , Algoritmos , Animais , DNA Complementar/genética , Bases de Dados Genéticas , Evolução Molecular , Etiquetas de Sequências Expressas , Humanos , Filogenia , Controle de Qualidade , RNA não Traduzido/genética , Alinhamento de Sequência , Análise de Sequência de RNA , Software
20.
Microb Genom ; 2(9): e000084, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-28348875

RESUMO

Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a public health threat and outbreaks occur worldwide. Here, we investigate genomic differences between related STEC O157:H7 that caused two outbreaks, eight weeks apart, at the same restaurant. Short-read genome sequencing divided the outbreak strains into two sub-clusters separated by only three single-nucleotide polymorphisms in the core genome while traditional typing identified them as separate phage types, PT8 and PT54. Isolates did not cluster with local strains but with those associated with foreign travel to the Middle East/North Africa. Combined long-read sequencing approaches and optical mapping revealed that the two outbreak strains had undergone significant microevolution in the accessory genome with prophage gain, loss and recombination. In addition, the PT54 sub-type had acquired a 240 kbp multi-drug resistance (MDR) IncHI2 plasmid responsible for the phage type switch. A PT54 isolate had a general fitness advantage over a PT8 isolate in rich medium, including an increased capacity to use specific amino acids and dipeptides as a nitrogen source. The second outbreak was considerably larger and there were multiple secondary cases indicative of effective human-to-human transmission. We speculate that MDR plasmid acquisition and prophage changes have adapted the PT54 strain for human infection and transmission. Our study shows the added insights provided by combining whole-genome sequencing approaches for outbreak investigations.


Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli O157/genética , Genoma Bacteriano/genética , África do Norte , Surtos de Doenças , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/transmissão , Evolução Molecular , Humanos , Oriente Médio , Plasmídeos/genética , Prófagos/genética
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