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Genomic diversity of EPEC associated with clinical presentations of differing severity.

ABSTRACT: Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature. Comparative genomics of 70 total EPEC from lethal (LI), non-lethal symptomatic (NSI) or asymptomatic (AI) cases of diarrhoeal illness in children enrolled in the Global Enteric Multicenter Study was used to investigate the genomic differences in EPEC isolates obtained from individuals with various clinical outcomes. A comparison of the genomes of isolates from different clinical outcomes identified genes that were significantly more prevalent in EPEC isolates of symptomatic and lethal outcomes than in EPEC isolates of asymptomatic outcomes. These EPEC isolates exhibited previously unappreciated phylogenomic diversity and combinations of virulence factors. These comparative results highlight the diversity of the pathogen, as well as the complexity of the EPEC virulence factor repertoire.

SUBMITTER: Hazen TH

PROVIDER: S-EPMC5067155 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Genomic diversity of EPEC associated with clinical presentations of differing severity.

Hazen Tracy H TH Donnenberg Michael S MS Panchalingam Sandra S Antonio Martin M Hossain Anowar A Mandomando Inacio I Ochieng John Benjamin JB Ramamurthy Thandavarayan T Tamboura Boubou B Qureshi Shahida S Quadri Farheen F Zaidi Anita A Kotloff Karen L KL Levine Myron M MM Barry Eileen M EM Kaper James B JB Rasko David A DA Nataro James P JP

Nature microbiology 20160118

Enteropathogenic Escherichia coli (EPEC) are diarrhoeagenic E. coli, and are a significant cause of gastrointestinal illness among young children in developing countries. Typical EPEC are identified by the presence of the bundle-forming pilus encoded by a virulence plasmid, which has been linked to an increased severity of illness, while atypical EPEC lack this feature. Comparative genomics of 70 total EPEC from lethal (LI), non-lethal symptomatic (NSI) or asymptomatic (AI) cases of diarrhoeal i ...[more]

PMID: 27571975

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Project description:The clinical presentations and outcomes of SARS-CoV-2 infection are highly variable, ranging from asymptomatic infections to severe conditions, and the underlying mechanisms remain largely unknown. In this study, we performed the single-cell RNA sequencing to examine the profiles of the peripheral blood mononuclear cells (PBMCs) from the healthy controls (HC), asymptomatic individuals (AS) and symptomatic COVID-19 patients (SM) with various clinical features and disease severity. We first identified nine major cell types, including T cells, B cells, monocytes, natural killer (NK) cells, dendritic cells (DC), platelets, neutrophils, plasma cells and stem cells from a total of 119,799 single cells captured and filtered for the final analysis, and then divided these cell types into separate cell clusters and sub-clusters, respectively. We revealed that SARS-CoV-2 infection resulted in profound alternations in various cellular compartments and identified a number of distinct immune cell subsets that were associated with various clinical presentations, disease severity and viral persistence of COVID-19. (NCAM1+CD160+) NK cells increased significantly in AS and SM individuals compared with the HC. SM patients showed a significant increase in (LAG3+CD160+CD8+) NKT cells and a decrease in (CD4-CD8-) double negative T cells compared with the AS subjects. (CD68-CSF1R-IL1BhiCD14+) classical monocytes were significantly higher in patients with severe disease (SD) than the patients with moderate disease (MD). (CD68-CSF1R-IL1BhiCD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were positively and negatively correlated with the age-related disease severity of COVID-19 patients, respectively. Increases in (CD33-HLA-DMA-CD14+) classical monocytes and (CLEC10A-S100A9lo)pDC were associated with long-term nucleic acid test positive (LTNP) patients compared with the short-term nucleic acid test positive (STNP) individuals. Increases in (LAG3+CD160+CD8+) NKTcells and (FOXP3+IL2RA+IL7R+CD4+) Treg cells were observed in a patient lacking B cells and plasma cells. Dramatic increases in neutrophils, (CD33-HLA-DMA-CD14+) classical monocytes, and (CD68-CSF1R-IL1BhiCD14+) classical monocytes were detected at a later stage of a fatal patient. Our findings may enhance our understanding of the immune cell alternations involved in the pathogenesis of COVID-19 and the protective immune responses against SARS-CoV-2 infection.

Project description:BackgroundBurden estimates of medically and nonmedically attended influenza-associated illness across syndromes and levels of severity are lacking.MethodsWe estimated the national burden of medically and nonmedically attended influenza-associated illness among individuals with different clinical presentations (all-respiratory, all-circulatory, and nonrespiratory/noncirculatory) and levels of severity (mild, fatal, and severe, nonfatal) using a combination of case-based (from laboratory-confirmed influenza surveillance) and ecological studies, as well as data from healthcare utilization surveys in South Africa during 2013-2015. In addition, we compared estimates of medically attended influenza-associated respiratory illness, obtained from case-based and ecological studies. Rates were reported per 100 000 individuals in the population.ResultsThe estimated mean annual number of influenza-associated illness episodes was 10 737 847 (19.8% of 54 096 705 inhabitants). Of these episodes, 10 598 138 (98.7%) were mild, 128 173 (1.2%) were severe, nonfatal, and 11 536 (0.1%) were fatal. There were 2 718 140 (25.6%) mild, 56 226 (43.9%) severe, nonfatal, and 4945 (42.8%) medically attended should be after fatal episodes. Influenza-associated respiratory illness accounted for 99.2% (10 576 146) of any mild, 65.5% (83 941) of any severe, nonfatal, and 33.7% (3893) of any fatal illnesses. Ecological and case-based estimates of medically attended, influenza-associated, respiratory mild (rates: ecological, 1778.8, vs case-based, 1703.3; difference, 4.4%), severe, nonfatal (rates: ecological, 88.6, vs case-based, 75.3; difference, 15.0%), and fatal (rates: ecological, 3.8, vs case-based, 3.5; difference, 8.4%) illnesses were similar.ConclusionsThere was a substantial burden of influenza-associated symptomatic illness, including severe, nonfatal and fatal illnesses, and a large proportion was nonmedically attended. Estimates, including only influenza-associated respiratory illness, substantially underestimated influenza-associated, severe, nonfatal and fatal illnesses. Ecological and case-based estimates were found to be similar for the compared categories.

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Genomic diversity of EPEC associated with clinical presentations of differing severity.

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Genomic diversity of EPEC associated with clinical presentations of differing severity.

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