Utilisateur:JackBortone/Research/Topics/STCOV19

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Abstract

Recent work has identified the bacterial organism Escherichia coli O157:H7 EDL933 as a emerging food-borne pathogen in Central China. [1] Our experimental report confirms a novel E. coli O157:H7 variant isolated from the reference QHD43416.1 proteome in the pathology of COVID19 phenotype.

Method

MSA template setup

To identify conserved structural domains from E. coli ancestor O157:H7 in the QHD43416.1 proteome, we designed a sequential workflow based on initial MSA alignment generated with webPRANK

Proteome database parameters

hhsearch command line : 

% hhsearch -cpu 8 -i ../results/full.a3m -d /cluster/toolkit/production/databases/hh-suite/pfama/pfama -d /cluster/toolkit/production/databases/hh-suite/mmcif70/pdb70 -d /cluster/toolkit/production/databases/hh-suite/Proteomes/Escherichia_coli_K12/Escherichia_coli_K12 -o ../results/9699200_1.hhr -oa3m ../results/9699200_1.a3m -p 50 -Z 250 -loc -z 1 -b 1 -B 250 -ssm 2 -sc 1 -seq 1 -dbstrlen 10000 -norealign -maxres 32000 -contxt /cluster/toolkit/production/bioprogs/tools/hh-suite-build-new/data/context_data.crf

HHpred sequence prediction

HHpred is a highly sensitive remote protein homology detection tool preferred over PSI-BLAST since it is optimized for medium-size HMM based identification of translocated proteins with a PH-like (transmembrane) domain. [2]

Results

Still waiting for my DOI.... :)

Discussion

Genetic evidences of translocated E. Coli remote homologs in the SARS-CoV-2 glycoprotein

The remote detection of ECF sigma factors from E.coli proteome using HMM comparison (HHpred) of target viral protein with MSA template (PRANK) positively identified significant hits (98) in pfam and pdb (Uniprot) databases associated to this E. coli specific RNA polymerase. In addition another HHpred query identified the Tir N-terminal domain (Organism: E. coli) with higher probability (100%) than coronavirus spike glycoprotein S1 (39.59%).

Sensor protein CpxA

The serotonin sensor (CpxA) is a E. coli O157:H7 specific gene identified in the reference proteome suggesting a significant risk factor for people with lower serotonin/dopamine levels. [3]

Supplemental data

Motif scan

1. Shiga/ricin ribosomal inactivating toxins active site signature : 

VTVTAEALRFRQIQRGF

References

  1. https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-019-2177-1

    [Paper6]

    O-serogroups, virulence genes, antimicrobial susceptibility, and MLST genotypes of Shiga toxin-producing Escherichia coli from swine and cattle in Central China

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091641/

    [Paper9]

    Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains

  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893822/

    [Paper12]

    Protracted effects of chronic stress on serotonin dependent thermoregulation

  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202839/

    [Paper1]

    High level in vivo mucin-type glycosylation in Escherichia coli

  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681020/

    [Paper2]

    Core 2 mucin-type O-glycan inhibits EPEC or EHEC O157:H7 invasion into HT-29 epithelial cells

  6. https://academic.oup.com/bioinformatics/article/21/7/951/268976

    [Paper3]

    Protein homology detection by HMM–HMM comparison

  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907692/

    [Paper4]

    Global effect of RpoS on gene expression in pathogenic Escherichia coli O157:H7 strain EDL933

  8. https://pubmed.ncbi.nlm.nih.gov/31757694/

    [Paper5]

    Escherichia coli strains producing a novel Shiga toxin 2 subtype circulate in China

  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270005/

    [Paper7]

    Shiga Toxin (Stx) Classification, Structure, and Function

  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338595/

    [Paper8]

    A Novel Escherichia coli O157:H7 Clone Causing a Major Hemolytic Uremic Syndrome Outbreak in China

  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911697/

    [Paper10]

    Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins

  12. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30286-9

    [Paper11]

    The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens

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