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Article: SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis.

Issa, Elio / Merhi, Georgi / Panossian, Balig / Salloum, Tamara / Tokajian, Sima

mSystems

2020 Volume 5, Issue 3

Abstract: The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our ... ...

Abstract	The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation.
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	United States
Document type	Journal Article
ISSN	2379-5077
ISSN	2379-5077
DOI	10.1128/mSystems.00266-20
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genomic Features of

Fattel, Leila / Panossian, Balig / Salloum, Tamara / Abboud, Edmond / Tokajian, Sima

Foodborne pathogens and disease

2019 Volume 16, Issue 11, Page(s) 778–787

Abstract: Gastroenteritis is a disease that can be caused by virulent strains ... ...

Abstract	Gastroenteritis is a disease that can be caused by virulent strains of
MeSH term(s)	Bacterial Toxins/analysis ; Disease Outbreaks ; Drug Resistance, Bacterial ; Feces/microbiology ; Foodborne Diseases/epidemiology ; Foodborne Diseases/microbiology ; Gastroenteritis/microbiology ; Hemolysin Proteins/analysis ; Humans ; Lebanon/epidemiology ; Multilocus Sequence Typing ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Vibrio Infections/epidemiology ; Vibrio Infections/microbiology ; Vibrio parahaemolyticus/classification ; Vibrio parahaemolyticus/genetics ; Vibrio parahaemolyticus/pathogenicity ; Virulence/genetics ; Whole Genome Sequencing
Chemical Substances	Bacterial Toxins ; Hemolysin Proteins ; thermostable direct hemolysin (135433-21-5)
Language	English
Publishing date	2019-07-08
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2148479-X
ISSN	1556-7125 ; 1535-3141
ISSN (online)	1556-7125
ISSN	1535-3141
DOI	10.1089/fpd.2018.2618
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Article ; Online: First report of plasmid-mediated colistin resistance mcr-8.1 gene from a clinical Klebsiella pneumoniae isolate from Lebanon.

Salloum, Tamara / Panossian, Balig / Bitar, Ibrahim / Hrabak, Jaroslav / Araj, George F / Tokajian, Sima

Antimicrobial resistance and infection control

2020 Volume 9, Issue 1, Page(s) 94

Abstract: Colistin is considered as a last resort treatment for infections caused by multidrug-resistant Enterobacteriaceae. Plasmid-mediated mobile colistin resistance (mcr) genes contributed to the global spread of colistin resistance. This is the first report ... ...

Abstract	Colistin is considered as a last resort treatment for infections caused by multidrug-resistant Enterobacteriaceae. Plasmid-mediated mobile colistin resistance (mcr) genes contributed to the global spread of colistin resistance. This is the first report of plasmid-mediated colistin resistance mcr-8 gene from a clinical Klebsiella pneumoniae K9 isolate recovered from Lebanon. The isolate was characterized phenotypically and genotypically through both short and long read whole-genome sequencing, plasmid typing and conjugation assays. k9 belonged to sequence type 15 and harbored 31 antimicrobial resistance genes. The mcr-8.1 variant was carried on a novel ~ 300 kb multireplicon plasmid having IncFIA, IncR and IncHI1B. The plasmid was conjugative and carried a plethora of antimicrobial resistance determinants. The introduction of novel mcr variants in Lebanon poses an alarming health concern. Surveillance and screening for colistin resistant Enterobacteriaceae and mcr in livestock, animal farms, imported meat and poultry is highly recommended along with monitoring antibiotic use.
MeSH term(s)	Bacterial Proteins/genetics ; Colistin/pharmacology ; Female ; Genome Size ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/genetics ; Klebsiella pneumoniae/isolation & purification ; Lebanon ; Microbial Sensitivity Tests ; Middle Aged ; Plasmids/genetics ; Whole Genome Sequencing
Chemical Substances	Bacterial Proteins ; Colistin (Z67X93HJG1)
Language	English
Publishing date	2020-06-26
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2666706-X
ISSN	2047-2994 ; 2047-2994
ISSN (online)	2047-2994
ISSN	2047-2994
DOI	10.1186/s13756-020-00759-w
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Article ; Online: Detailed characterization of an IncFII plasmid carrying blaOXA-48 from Lebanon.

Moussa, Jennifer / Panossian, Balig / Nassour, Elie / Salloum, Tamara / Abboud, Edmond / Tokajian, Sima

The Journal of antimicrobial chemotherapy

2020 Volume 75, Issue 9, Page(s) 2462–2465

Abstract: Background: The spread of carbapenem-resistant Enterobacteriaceae is an important challenge and an increasing healthcare problem. OXA-48 is a class D carbapenemase that is usually localized on a conjugative plasmid belonging to the IncL incompatibility ... ...

Abstract	Background: The spread of carbapenem-resistant Enterobacteriaceae is an important challenge and an increasing healthcare problem. OXA-48 is a class D carbapenemase that is usually localized on a conjugative plasmid belonging to the IncL incompatibility group. Methods: In this study, we used a combination of short- and long-read WGS approaches and molecular typing techniques to characterize the genetic environment of the smallest reported 27 029 bp IncFII plasmid carrying blaOXA-48 (pLAU-OXA48). Results: The plasmid recovered from a clinical Escherichia coli isolate was positive for blaOXA-48, which was located within the Tn6237 composite transposon. Primers targeting junctions between the IncF fragment and Tn6237 for the rapid identification of pLAU-OXA48-like plasmids were designed. Conclusions: To our knowledge, this is the first report showing the complete sequence of an IncFII plasmid carrying blaOXA-48 within Tn6237 using hybrid assembly of long- and short-read sequencing.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Carbapenem-Resistant Enterobacteriaceae ; Escherichia coli/genetics ; Lebanon ; Microbial Sensitivity Tests ; Plasmids/genetics ; beta-Lactamases/genetics
Chemical Substances	Anti-Bacterial Agents ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2020-05-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkaa181
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A dynamic epibiont community associated with the bone-eating polychaete genus

Goffredi, Shana K / Panossian, Balig / Brzechffa, Camille / Field, Naomi / King, Chad / Moggioli, Giacomo / Rouse, Greg W / Martín-Durán, José M / Henry, Lee M

mBio

2023 Volume 14, Issue 4, Page(s) e0314022

Abstract: Osedax, ...

Abstract	Osedax,
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03140-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Genome Mining and Comparative Analysis of <i>Streptococcus intermedius</i> Causing Brain Abscess in a Child

Issa, Elio / Salloum, Tamara / Panossian, Balig / Ayoub, David / Abboud, Edmond / Tokajian, Sima

Pathogens. 2019 Feb. 13, v. 8, no. 1

2019

Abstract: Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are ... ...

Abstract	Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are understudied. We performed a whole-genome comparative analysis of an SI isolate, LAU_SINT, associated with brain abscess following sinusitis with all SI genomes in addition to S. constellatus and S. anginosus. Selective pressure on virulence factors, phages, pan-genome evolution and single-nucleotide polymorphism analysis were assessed. The structural details of the type seven secretion system (T7SS) was elucidated and compared with different organisms. ily and nanA were both abundant and conserved. Nisin resistance determinants were found in 47% of the isolates. Pan-genome and SNPs-based analysis didn’t reveal significant geo-patterns. Our results showed that two SC isolates were misidentified as SI. We propose the presence of four T7SS modules (I–IV) located on various genomic islands. We detected a variety of factors linked to metal ions binding on the GIs carrying T7SS. This is the first detailed report characterizing the T7SS and its link to nisin resistance and metal ions binding in SI. These and yet uncharacterized T7SS transmembrane proteins merit further studies and could represent potential therapeutic targets.
Keywords	Streptococcus anginosus ; Streptococcus constellatus ; Streptococcus intermedius ; abscess ; antibiotic resistance ; brain ; children ; evolution ; genome mining ; genomic islands ; metal ions ; nisin ; phages ; secretion ; single nucleotide polymorphism ; sinusitis ; survival rate ; therapeutics ; transmembrane proteins ; virulence
Language	English
Dates of publication	2019-0213
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens8010022
Database	NAL-Catalogue (AGRICOLA)

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Article: Genomic Features of Vibrio parahaemolyticus from Lebanon and Comparison to Globally Diverse Strains by Whole-Genome Sequencing

Fattel, Leila / Abboud, Edmond / Panossian, Balig / Salloum, Tamara / Tokajian, Sima

Foodborne pathogens & disease. 2019 Nov. 01, v. 16, no. 11

2019

Abstract: Gastroenteritis is a disease that can be caused by virulent strains of Vibrio parahaemolyticus in humans upon the consumption of contaminated seafood. In summer 2017, a sudden increase in the number of patients suffering from gastroenteritis due to a V. ... ...

Abstract	Gastroenteritis is a disease that can be caused by virulent strains of Vibrio parahaemolyticus in humans upon the consumption of contaminated seafood. In summer 2017, a sudden increase in the number of patients suffering from gastroenteritis due to a V. parahaemolyticus infection was observed at the Middle East Institute of Health University Hospital in Lebanon. The aim of this study was to analyze the isolates recovered from stool specimens, and to compare them using different phenotypic assays, genomic profiling techniques, and whole-genome sequencing, to achieve a better understanding of the current V. parahaemolyticus strains available in Lebanon. Virulence potential was analyzed based on the detection of the hemolysins: thermostable direct hemolysin (tdh), thermostable direct hemolysin-related hemolysin (trh), and thermolabile hemolysin (tlh). Resistance was determined by testing antibiotic susceptibility and performing PCR assays for β-lactamases and quinolone resistance determinants. Genetic relatedness was verified by multilocus sequence typing, pulsed-field gel electrophoresis, and whole genome-based single nucleotide polymorphism analysis. All of the isolates had the tdh+, trh−, group-specific PCR+ genotype, which is a characteristic of the O3:K6 pandemic clone. The isolates were resistant to ampicillin (100%), ceftazidime (86%), ticarcillin (14%), and amikacin (14%), belonged to the sequence type ST3, and had very similar phylogenetic fingerprints. The isolates undertaken in this study exhibited almost identical resistance, virulence, and phylogenetic patterns, confirming an outbreak linked to the spread of the pandemic O3:K6 serotype in the country.
Keywords	amikacin ; ampicillin ; antibiotic resistance ; beta-lactamase ; ceftazidime ; feces ; gastroenteritis ; genetic relationships ; genomics ; genotype ; hemolysins ; hospitals ; multilocus sequence typing ; pandemic ; patients ; phenotype ; phylogeny ; polymerase chain reaction ; pulsed-field gel electrophoresis ; quinolones ; seafood contamination ; serotypes ; single nucleotide polymorphism ; summer ; thermal stability ; ticarcillin ; Vibrio parahaemolyticus ; virulence ; virulent strains ; Lebanon ; Middle East
Language	English
Dates of publication	2019-1101
Size	p. 778-787.
Publishing place	Mary Ann Liebert, Inc.
Document type	Article
ZDB-ID	2148479-X
ISSN	1556-7125 ; 1535-3141
ISSN (online)	1556-7125
ISSN	1535-3141
DOI	10.1089/fpd.2018.2618
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions

Issa, Elio / Merhi, Georgi / Panossian, Balig / Salloum, Tamara / Tokajian, Sima

bioRxiv

Abstract: The effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and ... ...

Abstract	The effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and their role in evading the immune response, nucleotide and protein sequences of 537 available SARS-CoV-2 genomes were analyzed for the presence of non-synonymous mutations and polyproline regions. Mutations were correlated with changes in epitope formation. A total of 19 different non-synonymous amino acids substitutions were detected in ORF3a among 537 SARS-CoV-2 strains. G251V was the most common and identified in 9.9% (n=53) of the strains and was predicted to lead to the loss of a B-cell like epitope in ORF3a. Polyproline regions were detected in two strains (EPI_ISL_410486, France and EPI_ISL_407079, Finland) and affected epitopes formation. The accumulation of non-synonymous mutations and detected polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread. Rapid mutations accumulating in ORF3a should be closely monitored throughout the COVID-19 pandemic. Importance At the surge of the COVID-19 pandemic and after three months of the identification of SARS-CoV-2 as the disease-causing pathogen, nucleic acid changes due to host-pathogen interactions are insightful into the evolution of this virus. In this paper, we have identified a set of non-synonymous mutations in ORF3a and predicted their impact on B-cell like epitope formation. The accumulation of non-synonymous mutations in ORF3a could be driving protein changes that mediate immune evasion and favoring viral spread.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.03.27.012013
Database	COVID19

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Article: SARS-CoV-2 and ORF3a: Nonsynonymous mutations, functional domains, and viral pathogenesis

Issa, Elio / Merhi, Georgi / Panossian, Balig / Salloum, Tamara / Tokajian, Sima

mSystems

Abstract	The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARSCoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation. Importance_ At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #186342
Database	COVID19

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Article ; Online: SARS-CoV-2 and ORF3a

Issa, Elio / Merhi, Georgi / Panossian, Balig / Salloum, Tamara / Tokajian, Sima

mSystems

Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis

2020 Volume 5, Issue 3

Abstract: ABSTRACT The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. ...

Abstract	ABSTRACT The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein’s structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation. IMPORTANCE At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.
Keywords	covid19
Language	English
Publisher	American Society for Microbiology
Publishing country	us
Document type	Article ; Online
ISSN	2379-5077
DOI	10.1128/msystems.00266-20
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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