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  1. Article ; Online: Advances in Understanding Leishmania Pathobiology

    Tamara Salloum / Sima Tokajian / Robert P. Hirt

    Frontiers in Cell and Developmental Biology, Vol

    What Does RNA-Seq Tell Us?

    2021  Volume 9

    Abstract: Leishmaniasis is a vector-borne disease caused by a protozoa parasite from over 20 Leishmania species. The clinical manifestations and the outcome of the disease vary greatly. Global RNA sequencing (RNA-Seq) analyses emerged as a powerful technique to ... ...

    Abstract Leishmaniasis is a vector-borne disease caused by a protozoa parasite from over 20 Leishmania species. The clinical manifestations and the outcome of the disease vary greatly. Global RNA sequencing (RNA-Seq) analyses emerged as a powerful technique to profile the changes in the transcriptome that occur in the Leishmania parasites and their infected host cells as the parasites progresses through their life cycle. Following the bite of a sandfly vector, Leishmania are transmitted to a mammalian host where neutrophils and macrophages are key cells mediating the interactions with the parasites and result in either the elimination the infection or contributing to its proliferation. This review focuses on RNA-Seq based transcriptomics analyses and summarizes the main findings derived from this technology. In doing so, we will highlight caveats in our understanding of the parasite’s pathobiology and suggest novel directions for research, including integrating more recent data highlighting the role of the bacterial members of the sandfly gut microbiota and the mammalian host skin microbiota in their potential role in influencing the quantitative and qualitative aspects of leishmaniasis pathology.
    Keywords Leishmania ; RNA-Seq ; gene expression ; promastigotes ; amastigotes ; macrophages ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: SARS-CoV-2 and ORF3a

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

    mSystems, Vol 5, Iss 3, p e00266-

    Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis

    2020  Volume 20

    Abstract: 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 ...

    Abstract 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.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 3a protein ; covid-19 ; nonsynonymous mutations ; orf3a ; sars-cov-2 ; Microbiology ; QR1-502 ; covid19
    Subject code 572
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher American Society for Microbiology
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae Isolated from Lebanon

    Harout Arabaghian / Tamara Salloum / Sahar Alousi / Balig Panossian / George F. Araj / Sima Tokajian

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract Klebsiella pneumoniae is a Gram-negative organism and a major public health threat. In this study, we used whole-genome sequences to characterize 32 carbapenem-resistant K. pneumoniae (CRKP) and two carbapenem-resistant K. quasipneumoniae (CRKQ). ...

    Abstract Abstract Klebsiella pneumoniae is a Gram-negative organism and a major public health threat. In this study, we used whole-genome sequences to characterize 32 carbapenem-resistant K. pneumoniae (CRKP) and two carbapenem-resistant K. quasipneumoniae (CRKQ). Antimicrobial resistance was assessed using disk diffusion and E-test, while virulence was assessed in silico. The capsule type was determined by sequencing the wzi gene. The plasmid diversity was assessed by PCR-based replicon typing to detect the plasmid incompatibility (Inc) groups. The genetic relatedness was determined by multilocus sequence typing, pan-genome, and recombination analysis. All of the isolates were resistant to ertapenem together with imipenem and/or meropenem. Phenotypic resistance was due to bla OXA-48, bla NDM-1, bla NDM-7, or the coupling of ESBLs and outer membrane porin modifications. This is the first comprehensive study reporting on the WGS of CRKP and the first detection of CRKQ in the region. The presence and dissemination of CRKP and CRKQ, with some additionally having characteristics of hypervirulent clones such as the hypermucoviscous phenotype and the capsular type K2, are particularly concerning. Additionally, mining the completely sequenced K. pneumoniae genomes revealed the key roles of mobile genetic elements in the spread of antibiotic resistance and in understanding the epidemiology of these clinically significant pathogens.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Genome Mining and Comparative Analysis of Streptococcus intermedius Causing Brain Abscess in a Child

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

    Pathogens, Vol 8, Iss 1, p

    2019  Volume 22

    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 S. intermedius ; whole-genome ; T7SS ; GIs ; VFs ; SNPs ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Molecular characterization of Carbapenem resistant Escherichia coli recovered from a tertiary hospital in Lebanon.

    Christel Dagher / Tamara Salloum / Sahar Alousi / Harout Arabaghian / George F Araj / Sima Tokajian

    PLoS ONE, Vol 13, Iss 9, p e

    2018  Volume 0203323

    Abstract: The emergence of carbapenem resistant Escherichia coli represents a serious public health concern. This study investigated the resistome, virulence, plasmids content and clonality of 27 carbapenem resistant E. coli isolated from 27 hospitalized patients ... ...

    Abstract The emergence of carbapenem resistant Escherichia coli represents a serious public health concern. This study investigated the resistome, virulence, plasmids content and clonality of 27 carbapenem resistant E. coli isolated from 27 hospitalized patients at the American University of Beirut Medical Center (AUBMC) in Lebanon between 2012 and 2016. Whole-genome sequencing (WGS) data were used to identify resistance determinants. Multilocus sequence typing (MLST), pulsed field gel electrophoresis (PFGE), phylogenetic grouping and PCR-based replicon typing (PBRT) were also performed. The 27 isolates were distributed into 15 STs, of which ST405 (14.8%; n = 4) was the most prevalent. All of the 27 isolates were carbapenem resistant and 20 (74%) were extended-spectrum β-lactamase (ESBL) gene carriers. The predominant detected carbapenemases were blaOXA-48 (48.1%; n = 13) and blaOXA-181 (7.4%; n = 2), for the ESBLs it was blaCTX-M-15 (55.6%; n = 15) and blaCTX-M-24 (18.5%; n = 5), and for the AmpC-type β-lactamases, blaCMY-42 (40.7%; n = 11) and blaCMY-2 (3.7%; n = 1). Thirteen replicons were identified among the 27 E. coli isolates including: IncL/M, IncFIA, IncFIB, IncFII, IncI1, and IncX3. PFGE revealed a high genetic diversity with the 27 isolates being grouped in 21 different pulsotypes. SNPs analysis and PFGE showed a possible clonal dissemination of ST405, ST1284, ST354 and ST410 and the dominance of certain STs, monitoring of which could help in elucidating routes of transmission. This study represents the first WGS-based in depth analysis of the resistomes and mobilomes of carbapenem resistant E. coli in Lebanon.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex.

    Tamara Salloum / Rim Moussa / Ryan Rahy / Jospin Al Deek / Ibrahim Khalifeh / Rana El Hajj / Neil Hall / Robert P Hirt / Sima Tokajian

    PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e

    2020  Volume 0008684

    Abstract: Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding ... ...

    Abstract Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 572
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 [version 1; peer review

    Áine O'Toole / Verity Hill / Oliver G. Pybus / Alexander Watts / Issac I. Bogoch / Kamran Khan / Jane P. Messina / The COVID-19 Genomics UK (COG-UK) consortium / Network for Genomic Surveillance in South Africa (NGS-SA) / Brazil-UK CADDE Genomic Network / Houriiyah Tegally / Richard R. Lessells / Jennifer Giandhari / Sureshnee Pillay / Kefentse Arnold Tumedi / Gape Nyepetsi / Malebogo Kebabonye / Maitshwarelo Matsheka / Madisa Mine /
    Sima Tokajian / Hamad Hassan / Tamara Salloum / Georgi Merhi / Jad Koweyes / Jemma L. Geoghegan / Joep de Ligt / Xiaoyun Ren / Matthew Storey / Nikki E. Freed / Chitra Pattabiraman / Pramada Prasad / Anita S. Desai / Ravi Vasanthapuram / Thomas F. Schulz / Lars Steinbrück / Tanja Stadler / Swiss Viollier Sequencing Consortium / Antonio Parisi / Angelica Bianco / Darío García de Viedma / Sergio Buenestado-Serrano / Vítor Borges / Joana Isidro / Sílvia Duarte / João Paulo Gomes / Neta S. Zuckerman / Michal Mandelboim / Orna Mor / Torsten Seemann / Alicia Arnott

    Wellcome Open Research, Vol

    2 approved]

    2021  Volume 6

    Abstract: Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from ... ...

    Abstract Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Wellcome
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 with grinch [version 2; peer review

    Áine O'Toole / Verity Hill / Oliver G. Pybus / Alexander Watts / Issac I. Bogoch / Kamran Khan / Jane P. Messina / The COVID-19 Genomics UK (COG-UK) consortium / Network for Genomic Surveillance in South Africa (NGS-SA) / Brazil-UK CADDE Genomic Network / Houriiyah Tegally / Richard R. Lessells / Jennifer Giandhari / Sureshnee Pillay / Kefentse Arnold Tumedi / Gape Nyepetsi / Malebogo Kebabonye / Maitshwarelo Matsheka / Madisa Mine /
    Sima Tokajian / Hamad Hassan / Tamara Salloum / Georgi Merhi / Jad Koweyes / Jemma L. Geoghegan / Joep de Ligt / Xiaoyun Ren / Matthew Storey / Nikki E. Freed / Chitra Pattabiraman / Pramada Prasad / Anita S. Desai / Ravi Vasanthapuram / Thomas F. Schulz / Lars Steinbrück / Tanja Stadler / Swiss Viollier Sequencing Consortium / Antonio Parisi / Angelica Bianco / Darío García de Viedma / Sergio Buenestado-Serrano / Vítor Borges / Joana Isidro / Sílvia Duarte / João Paulo Gomes / Neta S. Zuckerman / Michal Mandelboim / Orna Mor / Torsten Seemann / Alicia Arnott

    Wellcome Open Research, Vol

    3 approved]

    2021  Volume 6

    Abstract: Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from ... ...

    Abstract Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Wellcome
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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