Biology subjects

Tokajian, S.

Publications and source records attributed to Tokajian, S..

3 recordsLinked to original sources

bioRxiv2024

Emerging Mycobacterium bovis in Lebanon: a snapshot based on whole-genome sequencing.

BackgroundTuberculosis is a pressing public health issue in Lebanon, a country of approximately five million people, including around 1.5 million refugees from Palestine and Syria. Prior research has revealed uncontrolled animal sources of Mycobacterium bovis, emphasizing the necessity for a comprehensive approach to combat tuberculosis in the region. Methods48 clinical Mycobacterium tuberculosis complex isolates were identified through whole genome sequence. Also, 43 animal fecal samples were collected from various farms across Lebanon to investigate the presence of the M. tuberculosis complex using CRISPR-csm4 PCR. ResultsGenomic analysis revealed that 39/48 (81.25%) of isolates were M. tuberculosis and 9/48 (18.75%) were M. bovis. M. tuberculosis was distributed over four lineages, Indo-Oceanic L1 (n = 3/39)(7.6%), East-Asian L2 (n = 1/39)(2.5%), East-African Indian L3 (n = 5/39)(12.8%) and Euro-American L4 (n = 30/39)(76.9%). Sub-lineage L4.8 (Euro-American (mainly T), comprising 8/39 of the isolates (20.5%) was predominant, followed by sub-lineages L3 (East-African Indian, n = 5/39 isolates)(12.8%), L4.2.2.2 (Euro-American (Ural), n= 4/39 isolates)(10.2%) and L4.6.5 (Euro American, n=4/39 isolates)(10.2%). Nine M. bovis were classified into two clades, designated as unknown2 (n=2/9; 22.2%) and unknown3 (n=7/9; 77.8%). Interestingly, none of the clades or others were detected in the 48 faecal samples using CRISPR standard PCR and qPCR. ConclusionsThis study offers insights into human and bovine tuberculosis in Lebanon, emphasizing M. tuberculosis lineages prevalence and M. bovis distribution into two clades, aiding the fight against tuberculosis, especially bovine tuberculosis, and renewing our understanding of tuberculosis dynamics in Lebanon.

microbiology↗

bioRxiv2023

Genetic and Structural Basis of Colistin Resistance in Klebsiella pneumoniae: Unraveling the Molecular Mechanisms

Antimicrobial Antimicrobial resistance (AMR), together with extensively drug resistant (XDR), mainly among Gram-negative bacteria, has been on the rise. Colistin (polymyxin E) remains one of the primary available last resorts to treat infections by XDR bacteria with the rapid emergence of global resistance. Since the exact mechanism of bacterial resistance to colistin remains unfolded, this study warranted elucidating the underlying mechanism of colistin resistance and heteroresistance among carbapenem-resistant (CR) Klebsiella pneumoniae isolates. Molecular analysis was carried out on the resistant isolates using a genome-wide characterization approach, and MALDI-TOF MS for lipid A. Among the 32 CR K. pneumoniae isolates, three and seven isolates showed resistance and intermediate resistance, respectively, to colistin. The seven isolates with intermediate resistance exhibited the "skip-well" phenomenon, attributed to the presence of resistant subpopulations. The three isolates with full resistance to colistin showed ions using MALDI-TOF MS at m/z 1840 and 1824 representing bisphosphorylated and hexaacylated lipid A with or without hydroxylation, at position C-2 of the fatty acyl chain, respectively. Studying the genetic environment of mgrB locus revealed the presence of insertion sequences that disrupted the mgrB locus in the three colistin resistant isolates: IS1R and IS903B. Our findings showed that colistin resistance/heteroresistance was inducible with mutations in chromosomal regulatory networks controlling lipid A moiety and IS sequences disrupting the mgrB gene leading to elevated MIC values and treatment failure. IS monitoring in K. pneumoniae could help prevent the spread of colistin resistance and decrease colistin treatment failure.

genomics↗

bioRxiv2022

Whole genome-based characterization of multi-drug resistant Enterobacter and Klebsiella aerogenes isolates from Lebanon

BackgroundEnterobacter spp. are rod-shaped Gram-negative opportunistic pathogens belonging to Enterobacterales. This study aimed at the molecular and genomic characterization of multi-drug resistant Enterobacter spp. isolates recovered from hospitalized patients in a tertiary care hospital in Lebanon. MaterialsA total of 59 Enterobacter spp. clinical isolates consisting of 41 carbapenem-resistant and 18 susceptible by E-test were included in this study. Genotypic identification through whole-genome sequencing was performed and confirmed in silico. Resistance and plasmid profiles were studied using ResFinder4.0 and Plasmid-Finder2.1. Multi-locus sequence typing (MLST) was used to determine the isolates clonality. ResultsANI identified and confirmed that 47 (80%) isolates were E. hormaechei, 11 (18%) were Klebsiella aerogenes and 1 (2%) was an E. cloacae. Carbapenem-resistance was detected among 41 isolates all showing an MIC90 of [≥] 32 {micro}g/ml for ertapenem, imipenem, and meropenem. blaNDM-1 (58.5%), blaACT-16 (54%), and blaOXA-1 (54%) were the most common detected {beta}-lactamases, while blaCTX-M-15 gene (68%) was the main detected extended-spectrum {beta}-lactamase (ESBL) encoding gene. Chromosomal ampC gene, carbapenemase encoding genes, and porin modifications were among the detected carbapenem resistance determinants. The carbapenemase encoding genes were linked to three well-defined plasmid Inc groups, IncFII/IncFIB, IncX3, and IncL. MLST typing revealed the diversity within the studied isolates, with ST114 being the most common amongst the studied E. hormaechei. ConclusionThe spread of carbapenem-resistant isolates in clinical settings in Lebanon is a serious challenge. Screening and continuous monitoring through WGS analysis could effectively limit the dissemination of drug-resistant isolates in hospitalized patients. ImportanceDrug resistance is an increasing global public health threat that involves most disease-causing organisms and antimicrobial drugs. Drug-resistant organisms spread in healthcare settings, and resistance to multiple drugs is common. Our study demonstrated the mechanisms leading to resistance against the last resort antimicrobial agents among members of the Enterobacteriaceae family. The spread of carbapenem-resistant bacteria in clinical settings is a serious challenge. Screening and continuous monitoring could effectively limit the dissemination of drug-resistant isolates in hospitalized patients.

genomics↗