Whole-genome comparative analysis of carbapenem-resistant Escherichia coli isolated from hospitalized patients in Lebanon. (c2016)

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dc.contributor.author Dagher, Christel C.
dc.date.accessioned 2017-11-08T11:01:59Z
dc.date.available 2017-11-08T11:01:59Z
dc.date.copyright 2016 en_US
dc.date.submitted 2016-12-20
dc.identifier.uri http://hdl.handle.net/10725/6558
dc.description.abstract Antibiotic resistant bacteria that are challenging and nearly impossible to treat are becoming more prevalent and this is resulting in an urgent public health concern. The horizontal gene transfer of antibiotic resistance genes between bacteria as well as the complex antibiotic resistance mechanisms involved have aided in the production of an extensive spectrum of bacterial species with multi-drug resistant patterns. Resistance mechanisms of Gram-negative bacteria, such as extraintestinal Escherichia coli (ExPEC), vary extensively and the emergence of extended spectrum β-lactamases (ESBLs) as well as carbapenemases have compromised the effectiveness of the majority of antibiotics. ExPEC is one of the major causes of community- and nosocomial-acquired infections. Distinct from intestinal pathogens and commensals, ExPEC causes infections of the bloodstream, respiratory tract, urinary tract, peritoneum and cerebrospinal fluid. The universal burden of diseases caused by such a microorganism is staggering and hundreds of thousands of people are annually affected. In this study, 27 carbapenem resistant ExPEC isolates were recovered from hospitalized patients at the AUBMC (American University of Beirut Medical Center) and were used for identification, phylogenetic typing and molecular detection of associated antibiotic resistance genes (OXA, SHV, TEM, CTX-M and CTX-M-15). High-throughput sequencing was performed on ten isolates and bioinformatic tools were utilized to identify resistance and virulence determinants, plasmids, and phages. Overall, out of the 27 isolates, 59.6 %, 51.9 %, 7.4 %, 88.9 % and 63 % carried the blaOXA, blaTEM, blaSHV, blaCTX-M and blaCTX-M-15 genes, respectively. The distribution of the isolates among the different phylogenetic groups was as follows: 5 (18.5 %) belonged to group A, 3 (11.1 %) group B1, 6 (22.2 %) group B2 and 13 (48.2 %) group D. The average genome was 5.2 Mb with an average of 224–342 contigs and a G+C % content of 50.49 % – 50.79 %. The isolates were derived from 7 different lineages: ST- 405 (ECC153, ECC157, ECC173 and ECC188), ST-205 (EC 174), ST-410 (ECC194), ST-448 (ECC161), ST-617 (ECC202), ST-1284 (ECC167) and ST-648 (ECC149). Analysis revealed that these isolates harbored different β-lactamase genes including blaOXA-1, blaOXA-10, blaOXA-181, blaTEM-1b, blaCTX-M-15, blaCMY-2, blaCMY-42 in addition to aac(6')Ib-cr gene which confers tetracycline and aminoglycoside resistance among others. To the best of our knowledge, this is the first detection of blaOXA-181 encoding E. coli from Lebanon in addition to it being the first comprehensive genome-wide comparative analysis of carbapenem resistant ExPEC isolates. The pandemic potential of these ExPEC strains merits further large-scale comparative and functional genomic studies to better understand the biology of this clinically important bacterium. en_US
dc.language.iso en en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.subject Escherichia coli infections -- Immunological aspects en_US
dc.subject Drug resistance in microorganisms en_US
dc.subject Escherichia coli -- Lebanon en_US
dc.title Whole-genome comparative analysis of carbapenem-resistant Escherichia coli isolated from hospitalized patients in Lebanon. (c2016) en_US
dc.type Thesis en_US
dc.term.submitted Fall en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201100165 en_US
dc.author.commembers Khalaf, Roy
dc.author.commembers Nawas, Tarek
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc 1 hard copy: xv, 101 leaves; 30 cm. available at RNL. en_US
dc.author.advisor Tokajian, Sima
dc.keywords Escherichia coli en_US
dc.keywords ExPEC en_US
dc.keywords ESBL en_US
dc.keywords Carbapenem Resistance en_US
dc.keywords High Throughput Sequencing en_US
dc.keywords Lebanon en_US
dc.keywords Virulence en_US
dc.keywords CTX-M-15 en_US
dc.keywords OXA-181 en_US
dc.description.bibliographiccitations Bibliography : leaves 55-73. en_US
dc.identifier.doi https://doi.org/10.26756/th.2017.23 en_US
dc.author.email christel.dagher@lau.edu en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US

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