Genomic Insights into Colistin-Resistant Klebsiella pneumoniae from a Tunisian Teaching Hospital

The emergence of colistin-resistant (CoR ) is a public health concern, since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) Gram negatives. In this study, we have investigated the molecular basis of colistin resistance in 13 MDR strains isola...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2018-02, Vol.62 (2)
Main Authors: Jaidane, Nadia, Bonnin, Rémy A, Mansour, Wejdene, Girlich, Delphine, Creton, Elodie, Cotellon, Garance, Chaouch, Cherifa, Boujaafar, Noureddine, Bouallegue, Olfa, Naas, Thierry
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Anti-Bacterial Agents - pharmacology
Bacterial Proteins - genetics
beta-Lactamases - genetics
Colistin
Colistin - pharmacology
Drug Resistance, Bacterial
Drug Resistance, Bacterial - genetics
Genome, Bacterial - genetics
Genomics - methods
Hospitals, Teaching - methods
Humans
Klebsiella Infections
Klebsiella Infections - drug therapy
Klebsiella Infections - microbiology
Klebsiella pneumoniae
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - genetics
Mechanisms of Resistance
Operon - genetics
Sequence Alignment
Tunisia
Whole Genome Sequencing - methods
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Summary:The emergence of colistin-resistant (CoR ) is a public health concern, since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) Gram negatives. In this study, we have investigated the molecular basis of colistin resistance in 13 MDR strains isolated from 12 patients in a teaching hospital in Sousse, Tunisia. Whole-genome sequencing (WGS) was used to decipher the molecular mechanism of colistin resistance and to identify the resistome of these CoR isolates. It revealed a genome of ca. 5.5 Mbp in size with a G+C content of 57%, corresponding to that commonly observed for These isolates belonged to the 5 different sequence types (ST11, ST15, ST101, ST147, and ST392), and their resistome was composed of acquired β-lactamases, including extended-spectrum beta-lactamase and carbapenemase genes ( , , , and genes), aminoglycoside resistance genes [ ( ') , ( ″)- , ( )- , and ( )- ], and fosfomycin ( ), fluoroquinolone ( -like), chloramphenicol, trimethoprim, and tetracycline resistance genes. All of the isolates were identified as having a mutated gene. Mapping reads with reference sequences of the most common genes involved in colistin resistance revealed several modifications in , , and operons (deletions, insertions, and substitutions) likely affecting the function of these proteins. It is worth noting that among the 12 patients, 10 were treated with colistin before the isolation of CoR No plasmid encoding to genes was found in these isolates. This study corresponds to the first molecular characterization of a collection of CoR strains in Tunisia and highlights that the small-transmembrane protein MgrB is a main mechanism for colistin resistance in .
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.01601-17