Molecular characterization, antimicrobial resistance and clinico-bioinformatics approaches to address the problem of extended-spectrum β-lactamase-producing Escherichia coli in western Saudi Arabia.

Autor:	Yasir M; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. yasirkhattak.mrl@gmail.com., Ajlan AM; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Biology Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Shakil S; Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Jiman-Fatani AA; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Clinical and molecular microbiology laboratories King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Almasaudi SB; Biology Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Farman M; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Biology Department, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Baazeem ZM; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Baabdullah R; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Alawi M; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Infection Control & Environmental Health Unit, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Abdullah N; Infection Control & Environmental Health Unit, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Public Health, Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia., Ismaeel NA; Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Shukri HA; Clinical and molecular microbiology laboratories King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Azhar EI; Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 Oct 04; Vol. 8 (1), pp. 14847. Date of Electronic Publication: 2018 Oct 04.
DOI:	10.1038/s41598-018-33093-8
Abstrakt:	The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producing Escherichia coli isolates from the western region of Saudi Arabia and to identify active antibiotics against these isolates using phenotypic and molecular modeling. In total, 211 ESBL-producing E. coli isolates recovered from heterogeneous clinical specimens were identified by MALDI-TOF. Thirty-two sequence types (STs) were identified from a multilocus sequence typing (MLST) analysis of ESBL-producing E. coli, including a novel ST (ST8162). The most common ST in the Saudi and expatriate population was ST131, followed by ST38. All the isolates were multidrug resistant (MDR), and >95% of the isolates were resistant to third-generation (ceftriaxone and ceftazidime) and fourth-generation (cefepime) cephalosporins. The ESBL-positive E. coli isolates primarily harbored the bla CTX-M and bla TEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producing E. coli isolates were observed to be susceptible to a ceftazidime/avibactam combination. Molecular interaction analyses of the docked complexes revealed the amino acid residues crucial for the binding of antibiotics and inhibitors to the modeled CTX-M-15 enzyme. Importantly, avibactam displayed the most robust interaction with CTX-M-15 among the tested inhibitors in the docked state (∆G = -6.6 kcal/mol). The binding free energy values for clavulanate, tazobactam and sulbactam were determined to be -5.7, -5.9 and -5.2 kcal/mol, respectively. Overall, the study concludes that 'ceftazidime along with avibactam' should be carefully used as a treatment option against only carbapenem-resistant MDR ESBL-producing E. coli in this region.
Databáze:	MEDLINE
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