Molecular characterization, antimicrobial resistance and clinico-bioinformatics approaches to address the problem of extended-spectrum β-lactamase-producing Escherichia coli in western Saudi Arabia. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Yasir, Muhammad; Ajlan, Abeer; Shakil, Shazi; Jiman-Fatani, Asif; Almasaudi, Saad; Farman, Muhammad; Baazeem, Zainah; Baabdullah, Rnda; Alawi, Maha; Al-Abdullah, Nabeela; Ismaeel, Nashat; Shukri, Hani; Azhar, Esam
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 11
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-33093-8
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract The goal of this study was to genotypically characterize extended-spectrum β-lactamase-producingEscherichia 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-producingE .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-producingE .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-positiveE .coli isolates primarily harbored thebla CTX-M andbla TEM genes. No resistance was observed against the carbapenem antibiotic group. All the ESBL-producingE .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-producingE .coli in this region.