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1.
Sci Rep ; 8(1): 14847, 2018 10 04.
Article in English | MEDLINE | ID: mdl-30287889

ABSTRACT

The goal of this study was to genotypically characterize extended-spectrum ß-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 blaCTX-M and blaTEM 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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Computational Biology , Drug Resistance, Bacterial , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli Proteins/biosynthesis , Escherichia coli/drug effects , Escherichia coli/genetics , Membrane Proteins/biosynthesis , Adolescent , Adult , Alleles , Anti-Bacterial Agents/chemistry , Child , Child, Preschool , Computational Biology/methods , Escherichia coli/classification , Escherichia coli Proteins/chemistry , Escherichia coli Proteins/genetics , Female , Genome, Bacterial , Genotype , Geography , Humans , Infant , Infant, Newborn , Male , Membrane Proteins/chemistry , Membrane Proteins/genetics , Microbial Sensitivity Tests , Middle Aged , Molecular Conformation , Molecular Docking Simulation , Molecular Dynamics Simulation , Multilocus Sequence Typing , Protein Binding , Saudi Arabia/epidemiology , Whole Genome Sequencing , Young Adult
2.
BMC Microbiol ; 15: 65, 2015 Mar 14.
Article in English | MEDLINE | ID: mdl-25888310

ABSTRACT

BACKGROUND: Saudi Arabia is mostly barren except the southwestern highlands that are susceptible to environmental changes, a hotspot for biodiversity, but poorly studied for microbial diversity and composition. In this study, 454-pyrosequencing of 16S rRNA gene hypervariable region V6 was used to analyze soil bacterial community along elevation gradients of the southwestern highlands. RESULTS: In general, lower percentage of total soil organic matter (SOM) and nitrogen were detected in the analyzed soil samples. Total 33 different phyla were identified across the samples, including dominant phyla Proteobacteria, Actinobacteria and Acidobacteria. Representative OTUs were grouped into 329 and 508 different taxa at family and genus level taxonomic classification, respectively. The identified OTUs unique to each sample were very low irrespective of the altitude. Jackknifed principal coordinates analysis (PCoA) revealed, overall differences in the bacterial community were more related to the quantity of specific OTUs than to their diversity among the studied samples. CONCLUSIONS: Bacterial diversity and soil physicochemical properties did not show consistent changes along the elevation gradients. The large number of OTUs shared between the studied samples suggest the presence of a core soil bacterial community in the southwestern highlands of Saudi Arabia.


Subject(s)
Altitude , Bacteria/classification , Bacteria/genetics , Microbiota , Soil Microbiology , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Metagenome , Molecular Sequence Data , Phylogeny , RNA, Ribosomal, 16S/genetics , Saudi Arabia , Sequence Analysis, DNA
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