Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) are the two essential type II topoisomerases in Escherichia coli. These enzymes act via inhibition of DNA replication. Mutations in the quinolone resistance-determining region (QRDR) of the gyrA, gyrB, parC and parE genes from clinical isolates of E. coli were determined by DNA sequencing of 54 ciprofloxacin-resistant clinical isolates from a hospital in Delhi, India. The majority of the E. coli isolates were shown to carry mutations in gyrA, parC and parE. Ciprofloxacin resistance due to accumulation of such a high number of mutations in the QRDR regions of gyrA at positions Ser83 and Asp87 and parC at position Ser80 as well as outside of the QRDR region of parE at Ser458 and Glu460 confers high-level resistance of ciprofloxacin in clinical isolates. The high frequency of occurrence of mutations in the parE gene (44.4% strains) is alarming, as topoisomerase IV is a secondary target of quinolones.
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PMID:Contribution of mutations in DNA gyrase and topoisomerase IV genes to ciprofloxacin resistance in Escherichia coli clinical isolates. 2123 44

Antimicrobial resistance happens when microorganisms mutates in manners that render the drugs like antibacterial, antiviral, antiparasitic and antifungal, ineffective. The normal mutation process is encouraged by the improper use of antibiotics. Mutations leading to quinolone resistance occur in a highly conserved region of the quinolone resistance-determining region (QRDR) of DNA gyrAse and topoisomerase IV gene. We analyzed antibiotic resistant genes and single nucleotide polymorphism (SNP) in gyrA and parC genes in QRDR in 120 E. coli isolates (both diarrheagenic and non-pathogenic) recovered from fresh stool samples collected from children aged less than 5 years from Delhi, India. Antibiotic susceptibility testing was performed according to standard clinical and laboratory standards institute (CLSI) guidelines. Phylogenetic analysis showed the clonal diversity and phylogenetic relationships among the E. coli isolates. The SNP analysis depicted mutations in gyrA and parC genes in QRDR. The sul1 gene, responsible for sulfonamide resistance, was present in almost half (47.5%) of the isolates across the diseased and healthy samples. The presence of antibiotic resistance genes in E. coli isolates from healthy children indicate the development, dissemination and carriage of antibiotic resistance in their gut. Our observations suggest the implementation of active surveillance and stewardship programs to promote appropriate antibiotic use and minimizing further danger.
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PMID:Changing paradigm of antibiotic resistance amongst Escherichia coli isolates in Indian pediatric population. 3099 25