Disease relevance of grlB

• A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced [1].

High impact information on grlB

• This study provides the first genetic and biochemical data supporting the dual targeting of topoisomerase IV and gyrase in S. aureus by a quinolone as well as providing genetic proof for the expansion of the QRDRs to include the 5' terminus of grlB and the 3' terminus of gyrA [2].
• The presence of wild-type grlB-grlA gene sequences in second-step mutants excluded involvement of topoisomerase IV in the small-colony phenotype [3].
• A 4.2-kb DNA fragment conferring quinolone resistance was cloned from a quinolone-resistant clinical isolate of Staphylococcus aureus and was shown to possess a part of the grlB gene and a mutated grlA gene [4].
• No mutants had any changes in grlB, and only one had a mutation in gyrB giving rise to the novel substitution Asp-437-->His [5].

Biological context of grlB

• However, dominance by mutated grlA genes depended on gene dosage when bacteria were transformed with the grlA and grlB genes in combination [4].

Associations of grlB with chemical compounds

• A double mutation (gyrA and either grlA or grlB) caused a 32-fold increase in the MIC of premafloxacin, while the MIC of ciprofloxacin increased 128-fold [6].
• The inhibitory activities of fluoroquinolones against the topoisomerase IV which contained a single amino acid change (Ser --> Phe at codon 80, Glu --> Lys at codon 84 of grlA, and Asp --> Asn at codon 432 of grlB) were from 5 to 95 times weaker than the inhibitory activities against the non-altered enzyme [7].

Other interactions of grlB

• Only two gyrB mutants and one grlB mutant were observed among the isolates: all contained a previously unreported mutation [8].

References