Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 6.4-kb DNA fragment containing the DNA gyrase gyrA and gyrB genes was cloned and sequenced from the quinolone-susceptible Staphylococcus aureus type strain ATCC 12600. An expression plasmid was constructed by inserting the cloned genes into the Escherichia coli-S. aureus shuttle vector pAT19, and deletion plasmids carrying only functional gyrA and gyrB genes were derived from this plasmid. An efficient transformation system for S. aureus RN4220 was established by using these plasmids. Quinolone-resistant mutants of S. aureus RN4220 were isolated by three-step selection with quinolones. The first- and second-step mutants were considered to be transport mutants, and the third-step mutants were divided into five groups with respect to their resistance patterns and transformation results with gyrA and gyrB genes. Sequencing analysis of the resulting mutant gyrase genes showed that they had the following point mutations: group 1, Ser-84 (TCA) to Leu (TTA) in GyrA; group 2, Ser-84 (TCA) to Ala (GCA), Ser-85 (TCT) to Pro (CCT), or Glu-88 (GAA) to Lys (AAA) in GyrA; group 3, Asp-437 (GAC) to Asn (AAC) in GyrB; group 4, Arg-458 (CGA) to Gln (CAA) in GyrB; and group 5, Ser-85 (TCT) to Pro (CCT) in GyrA and Asp-437 (GAC) to Asn (AAC) in GyrB. When the gyrA and/or gyrB mutants were transformed with the wild-type gyrA and/or gyrB plasmids, they became quinolone susceptible, but transformants with the plasmids having the same mutations on the gyrA and/or gyrB genes did not confer susceptibility. These results indicate that mutations in both gyrA and gyrB can be responsible for quinolone resistance in S. aureus.
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PMID:Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. 781 Oct 12

Ofloxacinresistance in Staphylococcus aureus is achieved through 2 sequential events of genetic alteration. The second-step mutation has been identified as that of DNA gyrase, but the first-step mutation for norfloxacin resistance and low-level ofloxacin resistance has not yet been identified. In this paper, we report that single point mutations of grIA, which encodes for the A subunit of topoisomerase IV (GrIA), are found in all of the norfloxacin-resistant first-step in vitro mutants of S. aureus as well as in quinolone-resistant clinical S. aureus strains. The amino acid substitution of the GrIA was Ser-80 (TCC) to Tyr (TAC) or the (TTC), Glu-84 (GAA) to Lys (AAA), or Ala-116 (GCA) to Glu (GAA). The GCA to GAA mutation at codon 116 is a novel mutation, and may be responsible for higher quinoloneresistance than with the other grIA mutations.
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PMID:The grIA Mutation in Norfloxacin-Resistant First-Step Mutants and Clinical Isolates of Staphylococcus aureus. 2968 57