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Biomedical subjects

J C Nguyen Van

Publications and source records attributed to J C Nguyen Van.

5 recordsLinked to original sources

A novel, double mutation in DNA gyrase A of Escherichia coli conferring resistance to quinolone antibiotics.

A spontaneous Escherichia coli mutant, named Q3, resistant to nalidixic acid was obtained from a previously described clinical isolate of E. coli, Q2, resistant to fluoroquinolones but susceptible to nalidixic acid (E. Cambau, F. Bordon, E. Collatz, and L. Gutmann, Antimicrob. Agents Chemother. 37:1247-1252, 1993). Q3 harbored the mutation Asp82Gly in addition to the Gly81Asp mutation of Q2. The different mutations leading to Gly81Asp, Asp82Gly, and Gly81AspAsp82Gly were introduced into the gyrA gene harbored on plasmid pJSW102, and the resulting plasmids were introduced into E. coli KNK453 (gyrAts) by transformation. The presence of Asp82Gly or Gly81Asp alone led to a low-level resistance to fluoroquinolones but not to nalidixic acid resistance. When both mutations were present, resistance to both nalidixic acid and fluoroquinolones was expressed. Purified gyrases of the different mutants showed similar rates of supercoiling. Dominance of the various gyrA mutant alleles harbored on plasmids was examined. The susceptibility to quinolones associated with wild-type gyrA was always dominant. The susceptibility to nalidixic acid expressed by the Gly81Asp mutant was dominant, while that expressed by the Asp82Gly mutant was recessive. From these results, we hypothesize that some amino acids within the quinolone resistance-determining region of gyrase A are more important for the association of subunits rather than for the activity of the holoenzyme.

Anti-Infective Agents↗

[Resistance to antibiotics caused by decrease of the permeability in gram-negative bacteria].

Due to their outer membrane, Gram negative bacteria are the only germs which can resist antibiotics by a mechanism of reduced permeability. This outer hydrophobic membrane allows hydrophilic molecules to pass only through its aqueous pores. The transmembrane pores have a trimere structure with a monomere component acting as an aqueous channel. Mean pore diameter is 1 to 1.2 nm. Changes in the absolute number of pores or in qualitative function reduce the diffusion of antibiotics entering the cell. This mechanism of reduced permeability can lead to cross resistance to several families of antibiotics. It is difficult to determine the clinical incidence since such resistances are not always detected. The species most often involved are enterobacteria including Klebsiella, Enterobacter, Serratia and Salmonella. For Pseudomonas aeruginosa, resistance to imipenem by reduced permeability results from a deficit in protein D2 and concerns 12 to 15% of the strains identified in French Hospitals. Reduced permeability is particularly effective when associated with another mechanism of resistance allowing the bacteria to express a higher level of resistance.

4-Quinolones↗