High-Level Chromosomally Mediated Tetracycline Resistance inNeisseria gonorrhoeaeResults from a Point Mutation in therpsJGene Encoding Ribosomal Protein S10 in Combination with themtrRandpenBResistance Determinants

• DOI: 10.1128/aac.49.10.4327-4334.2005
• Publication Date: 2005-09-27T16:28:08Z
• Authors: Mei Hu; Sobhan Nandi; Christopher Davies; Robert A. Nicholas
• Keywords: Neisseria gonorrhoeae; Thermus thermophilus; Ribosomal protein

ABSTRACT Neisseria gonorrhoeae becomes resistant to tetracycline by two major mechanisms: expression of a plasmid-encoded TetM protein and mutations in endogenous genes (chromosomally mediated resistance). Early studies Sparling colleagues (P. F. A. J. Sarubbi, E. Blackman, Bacteriol. 124:740-749, 1975) demonstrated that three were involved high-level chromosomally resistance (MIC ≥ 2 μg/ml): ery-2 (now referred as mtrR ), penB , tet-2 . While the identities first are known, gene has not been identified. We cloned gene, which confers resistance, from tetracycline-resistant clinical isolate N. FA6140 show is due single point mutation (Val-57 Met) rpsJ ( rpsJ1 ) encoding ribosomal S10. Moreover, identical was found six distinct isolates MIC ≥2 μg/ml. Site-saturation mutagenesis codon for Val-57 identified other amino acids (Leu Gln) conferred levels Met-57 mutation. The maps vertex loop S10 near aminoacyl-tRNA site structure 30S subunit Thermus thermophilus residue equivalent T. S10, Lys-55, within 8 9 Å bound tetracycline. These data suggest large noncharged alter rRNA tetracycline-binding site, leading lower affinity antibiotic.