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Vol 48(2014) N 6 p. 858-863; DOI 10.1134/S0026893314060119 Full Text

A.A. Kubanova, A.A. Kubanov, O.S. Kozhushnaya, D.V. Vorob'ev*, V.S. Solomka, N.V. Frigo**

The role of some individual amino acid substitutions in penicillin-binding protein (PBP2) of Neisseria gonorrhoeae in the emergence of resistance to ceftriaxone

State Research Center of Dermatovenerology and Cosmetology, Ministry of Healthcare of the Russian Federation, Moscow, 107076 Russia

*v.denis083@gmail.com
**frigo@cnikvi.ru
Received - 2014-03-06; Accepted - 2014-05-28

The study was aimed at identifying amino acid replacements in the structure of penicillin-binding PBP2 protein, which may influence on the development of resistance of N. gonorrhoeae to third-generation cephalosporins. For this purpose, the penA gene, which encodes the protein, was sequenced for 50 strains of N. gonorrhoeae, including 20 strains with high sensitivity to ceftriaxone (MIC, Minimum Inhibitory Concentration, is 0.002 mg/L) and 30 strains with decreased sensitivity to ceftriaxone (MIC = 0.03 - 0.25 mg/L). The MICs of the strains with high sensitivity were 30 - 250 times higher than that of the strains with decreased sensitivity. Then, the amino acid sequence of the PBP2 protein obtained based on the nucleotide sequence of this gene was analyzed. Mutations in the penA gene and amino acid substitutions in the PBP2 protein were found in 16 of 20 strains (80%) with high sensitivity to ceftriaxone and in all strains with decreased sensitivity to ceftriaxone. Amino acid replacements in the PBP2 protein were compared with amino acid replacements in the groups that characterize the structure of PBP2 in accordance with the international classification Ito M. The amino acid replacement of PBP2 at positions 346, 505, 511,517, 543, 567, 575, 576 are associated with V group by Ito M and have features of resistance of N. gonorrhoeae to ceftriaxone authentically (OR = 3.9 ± 2.5; χ2 = 4.9; p < 0.05). It was shown that the replacement of glycine to serine at position 543 of PBP2 in the analyzed strains induced the multiple increase of resistance to ceftriaxone. These data indicate the significance of amino acid substitutions at positions 346, 505, 511, 517, 567, 575 and, in particular, 543 for development of resistance of N. gonorrhoeae strains to ceftriaxone.

gonococci, Neisseria gonorrhoeae, penA gene, penicillin-binding PBP2 protein, ceftriaxone, antibiotic resistance



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