Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins

Abstract

The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 μg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 μg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu → Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC ≥ 0.125 μg/mL) was observed for these four genes. Of the 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC ≥ 0.125 μg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance.

Differences inNeisseria gonorrhoeaepopulation structure and antimicrobial resistance pattern between men who have sex with men and heterosexuals

“…The fact that in our study G1407 was the most prevalent in the heterosexual population, which at the same time were infected by more resistant strains, reinforces our previous findings [18], in which G1407 was clearly related with decreased susceptibility to the extended spectrum cephalosporins, and G2992 with susceptible strains. This could explain why the strains infecting heterosexual patients in our area are more resistant than those infecting MSM, likely because cluster G1407 is circulating in the heterosexual population and it is known that this genogroup develops resistance with greater frequency [18]. Few studies in Europe have explored the distribution of N. gonorrhoeae strains in populations with different sexual orientations [5,8,9,19]; the majority of these were done in the UK [8] and Holland [5,19,20], but to date not in Spain.…”

Epidemiology, molecular characterisation and antimicrobial susceptibility ofNeisseria gonorrhoeaeisolates in Madrid, Spain, in 2016

“…Comparing with other Spanish regions, Serra-Pladevall et al . [25] reported a cefixime resistance rate of 8.2% among gonococcal isolates during 2013 in Barcelona and 0.6% resistance to ceftriaxone. Likewise, Cobo et al .…”

Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness

“…Three mutations (A501R, A501V, and A501T) comprised 90% of the sequenced clones and were obtained with similar frequency, whereas two other mutations, A501S and A501P, were isolated at much lower frequencies. The identification of three of these mutations (A501V, A501T, and A501P) was expected, as these mutations have been observed in either non-mosaic penA alleles from strains with decreased susceptibility to cephalosporins (A501V and A501T) (13, 28–31) , or in a mosaic penA allele from ceftriaxone-resistant strains (A501P) (17, 18) . The isolation of just one A501P mutation in our screen was surprising given its prior emergence in the penA alleles of the ceftriaxone-resistant F89 (17) and the Spanish gonococcal isolates (18) .…”