Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis.

Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in Neisseria meningitidis and reduced susceptibility to third-generation cephalosporines (3GC) and the rare acquisition of ROB-1 beta-lactamase were also described. Modifications of penicillin-binding protein 2 (PBP2) encoded by the penA gene are the main described mechanism for the reduced susceptibility to penicillin and to other beta-lactams. penA modifications were analyzed using the sequences of all penA genes from cultured isolates between 2017-2021 in France (n = 1255). Data showed an increasing trend of reduced susceptibility to penicillin from 36% in 2017 to 58% in 2021. Reduced susceptibility to 3GC remained limited at 2.4%. We identified 74 different penA alleles and penA1 was the most frequent wild-type allele and represented 29% of all alleles while penA9 was the most frequently altered allele and represented 17% of all alleles. Reduced susceptibility to 3GC was associated with the penA327 allele. The amino acid sequences of wild-type and altered PBP2 were modeled. The critical amino acid substitutions were shown to change access to the active S310 residue and hence hinder the binding of beta-lactams to the active site of PBP2.

Neisseria meningitidis Antimicrobial Resistance in Italy, 2006 to 2016.

The aim of this study was to evaluate the antimicrobial susceptibilities of 866 Neisseria meningitidis invasive strains during 11 years of surveillance in Italy. Two and six strains were resistant to ciprofloxacin and rifampin, respectively. Forty-five percent were penicillin intermediate, associated with hypervirulent serogroup C clonal complex 11. All of the strains were susceptible to cephalosporins.

Cooperative Recognition of Internationally Disseminated Ceftriaxone-Resistant Neisseria gonorrhoeae Strain.

Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.

Roles of penA and mtrR gene mutations in in vitro-induced resistance of Neisseria gonorrhoeae to ceftriaxone / 中华皮肤科杂志

Objective To investigate the roles of penA and mtrR gene mutations in resistance of Neisseria gonorrhoeae to ceftriaxone.Methods Standard strains of Neisseria gonorrhoeae (ATCC-49226),clinical strains of Neisseria gonorrhoeae with high sensitivity to ceftriaxone (2012-4052 and 2012-15361) and clinical strains of Neisseria gonorrhoeae with reduced sensitivity to ceftriaxone (2012-5616) were treated with ceftriaxone at subinhibitory concentration (50％ MIC),so as to induce the resistance to ceftriaxone.DNA was extracted from the primary strains before the treatment and daughter strains resistant to ceftriaxone after the treatment,followed by the amplification and DNA sequencing of the penA and mtrR genes.Results For strains 2012-5616 and ATCC-49226,ceftriaxone-resistant strains with MIC ≥ 1 mg/L were obtained after 26 and 28 passages,respectively.For strains 2012-4052 and 2012-15361,ceftriaxone-resistant strains with MIC ≥ 0.5 mg/L were obtained after 22 and 36 passages,respectively.Sequence analysis of the penA gene revealed that A501T and G542S mutations were identified in the induced resistant ATCC-49226 strains,but no new mutations were observed in the other 3 strains.All the 4 mutant strains showed penicillin-binding protein 2 (PBP2) of gene sequence type ⅩⅧ and no mosaic structure of the penA gene was found in the strains.Sequence analysis of the mtrR gene showed that the A39T mutation was found in the 2012-5616 and ATCC-49226 strains before and after the induction,as well as in the coding region of the mtrR gene in the induced resistant 2012-4052 strains.Conclusion The A501T and G542S mutations in the penA gene and A39T mutation in the mtrR gene may play a role in the resistance of Neisseria gonorrhoeae to ceftriaxone.