penA profile of Neisseria gonorrhoeae in Guangdong, China: Novel penA alleles are related to decreased susceptibility to ceftriaxone or cefixime

• Published in: International journal of antimicrobial agents Vol. 63; no. 4; p. 107101
• Main Authors: Liao, Yiwen, Xie, Qinghui, Yin, Xiaona, Li, Xiaoxiao, Xie, Junhui, Wu, Xingzhong, Tang, Sanmei, Liu, Mingjing, Zeng, Lihong, Pan, Yuying, Yang, Jianjiang, Feng, Zhanqin, Qin, Xiaolin, Zheng, Heping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2024
• Subjects: antibiotic resistance; cefixime; ceftriaxone; China; Decreased susceptibility; Extended-spectrum cephalosporins (ESCs); Infectious Disease; multilocus sequence typing; mutation; Neisseria gonorrhoeae; penA; Phylogenetic analysis; phylogeny; public health; Whole-genome sequencing; China; Decreased susceptibility; Phylogenetic analysis; Neisseria gonorrhoeae; penA; Whole-genome sequencing; Extended-spectrum cephalosporins (ESCs)
• DOI: 10.1016/j.ijantimicag.2024.107101
• ISSN: 0924-8579; 1872-7913

•Three clades with the highest prevalence of decreased susceptibility (DS) were caused by penA-60.001 or new penA alleles.•A311V and T483S are closely related to DS to cephalosporins in mosaic penA.•New alleles NEIS1753_2840 and 2837 were close to penA-60.001, with DS of 100%.•NEIS1753_2660 and 2846 displayed DS to ceftriaxone and cefixime, respectively. Resistance to extended-spectrum cephalosporins (ESCs) has become a public health concern with the spread of Neisseria gonorrhoeae and increasing antimicrobial resistance. Mutation of penA, encoding penicillin-binding protein 2, represents a mechanism of ESC resistance. This study sought to assess penA alleles and mutations associated with decreased susceptibility (DS) to ESCs in N. gonorrhoeae. In 2021, 347 gonococci were collected in Guangdong, China. Minimum inhibitory concentations (MICs) of ceftriaxone and cefixime were determined, and whole-genome sequencing and phylogenetic analysis were performed. Multi-locus sequence typing (MLST) and conventional resistance determinants such as penA, mtrR, PonA and PorB were analysed. penA was genotyped and sequence-aligned using PubMLST. Genome-wide phylogenetic analysis revealed that the prevalence of DS to ESCs was highest in Clade 11.1 (100.0%), Clade 2 (66.7%) and Clade 0 (55.7%), and the leading cause was strains with penA-60.001 or new penA alleles in clades. The penA phylogenetic tree is divided into two branches: non-mosaic penA and mosaic penA. The latter contained penA-60.001, penA-10 and penA-34. penA profile analysis indicated that A311V and T483S are closely related to DS to ESCs in mosaic penA. The new alleles NEIS1753_2840 and NEIS1753_2837 are closely related to penA-60.001, with DS to ceftriaxone and cefixime of 100%. NEIS1753_2660, a derivative of penA-10 (A486V), has increased DS to ceftriaxone. NEIS1753_2846, a derivative of penA-34.007 (G546S), has increased DS to cefixime. This study identified critical penA alleles related to elevated MICs, and trends of gonococcus-evolved mutated penA associated with DS to ESCs in Guangdong. [Display omitted]