Genomic diversity and antimicrobial resistance determinants among publicly available M ycoplasma genitalium genomes: a comparative phylogenomic analysis

Background Antimicrobial resistance is increasingly challenging the clinical management of Mycoplasma genitalium infections. This study aimed to characterize the genomic diversity, population structure, molecular typing profiles, and distribution of antimicrobial resistance-associated determinants among publicly available M. genitalium genomes. Methods All 64 M. genitalium genomes publicly available in NCBI and PubMLST at the time of data collection were included. Genomes were characterized by mgpB and MG309 molecular typing and screened for mutations associated with macrolide and fluoroquinolone resistance. Phylogenetic relationships were investigated using a recombination-filtered core-genome alignment, and molecular typing and antimicrobial resistance profiles were mapped onto the resulting maximum-likelihood phylogeny. Results Substantial molecular diversity was observed, with 29 mgpB and 21 MG309 types identified. Macrolide resistance-associated 23S rRNA mutations were detected in 34/64 (53%) genomes. The fluoroquinolone resistance-associated ParC substitutions S83I and S83 R were detected in 14 (22%) and one genome, respectively. Relevant GyrA substitutions were less frequent and occurred exclusively in genomes also carrying ParC S83I. Overall, 15/64 (23%) genomes exhibited a dual-resistance genotype, whereas 19/64 (30%) carried macrolide resistance-associated mutations without concomitant fluoroquinolone resistance markers. Resistance-associated genotypes occurred across multiple phylogenetically distinct genomic backgrounds, while clusters of closely related isolates sharing molecular typing and resistance profiles were also identified. Conventional mgpB and MG309 typing did not consistently recapitulate whole-genome phylogenetic relationships. Conclusions These findings reveal substantial genomic diversity and a high frequency of resistance-associated determinants among publicly available M. genitalium genomes, supporting the expansion of geographically representative genomic surveillance to monitor the emergence and dissemination of antimicrobial resistance.