Mycoplasma genitalium: whole genome sequence analysis, recombination and population structure

Abstract

BackgroundAlthough Mycoplasma genitalium is a common sexually transmitted pathogen causing clinically distinct diseases both in male and females, few genomes have been sequenced up to now, due mainly to its fastidious nature and slow growth. Hence, we lack a robust phylogenetic framework to provide insights into the population structure of the species. Currently our understanding of the nature and diversity of M. genitalium relies on molecular tests targeting specific genes or regions of the genome and knowledge is limited by a general under-testing internationally. This is set against a background of drug resistance whereby M. genitalium has developed resistance to mainly all therapeutic antimicrobials.ResultsWe sequenced 28 genomes of Mycoplasma genitalium from temporally (1980–2010) and geographically (Europe, Japan, Australia) diverse sources. All the strain showed essentially the same genomic content without any accessory regions found. However, we identified extensive recombination across their genomes with a total of 25 regions showing heightened levels of SNP density. These regions include the MgPar loci, associated with host interactions, as well as other genes that could also be involved in this role. Using these data, we generated a robust phylogeny which shows that there are two main clades with differing degrees of genomic variability. SNPs found in region V of 23S rRNA and parC were consistent with azithromycin/erythromycin and fluoroquinolone resistances, respectively, and with their phenotypic MIC data.ConclusionsThe sequence data here generated is essential for designing rational approaches to type and track Mycoplasma genitalium as antibiotic resistance increases. It represents a first approach to its population genetics to better appreciate the role of this organism as a sexually transmitted pathogen.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4399-6) contains supplementary material, which is available to authorized users.

Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genitalMycoplasma genitaliuminfection

“…However, WGS for MG has not yet been validated for phylogenetic analysis, with concerns raised about degrees of genome recombination. 29 Using DLST, we identified two major strain lineages, as well as detected an increase in MG2 proportion post-MDA. This shift might have occurred due to differences in characteristics of infection such as bacterial load, leading to variable antibiotic susceptibility, 30 which may introduce sequencing bias.…”

Evaluation of the ResistancePlus MG FleXible Assay for Detection of Wild-Type and 23S rRNA-Mutated Mycoplasma genitalium Strains

“…The RPMG Flex assay showed no cross-reaction to other phylogenetically related or nontarget organisms (Table 2), including in the presence of Mycoplasma pneumoniae, the closest relative of M. genitalium, at 1 ϫ 10 6 genomes/ml (20). Confidence in the performance of the assay was further boosted when no interference to detection of M. genitalium or 23S rRNA mutations was evident in the presence of potentially interfering substances (Table 3).…”

Sequence variation and immunogenicity of the Mycoplasma genitalium MgpB and MgpC adherence proteins during persistent infection of men with non-gonococcal urethritis

“…However, each of these previous studies assessed a limited number of sequences (5 to 18 cloned sequences per specimen) and only one or two variable regions in these patients. Fookes et al [50] assessed changes in the entire mgpBC operon by whole genome sequencing of isolates obtained 79 days apart, however, as single colony cloned strains were sequenced, the full breadth of variation within the infecting population could not be assessed. Our study provides a comprehensive assessment of variation across all variable regions in both MgpB and MgpC in men who were each persistently infected with a single strain.…”