Biology subjects

Osnes, M. N.

Publications and source records attributed to Osnes, M. N..

3 recordsLinked to original sources

bioRxiv2023

The inter-continental population dynamics of Neisseria gonorrhoeae

Neisseria gonorrhoeae is a globally distributed sexually transmitted bacterial pathogen. Recent studies have revealed that its evolution has been shaped by antibiotic use, while molecular surveillance efforts have demonstrated large changes in lineage composition over relatively short time-spans. However, the global population dynamics of N. gonorrhoeae remain unsatisfyingly characterized. To reconstruct recent large-scale population dynamics, we generated a dated phylogeny from 9,732 N. gonorrhoeae genomes and found the effective population size of the species to have expanded gradually over the past two centuries. While the effective population size of clades with reduced susceptibility to extended-spectrum cephalosporins started declining around 2010, a major clade containing a mosaic mtr operon associated with cephalosporin susceptibility and decreased azithromycin did not display any reduction in population size. Using ancestral trait reconstruction analyses, we delineated transmission lineages, defined as groups of sequences in which all the samples can be traced back to the same import event to a given location. Import, export and local transmission dynamics across two densely sampled locations (Norway and Victoria, Australia) were investigated in detail. Norway exhibited substantially higher rates of strain import and export compared to Victoria, where incidence was to a larger extent fuelled by locally transmitted lineages. Taken together, our work highlights the power of large-scale phylogenomic analyses to uncover the complex dynamics of lineage transmission in N. gonorrhoeae.

microbiology↗

bioRxiv2020

High-frequency switching between ON and OFF states in the phase variable modB methylase impacts gonococcal azithromycin susceptibility

The gonococcal adenine methylases modA and modB, belonging to separate Type III restriction modification systems, are phase variable and could thus enable rapid adaptation to changing environments. However, the frequency of phase variation across transmission chains and the phenotypic impact of phase variation are largely unknown. Here we show that the repeat tracts enabling phase variation expand and contract at high rates in both modA and modB. For modB, multiple ON/OFF transition events were identified over the course of a single outbreak. A mixed effects model using population samples from Norway and a global meta-analysis collection indicates that modB in the OFF state is predictive of moderately decreased ceftriaxone susceptibility. Our findings suggest that modB orchestration of genome-wide 6-methyladenine modification controls the expression of genes modulating ceftriaxone susceptibility. ImportanceDespite significant progress, our current understanding of the genetic basis of antibiotic susceptibility remains incomplete. The gonococcal methylase modB is phase variable, meaning that it can be switched ON or OFF via contraction or expansion of a repeat tract in the gene during replication. We find that transitions between the ON and OFF state occur at high frequency. Furthermore, isolates harbouring modB in a configuration predicted to be inactive had decreased susceptibility to ceftriaxone, an antibiotic used to treat gonorrhea. This finding improves understanding of the genetic underpinnings of antibiotic resistance, but further work is needed to elucidate the mechanics and broader phenotypic effects of epigenetic modifications and transcription.

microbiology↗

bioRxiv2020

The sudden emergence of a Neisseria gonorrhoeae strain with reduced susceptibility to extended-spectrum cephalosporins, Norway

The Neisseria gonorrhoeae multilocus sequence type (ST) 7827 emerged in dramatic fashion in Norway in the period 2016-2018. Here, we aim to determine what enabled it to establish and spread so quickly. In Norway, ST-7827 isolates were almost exclusively isolated from men. Phylogeographic analyses demonstrated an Asian origin of the ST with multiple importation events to Europe. The ST was uniformly resistant to fluoroquinolones and associated with reduced susceptibility to both azithromycin and the extended-spectrum cephalosporins (ESC) cefixime and ceftriaxone. We identified additional independent events of acquisition of penA and porB alleles in Europe, associated with further reduction in cefixime and ceftriaxone susceptibility, respectively. Transmission of the ST was largely curbed in Norway in 2019, but our results indicate the existence of a reservoir in Europe. The worrisome drug resistance profile and rapid emergence of ST-7827 calls for close monitoring of the situation.

genomics↗