Biology subjects

Unemo, M.

Publications and source records attributed to Unemo, M..

3 recordsLinked to original sources

bioRxiv2018

Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants

The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally due to the repercussions on reproductive health, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n=15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles, previously described in regard to phenotypic and reference genome characteristics, and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 901 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635, WHO_F_00745, WHO_F_01139, WHO_F_01144, and WHO_F_01226, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics databank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.

microbiology↗

bioRxiv2018

Oxford Nanopore MinION genome sequencer: performance characteristics, optimised analysis workflow, phylogenetic analysis and prediction of antimicrobial resistance in Neisseria gonorrhoeae

Antimicrobial resistant (AMR) Neisseria gonorrhoeae strains are common and compromise gonorrhoea treatment internationally. Rapid identification and characterisation of AMR gonococcal strains could ensure appropriate and even personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of the emergence and dissemination of AMR determinants that predict AMR in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that can generate bacterial genomes within one day. However, the accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench, we show that ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended therapeutic antimicrobials. We also show that the ONT-derived sequences can be useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.

genomics↗

bioRxiv2018

Antimicrobial exposure in sexual networks drives divergent evolution in modern gonococci

The sexually transmitted pathogen Neisseria gonorrhoeae is regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographic analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa as late as the 16thcentury and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted and other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multi-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks where antimicrobial treatment is frequent. A second, multi-susceptible lineage associated with heterosexual networks, where asymptomatic infection is more common, was also identified, with potential implications for infection control.

genomics↗