In used WGS to investigate

In , used WGS to investigate a 40-year meningococcal disease pandemic caused by the hyperinvasive ET-5/ST-32 complex. A global collection of forty-three isolates, including 14 different MLST STs, cultured from 1969 to 2008 was investigated, to set a baseline for the hyperinvasive ET-5/ST-32 complex. The researchers used a gene-by-gene approach and presented their effective pipeline to annotate the WGS data by combining the Bacterial Isolate Genome Sequence database (BIGSdb) () and the prokaryotic annotation tool (Prokka). By comparing the WGS data with closely related reference genomes, a ‘Lineage 5 pan genome’ of 1940 Manumycin A and a ‘Lineage 5 core genome’ including 1752 genes were defined. Three distinct sub-lineages based on the 1752 core loci were also described. Interestingly, most of the European and American isolates belonged to one of two related sub-lineages and these sub-lineages had diversified before the outbreaks of ST-32 in the 1970s. However, any phylogeographical analysis might be hard to evaluate in detail because isolates from Europe and North America (USA and Canada) were representing 58% of all the investigated isolates. Accordingly, it is not clear how the investigated isolates were representative and formed a baseline for the 40year global pandemic considering the low number of isolates (n=43) spanning over 40years and collected in only 20 countries. The defined pan genome included all core loci, accessory loci identified in the reference genomes, as well as loci not found in the reference genomes but found using Prokka. Interestingly, in the pan genome the researchers found a type 4 secretion system (T4SS), which has not been previously described in , and a conjugative plasmid, which most likely is consistent with horizontal genetic transfer event(s) between and . These findings further confirm the high levels of genetic exchange between species within the genus. Clearly, additional data on genomic level are crucial regarding genetic exchange between and as well as between these two pathogenic species and all commensal species, especially when both the pathogens can (pharyngeal gonorrhea is relatively common in many countries) reside in the oropharynx together with commensal species. Commensal species have also been suggested to constitute reservoirs of virulence alleles, and that they engage extensively in genetic exchange within the genus (). It would be most valuable to further elucidate many of these issues. In general, WGS provides massive amount of data to analyze and interpret, and for timely translation into clinical, epidemiological, biological and scientific relevance open-access simplified pipelines for analysis will frequently be essential. interpret the data using a genome-wide allelic profiling scheme with a standardized, effective, simple-to-use database. Some questions that come to mind are: Does this approach loose some of the resolution? Accordingly, would a genome-wide single nucleotide polymorphism (SNP) analysis/phylogeny, including and/or excluding recombination hot spot regions, give an increased resolution due to the coverage of the SNPs over the entire genome, relative stability over evolutionary time, ease of comparison, and inclusion of also intergenic regions ()? Would identical sub-lineages and phylogeny be distinguished? Would the relatedness and evolutionary distances between these be similar? Might these two different approaches contradict each other, provide the same answers and/or perhaps even supplement each other? In the future, the WGS data from hyperinvasive and additional clones in combination with transcriptomics, proteomics and appropriate genetic and phenotypic experiment have the capacity to elucidate many issues regarding evolution, virulence and general biological and transmission fitness of lineages. Furthermore, novel targets for diagnostics, antimicrobials and vaccines will be identified and antigenic diversification of vaccine candidates over time and national and global transmission of hyperinvasive meningococcal lineages can be adequately monitored.