Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Methods br Results br Discussion Persistence

    2018-11-09


    Methods
    Results
    Discussion Persistence of hyper-invasive strain types containing PorA:FetA:clonal complex associations have been described with ST-32 isolates predominantly associated with the antigenic profiles P1.7,16:F3-3 and P1.19,15:F5-1 as found here (Watkins and Maiden, 2012). Data presented here further reveals that these antigenic profiles were congruent with discrete genomic differences leading to the formation of sub-lineages which remained constant throughout all genealogical analyses (Fig. 2B and C). The Lineage 5 core genome (cgMLST) was found to contain 1,752 loci, comprising genes associated with core metabolic functions, nutrient assimilation as well as DNA metabolism, all of which are essential for the successful proliferation of meningococci in the human host. Key virulence determinants such as the purchase ABT-888 locus and genes implicated in iron acquisition were also part of the core genome. Indeed, none of the genes identified in the accessory genome encoded proteins implicated in known key cellular functions (Supplementary Table 3). Frequent recombination events between isolates from different clonal complexes have been described in core loci including 459 core genes identified by Joseph et al., many of which are implicated in amino acid, carbohydrate, nucleotide and energy metabolism as well as the biosynthesis of cofactors and vitamins (Joseph et al., 2011); the implication being that genes with a role in pathogenicity will exhibit high rates of recombination (Joseph et al., 2011; Didelot and Maiden, 2010; Hao et al., 2011). All of these genes were also part of the Lineage 5 cgMLST, 329 of which containing p-distance values equal to or below p-0.002 (Fig. 3) and including 31 loci which were identical between all of the isolates in this study (Supplementary Table 1). It has been suggested that loci involved in key metabolic functions may be subject to selection resulting in particular combinations of gene alleles affecting the ability for meningococci to transmit among carriers (transmission fitness), in turn leading to allele sets associated with clonal complexes (Buckee et al., 2008). Comparison of the 1,752 core loci resulted in cgMLST allelic profiles which clustered isolates into three distinct sub-lineages (Fig. 2B), consistent with these containing a genome-wide allelic structure. This indicates that, even over a period of four decades and across the globe, these core genes had remained conserved within this clonal complex. A total of 41 genes exhibited diversity levels comparable to many vaccine antigens (Supplementary Table 2), and many of these were outer membrane proteins and therefore subject to immune selection. However, diversity would have been expected to be associated with time, progressing over the course of the epidemic. In contrast, isolates from all four decades clustered together indicating a universal global and temporal gene pool. The identification of a star phylogeny, with sub-lineages located on short branches emanating from an internal node, is consistent with a recent population expansion originating from a founding event prior to 1969 (when the outbreak was first described). Significant phylogenetic diversification, evidenced by the much longer branches within each sub-lineage, ensued with distinct localised outbreaks, e.g. Cuba, Brazil, Norway, the United States and Chile. Taken together, these data indicate that the ST-32 serogroup B N. meningitidis pandemic had not been the result of the emergence of a single invasive “clone” followed by spread but, rather, had been the result of multiple distinct localised outbreaks. Thus, a rise in the incidence of ST-32/ET-5 meningococcal disease had possibly been the result of local host populations becoming colonised by meningococci expressing a previously unseen antigenic repertoire followed by a decline in disease several years later once host immunity had increased.