• 2018-07
  • 2018-10
  • 2018-11
  • fructose 1 6 bisphosphatase Outside the meningitis belt sero


    Outside the meningitis belt, serogroup W strains accounted for 62% of all invasive meningococcal disease strains in South Africa in 2005 compared to 5% in 2000, with 93% of W strains belonging to ST-11 lineage (Mothibeli et al., 2011). Our study reveals that 71·4% of 98 South African W ST-11 strains from 2003 to 2013 belonged to the Hajj cluster. These results are consistent with the finding that 85% of invasive W ST-11 strains isolated in South Africa in 2005 had the Hajj-related fHbp allele 9 (Mothibeli et al., 2011). Taken together, these data show that the Hajj cluster strains were predominant in South Africa. In the UK, Hajj related W ST-11 strains predominated in 2000–2004 but were replaced by endemic non Hajj strains thereafter (Valenzuela et al., 2013). Likewise, our results suggest that the small case clusters of W ST-11 in the United States 2008–2009 (Doyle et al., 2010), and larger clusters in south Brazil 2003–2005 (Lemos et al., 2010), and Chile 2010–2012 (Barra et al., 2013) represent the local spread of endemic strains with no evidence of direct spread of the Hajj clone. 16S ribosomal RNA gene sequencing was previously the most discriminatory test for differentiating the Hajj clone, which exhibited 16S type 31 compared to type 13 and 14 in sporadic W ST-11 strains (Mayer et al., 2002), However, our data demonstrate that some strains linked to the Hajj outbreak contained novel 16S alleles. There are several hypotheses that could explain the emergence of the Hajj fructose 1 6 bisphosphatase and subsequent W ST-11 outbreaks worldwide (Kelly and Pollard, 2003). FHbp is a major meningococcal antigen and a virulence determinant that is a component of vaccines developed for protection against serogroup B strains. The introduction of a novel FHbp antigenic type into an immunologically naïve population may have played a part in the emergence of the Hajj clone. In support of this hypothesis, the fHbp allele 9 unique to the Hajj related strains, belongs to variant group 1/sub-family B and has limited immunologic cross reactivity with variant groups 2 and 3/sub-family A, which were prevalent among Cluster 2 strains (Granoff, 2010; Beernink et al., 2009). Similarly, antigenic shift was associated with increases in serogroup C and serogroup Y meningococcal disease in the U.S. in the 1990s (Harrison et al., 2006). Alternatively, the genomic changes we observed in the Hajj clone may be associated with increased virulence. For example, the nitrite reductase (aniA) gene — encoding a major outer membrane copper-containing protein, and the nitric oxide reductase (nor, sometimes referred to as norB) gene are both essential for overcoming oxidative stress and resistance to phagocytic lysis by macrophages (Anjum et al., 2002). Also, N. meningitidis lacking the nor gene have been shown to survive poorly in human nasopharyngeal tissue (Stevanin et al., 2005). Together, these data suggest that allelic variation in key virulence determinants may have a potential contribution to W ST-11 emergence. Then again, the genomic events (allelic exchange within fHbp, nor and aniA) observed could simply be markers of other, unidentified, genomic events that lead to changing epidemiologic behavior of W ST-11. This study provides increasing evidence on the role of recombination in the emergence and persistence of meningococcal lineages and demonstrates the role of recombinant gene alleles in molecular epidemiologic typing of meningococcal isolates. We also add to the body of evidence showing the suitability of fHbp gene sequencing for routine meningococcal surveillance (Toros et al., 2014). A limitation of this study is incomplete data as a result of variations in meningococcal disease surveillance by country and over the study period particularly in the 1970s-1990s. Historically, a large majority of ST-11 strains expressed serogroup C capsule with a significant minority of isolates expressing both B and W capsules. On the Neisseria PubMLST database (, 78% of 665 ST-11 strains isolated in 1960–1999 expressed C capsule, while serogroups B and W each accounted for 10.4% of strains in the same period. Although our data suggest that the W ST-11 lineage diverged from an ancestral serogroup C ST-11 strain, the possibility that W ST-11 arose fructose 1 6 bisphosphatase from another serogroup cannot be ruled out.