Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch.

Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis.

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African 'meningitis belt' and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.

Molecular characterization of invasive Neisseria meningitidis strains isolated in Chile during 2010-2011.

BACKGROUND: With the upcoming licensure of Outer Membrane Protein-based vaccines against meningococcal disease, data on disease incidence and molecular characteristic of circulating N. meningitidis strains in Latin American countries is needed. Chile is, to date, one of the few countries in the region that has performed this type of work in a comprehensive collection of disease-associated strains from two consecutive years, 2010-2011. METHODS: A total of 119 N. meningitidis strains isolated from patients with invasive disease in Chile in 2010-2011 were characterized by the National Reference Laboratory. Serogroup determination, MLST and porA typing were performed. RESULTS: Serogroup B was predominant in both study years, but W135 experienced a noticeable increase in 2011 compared to 2010. ST-11 complex, ST-41/44 complex ST-32 complex were the most prevalent among the isolates, and were strongly associated with serogroups W135 (ST-11 Complex) and B (ST-41/44 and ST-32 complexes). Likewise, the major porA types detected were strongly associated with these three clonal complexes: P1.5,2 was found exclusively among W135:ST-11 isolates, whereas P1.7, 2-3 was only detected in C:ST-11. ST-41/44 isolates mainly had P1.10-8, and ST-32 complex were associated with a P1.18-8 porA. CONCLUSIONS: Our data show disease-associated N. meningitidis circulating in Chile are similar to those found in other parts of the world. The increase on W135:ST-11 isolates observed in 2011 foretold the unusual epidemiological situation experienced in the country in 2012, and MLST data show that this strain is indistinguishable from the one linked to the global Hajj 2000-related outbreak that occurred in 2001. Finally, this work demonstrates the importance of maintaining a strong national surveillance program integrating clinical, epidemiological and laboratory data and incorporating gold standard diagnostic and characterization techniques that allow the data to be compared all over the world.