Reconstruction of Dispersal Patterns of Hypervirulent Meningococcal Strains of Serogroup C:cc11 by Phylogenomic Time Trees

Neisseria meningitidis is one of the few commensal bacteria that can even cause large epidemics of invasive meningococcal disease (IMD). N. meningitis serogroup C belonging to the hypervirulent clonal complex 11 (cc11) represents an important public health threat worldwide. We reconstructed the dispersal patterns of hypervirulent meningococcal strains of serogroup C:cc11 by phylogenomic time trees. In particular, we focused the attention on the epidemic dynamics of C:P1.5.1,10-8:F3-6;ST-11(cc11) meningococci causing outbreaks, as occurred in the Tuscany region, Italy, in 2015 to 2016. A phylogeographic analysis was performed through a Bayesian method on 103 Italian and 208 foreign meningococcal genomes. The C:P1.5.1,10-8:F3-6;ST-11(cc11) genotype dated back to 1995 (1992 to 1998) in the United Kingdom. Two main clades of the hypervirulent genotype were identified in Italy. The Tuscany outbreak isolates were included in different clusters in a specific subclade which originated in the United Kingdom around 2011 and was introduced in Tuscany in 2013 to 2014. In this work, phylogeographic analysis allowed the identification of multiple introductions of these strains in several European countries and connections with extra-European areas. Whole-genome sequencing (WGS) combined with phylogeography enables us to track the dissemination of meningococci and their transmission. The C:P1.5.1,10-8:F3-6;ST-11(cc11) genotype analysis revealed how a hypervirulent strain may be introduced in previously naive areas, causing a large and long-lasting outbreak.