Abstract
In March 2026, an unusually large outbreak of invasive meningococcal disease (IMD) in Kent, UK, was linked to attendance at one nightclub over a single weekend. The outbreak organism was a Neisseria meningitidis variant belonging to the longstanding hyperinvasive genotype, cc41/44. Using genome analysis of six isolates from patients, alongside >48,000 meningococcal genomes, we investigated whether the outbreak variant had acquired traits potentially contributing to the highly invasive phenotype. The six isolates were capsular group B, sequence type (ST-)485, and essentially indistinguishable, consistent with the focal nature of the outbreak. Compared with their closest available relatives, we found changes mediated by phase variation, nucleotide variation, and horizontal gene transfer (HGT) involving adhesins, iron-acquisition systems (including Transferrin and Lactoferrin binding proteins, and FetA), and Type IV pili (Tfp), factors which affect bacteria-bacteria and bacteria-host interactions. These changes occurred in a ST-485 sub-lineage that expressed capsule at high levels and a PorA porin with a truncated surface-exposed epitope, both of which are predicted to reduce immune recognition. Donors for the HGT events were predominantly carriage-associated N. meningitidis and Neisseria cinerea. We show that meningococcal variants responsible for previous focal outbreaks have not been seen subsequently. We propose that focal outbreaks of IMD are caused by meningococcal variants that may have acquired traits from non- or less invasive organisms, but subsequently these variants disappear, as their highly invasive phenotype is inconsistent with sustained transmission. Ongoing disease surveillance alongside carriage studies are therefore essential to inform public health risk and manage epidemic IMD.
Competing Interest Statement
CMT and RME are inventors on patents for meningococcal vaccines. JPD is a co-founder and Director of Immunosig Ltd, a company which offers antigen microarray-based services. JL, RB, SAC and XB perform contract research on behalf of UKHSA for GSK, Pfizer, Sanofi and Serum Institute of India.
Funder Information Declared
Wellcome Trust, https://ror.org/029chgv08, 218205/Z/19/Z, 221924/Z/20/Z
NIH Common Fund, https://ror.org/001d55x84, R01AI127793
Source:
Link: https://doi.org/10.64898/2026.09.17.752363
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