Genomic and evolutionary insights into a novel Neisseria meningitidis genogroup W clonal complex 11 variant with dual resistance to penicillin and azithromycin in Spain.
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Roca-Grande Josep, Moreno-Mingorance Albert, Álvarez-López Patricia, Arando Maider, Bellés-Bellés Alba, Calvo-Montes Jorge, Càmara Jordi, Cercenado Emilia, Descalzo Vicente, Galán-Ladero M Ángeles, García-Pérez Jorge Néstor, Gómez Frederic, Hoyos-Mallecot Yannick, López-Madueño Joan, Lung Mayli, Martín-Nalda Andrea, Mir-Cros Alba, Muñoz-Almagro Carmen, Navarro de la Cruz Daniel, Oliveira-Souto Inés, Orellana M Ángeles, Palop Begoña, Pérez-Argüello Amaresh, Pérez-Moreno Mar Olga, Puigsech-Boixeda Guillem, Quesada M Dolores, Rivera Alba, Rodrigo Carlos, Rodriguez-Fernandez Ana, Ruiz de Gopegui Enrique, Sarvisé Carolina, Serre-Delcor Núria, Soler-Palacín Pere, Soler-Garcia Aleix, Trejo-Zahínos Jesús, Viñado Belén, Larrosa M Nieves, González-López Juan José
Аннотация
Neisseria meningitidis clonal complex 11 (cc11) is a hyperinvasive lineage associated with global dissemination and outbreaks, including the 'South American/UK' sublineage. In Spain, cc11 serogroup W cases have increased in recent years; however, the evolutionary dynamics of circulating variants remain insufficiently characterized. This study aimed to assess the clonal diversity, temporal evolution and antimicrobial resistance profiles of cc11 isolates recovered in Spain between 2011 and 2025. A total of 1,226 isolates (406 invasive and 820 non-invasive) were collected across 8 Spanish regions, from which cc11 isolates were selected for analysis. Whole-genome sequencing (WGS) was used to perform core-genome multilocus sequence typing and SNP-based Bayesian phylogenetics to characterize population structure. Antimicrobial susceptibility was assessed using gradient diffusion, and genetic determinants of resistance were identified by WGS. We identified 179 cc11 isolates, mostly belonging to genogroup W (73.7%) and lineage 11.1 (85.5%). The 'South American/UK' sublineage was the main sublineage and displayed extensive diversification. A previously undescribed variant, designated the '2020 strain', emerged with an estimated most recent common ancestor in 2017 and accounted for 77.2% of 'South American/UK' sublineage isolates recovered between 2023 and 2025. This variant was mainly identified in respiratory samples from men who have sex with men but was also associated with invasive meningococcal disease in other population groups. The '2020 strain' exhibited resistance to penicillin and azithromycin, likely driven by penicillin-binding protein 2 and MtrCDE alterations. The emergence of this antimicrobial-resistant variant highlights the adaptive capacity of cc11 and the importance of genomic surveillance to monitor its evolution and public health relevance.