Research Article: Genomic analysis of Neisseria meningitidis carriage isolates during an outbreak of serogroup C clonal complex 11, Tuscany, Italy

Date Published: May 28, 2019

Publisher: Public Library of Science

Author(s): Luigina Ambrosio, Arianna Neri, Cecilia Fazio, Gian Maria Rossolini, Paola Vacca, Eleonora Riccobono, Fabio Voller, Alessandro Miglietta, Paola Stefanelli, Daniela Flavia Hozbor.


In 2015–2016, a cross-sectional carriage survey was performed in Tuscany Region, Italy, during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C clonal complex 11 (MenC:cc11). This study aims to evaluate the genomic profile of meningococcal carriage isolates collected during the survey.

Whole-genome sequencing (WGS) was performed using Illumina MiSeq on 85 cultivated meningococcal carriage isolates received at the Dept. of Infectious Disease, National Institute of Health (Istituto Superiore di Sanità, ISS), as National Reference Laboratory (NRL) for Invasive Meningococcal Disease (IMD). De novo assembled genomes were scanned by the BIGSdb platform to assign: the genotypic profiles, the cgMLST, the vaccine antigen variants and allele types of antimicrobial resistance associated genes, together with denitrification pathway loci.

Capsule null and non-groupable meningococci accounted for 52.9% and 10.6%, respectively. Among the remaining carriage isolates, serogroup B was the predominant (71.0%). Serogroup C meningococci were culture negative and unavailable for WGS. Overall, 64 genotypic profiles were identified and, based on cgMLST, isolates clustered according to clonal complexes. Eight isolates (9.4%) harbored at least one gene encoding a 4CMenB vaccine antigen. Mutated penA alleles were found in more than 82%. Finally, complete aniA and norB coding sequences were detected among 71.8% of carriage isolates.

Meningococcal carriage isolates collected during the MenC:cc11 outbreak were characterized by an extensive genetic diversity. The lack of outbreak-related isolates among carriage might be attributable to the high transmissibility with low duration of colonization of MenC:cc11 meningococci.

Partial Text

Neisseria meningitidis (also known as meningococcus) can be considered a common commensal bacterium of the human pharynx, which represents its natural reservoir [1]. Pharyngeal carriage prevalence is age related, increasing through adolescence [2]. Occasionally, meningococci can invade the bloodstream and other normally sterile sites, leading to invasive meningococcal disease (IMD), whose most frequent clinical presentations are sepsis and meningitis.

As shown in Table 1, 52.9% (45/85) carriage isolates were capsule null (cnl) and 10.6% (9/85) non-groupable (NG). The remaining 36.5% (31/85) displayed a complete capsule locus (cps): 22 were B (MenB 71.0%; 22/31), 7 Y (MenY 22.6%; 7/31), 1 E (MenE 3.2%; 1/31) and 1 Z (MenZ 3.2%; 1/31). The analysis of allelic variants within the capsule locus revealed that 9 MenB, 6 MenY and the unique MenZ harbored intact coding sequences in the cps locus, while the remaining isolates presented premature stop codons in one or more cps genes that would result in the loss of encapsulation. No meningococcal C (MenC) isolates among the samples were cultivated during the survey.

Since 2012, a significant increase in the proportion of MenC cases has been observed in Italy, making it one of the most frequent serogroups causing IMD in the country [23].




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