Comparison of Phenotypic and Genotypic Approaches to Capsule Typing Neisseria meningitidis Using Invasive and Carriage Isolate Collections.

Jones CH1, Mohamed N2, Rojas E2, Andrew L2, Hoyos J2, Hawkins JC2, McNeil LK2, Jiang Q2, Mayer LW3, Wang X3, Gilca R4, De Wals P4, Pedneault L2,Eiden J2, Jansen KU2, Anderson AS2.

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Abstract

Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitidis; however, as opposed to the disease state, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity. Two vaccines are now licensed for the prevention of MnB disease; an additional possible benefit of these vaccines could be to indirectly protect against disease by disrupting nasopharyngeal carriage, e.g. herd protection. To investigate this potential, accurate diagnostic approaches are required to characterize MnB carriage isolates. In contrast to invasive meningococcal disease (IMD) isolates that can readily be serogrouped, carriage isolates often lack capsule expression making standard phenotypic assays untenable for strain characterization. Several antibody based methods were evaluated for their ability to serogroup isolates and compared to two genotyping methods (real-time PCR (rt-PCR) and whole genome sequencing (WGS) to identify which approach might most accurately ascertain the polysaccharide group associated with carriage isolates. WGS and rt-PCR were in agreement for 99% of IMD isolates, including those carrying coding sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly identified serogroups for between 69 and 98% of IMD isolates. In contrast, only 47% of carriage isolates were groupable by genotypic methods due to mutations within the capsule operon, and of the isolates identified by genotypic methods, ≤43% were serogroupable by any of the phenotypic methods tested. These observations highlight the difficulties in serogrouping and capsular genogrouping meningococcal carriage isolates. Based on our findings, WGS is the most suitable approach for the characterization of meningococcal carriage isolates.