Exploring genomic and phenotypic differences in Neisseria meningitidis : understanding carriage and invasive disease

• Neisseria meningitidis can colonise the nasopharynx in humans and is also the cause of invasive meningococcal disease (IMD), which often presents as septicaemia and meningitis with high mortality rates. Invasive disease is often associated with specific capsular serogroups and clonal complexes (CC). In Sweden, serogroups Y and W have had a high incidence in recent years, but were previously considered rare causes of IMD, suggesting a change in the virulence potential of these serogroups. Currently, no specific genes exist that can reliably predict whether an N. meningitidis isolate will result in invasive disease or remain in the carriage state. Genetically similar isolates can be found during carriage and IMD, and it is more common for the carriage isolates to lack a capsule. The aim of this thesis was to investigate how genetic and phenotypic differences in N. meningitidis, can affect the virulence and the transition from a carriage state to invasive disease.The results indicate that the increase of serogroup W in Sweden is due to a specific lineage of CC11. This CC is rarely found among carriers and is considered highly virulent. Infections in transgenic mice with serogroup W CC11 isolates showed a greater virulence compared to serogroup Y isolates from other CCs. Although both serogroups are common causes of IMD in Sweden, they differ in virulence in transgenic mice. A genome-wide association study comparing carriage and invasive isolates, revealed that there were genetic variants in genes associated with virulence between these isolates. Among these variants were pilE/pilS, which are involved in the type IV pili. Comparison of pilE gene expression between carriage and invasive isolates showed no significant difference between these isolates. However, a difference in the class of the PilE protein was found between invasive and carriage isolates. Further research is needed to understand the impact of these genetic variations on the transition from carriage to invasive disease, also considering how factors in the human host and the environment that may contribute to the development of invasive disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

Nyckelord

Neisseria meningitidis

invasive meningococcal disease

carriage

virulence

whole genome sequencing

genome wide association study

Publikations- och innehållstyp

vet (ämneskategori)

dok (ämneskategori)