Open Access Te Herenga Waka-Victoria University of Wellington
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Identification of a meningococcal adhesin that inhibits epithelial cell migration

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posted on 2021-12-08, 14:43 authored by Gabrielle Greig

Neisseria meningitidis virulence is polygenic, therefore comparing many genomes may not yield strictly disease-associated virulence factors. An alternative approach is comparing closely related isolates, such as those from household contacts. Disease isolates have been shown to inhibit epithelial cell wound repair, while many carriage isolates do not. In this study, bacteria collected from disease patients and healthy household contacts were compared to identify the meningococcal factor responsible for wound repair inhibition and investigate how it contributes to invasive disease. Host cell wound repair inhibition was compared between disease-associated meningococcal isolate, NZ97/052, and isolates NZCM111 and NZCM112, from asymptomatic household contacts. Migrating bronchial airway cells were infected with meningococcal isolates and wound closure was evaluated by microscopy. NZ97/052 and NZCM111 both inhibited wound repair, whereas NZCM112 did not. To investigate if this was due to bacterial consumption of an important nutrient, infected cells were supplemented with nutrients known to be important for meningococcal growth and cell migration. Iron supplementation resulted in carriage associated isolates gaining the ability to inhibit wound repair. Genome and transcriptome comparisons were completed between NZ97/052 and NZCM112, which differ in wound repair inhibition. This analysis identified a frameshift mutation in NZCM112 in the haptoglobin-haemoglobin utilization gene, hpuA, which caused complete loss of expression. The hpuA gene was deleted by allelic replacement from NZ97/052, nullifying its ability to inhibit host cell migration. Furthermore, bacterial association and fluorescence microscopy assays suggested that HpuA contributes to meningococcal attachment to bronchial epithelial cells, as the hpuA mutant had significantly lower cell association. Heterologous expression of HpuA in E. coli resulted in higher levels of cell association, indicating that HpuA is sufficient to mediate bacterial adhesion to human bronchial epithelial cells. This work reveals novel roles for HpuA as a meningococcal adhesin and a bacterial factor that inhibits host cell migration.


Copyright Date


Date of Award



Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Molecular Microbiology

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level


Degree Name

Doctor of Philosophy

ANZSRC Type Of Activity code


Victoria University of Wellington Item Type

Awarded Doctoral Thesis



Victoria University of Wellington School

School of Biological Sciences


MacKichan, Joanna; Carter, Philip