Virulence Factors and Motility Mechanisms of Pathogenic Neisseria
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Neisseria gonorrhoeae and Neisseria meningitidis are two closely related human specific pathogens. Neisseria gonorrhoeae is the causative agent for the sexually transmitted disease gonorrhea and often causes asymptomatic infections in women which is a cause of infertility. Neisseria meningitidis is a major cause of mortality world-wide through bacterial meningitis and septicemia. The severity of meningococcal disease, especially in sub-Saharan Africa warrants development of effective vaccines against serogroups that currently lack them. Here, Neisseria host-pathogen interactions and common virulence factors that may prove useful in vaccine development and in understanding disease caused by pathogenic Neisseria are reviewed and investigated. The aim of this thesis is to investigate the virulence-associated properties of the universally expressed N. meningitidis proteins NhhA, NafA, PilU and PilT, as well as to characterize the twitching motility of the pathogenic Neisseria. The conserved autotransporter adhesin NhhA has in Paper I of this thesis been investigated in a murine model of meningococcemia and found to be important for intranasal colonization and disease outcome of N. meningitidis in CD46 transgenic mice. NafA has in Paper II of this thesis been named and identified as a novel anti-aggregation factor that impacts both pilus bundling and the virulence potential of N. meningitidis. The ATPases, PilU and PilT, which are involved in the functionality of pili were studied in Paper III of this thesis. PilU and PilT were found to modulate Neisseria microcolony formation, host cell adhesion, pilus retraction, serum resistance, as well as mortality in a mouse model of meningococcal disease. Finally, Paper IV of this thesis also provides novel insights into the nature of twitching motility in pathogenic Neisseria. By live-cell microscopy and automated particle tracking coupled with visualization of pili in motile bacteria we found that N. meningitidis strains, on average, move faster and utilizes more pili then N. gonorrhoeae. In summary, this thesis investigates Neisseria virulence factors in general, type IV pili in particular and characterizes the roles of several virulence-associated proteins and twitching motility in the pathogenic Neisseria.
Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University , 2012. , 61 p.
Neisseria, Virulence factors, Type IV pili, PilT, PilU, NafA, NhhA, Twitching motility
Research subject Molecular Genetics
IdentifiersURN: urn:nbn:se:su:diva-65812ISBN: 978-91-7447-423-7OAI: oai:DiVA.org:su-65812DiVA: diva2:464886
2012-01-27, sal G, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C, Stockholm, 13:00 (English)
Tønjum, Tone, Professor
Jonsson, Ann-Beth, ProfessorAro, Helena, Forskningsassistent
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.2012-01-042011-12-142014-10-31Bibliographically approved
List of papers