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Bacterial pathogens

Our work on bacterial pathogens focuses mainly on Neisseria meningitidis which is a frequent commensal of the human nasopharynx but occasionally gives rise to meningitis and septicaemia. In industrialised countries, carriage rates are approximately 10% for the population as a whole, with the highest rates in young adults, approaching 35%. N. meningitidis may be stratified into serogroups on the basis of their polysaccharide capsule, which surrounds the outer membrane and acts as a target for mucosal and humoral immunity. 

Vaccines have been developed against serogroups A and C, but there is no effective vaccine against serogroup B which causes approximately 50% of meningococcal disease cases worldwide. There are vaccine candidates among the outer membrane proteins (OMPs), such as the porins, FetA and opa proteins, but these typically exhibit high variability.

We have a long-term collaboration with Prof. Martin Maiden's group in this area, and we have together demonstrated that many of the variable regions of these OMPs are organised into non-overlapping combinations (or discrete antigenic types) as predicted by the multi-locus models of immune selection.

We have also shown that genes performing metabolic functions may also exhibit long-term linkage disequilibrium as a consequence of immune selection acting on shared antigenic determinants. We are currently extending this work on the interactive evolution of loci that are not under direct immune selection (e.g. housekeeping genes) with those diverse epitopes that are under strong immune selection to explore the evolution of virulence in this system and assess the impact of vaccination on population structure.

References

  1. Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM & Anderson RM (1996) The maintenance of strain structure in populations of recombining infectious agents. Nature Medicine 2(4): 437 442. PDF
  2. Buckee CO, Jolley KA, Recker M, Penman B, Kriz P, Gupta S & Maiden M. (2008) Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis. Proc Natl Acad Sci U S A 105:15082-7. PDF
  3. Buckee CO, Gupta S, Kriz P, Maiden MC & Jolley KA (2010) Long-term evolution of antigen repertoires among carried meningococci.  Proc Biol Sci 277:1635-41. PDF
  4. Buckee CO, Recker M, Watkins ER, Gupta S (2011) Role of stochastic processes in maintaining discrete strain structure in antigenically diverse pathogen populations. Proc Natl Acad Sci U S A108(37):15504-15509. PDF