Epidemiology of Paenibacillus larvae, causative agent of American foulbrood

Paenibacillus larvae is the causative agent of American foulbrood (AFB), a damaging disease of honey bees (Apis mellifera) with a global distribution. AFB infects the honey bee larvae through spore-contaminated larval food and once infected the larvae will die within twelve days. AFB infection leads to the eventual death of the honey bee colony. In many countries the best control method is thought to be the destruction of the colony, to destroy the hardy, infectious spores. Therefore infection nearly always leads to the death of the colony. In the UK cases of the disease have decreased in recent years due to statutory control methods, however sporadic outbreaks occur each year. Many advances have been made in our knowledge of the mechanisms of infection by P. larvae in recent years however, a high resolution, standardised method of strain typing is required to track disease spread and understand outbreak sources. This thesis describes the development of the first multilocus sequence typing (MLST) scheme for P. larvae. MLST is the gold standard for pathogenic bacteria typing. It is based on the sequencing of sections of 6-10 housekeeping genes. MLST is standardised, as primer and allele sequences can be made available for other researchers. The new MLST scheme was used to describe previously undetectable patterns of distribution at a global level as well as at a national level. Humans and bees are implicated in the movement of the disease over different spatial scales. Using the MLST scheme a diverse group of isolates were selected for whole genome sequencing. For the first time multiple genomes were compared within and between genotypes. The ability of the MLST scheme to describe relationships amongst sequence types (STs) was tested by comparing phylogenies based on core genes and MLST sequences. I describe the discovery of seven plasmids in four STs previously unknown to harbour plasmids.