Using genomics to improve Bacillus anthracis diagnostics and outbreak investigations

摘要: The bacterium Bacillus anthracis causes the disease anthrax, primarily in herbivores but many mammals are susceptible to disease. Its infective form is as a dormant spore that can lie soil for decades. Thus, its cycle of infection, it spends most time an inactive state and replication-induced DNA-mutations therefore kept at minimum. Partly due these long periods inactivity, all B. isolates found world genetically very similar. This makes strain characterization difficult requires high-resolution technologies. also has similar DNA-content other spp. diagnostic cross-reactions not uncommon. Anthrax incidence steadily declined during last century there still endemic areas. In 2008 2011 Sweden suffered two large costly outbreaks, likely caused by disturbance old anthrax epizootic graves from 1940s 1950s. Several studies emanated outbreaks including how bacteria cows treated with penicillin developed resistance. Next-generation sequencing (NGS) revolutionized way DNA sequenced whole genome (i.e., DNA) now be only few days. this doctoral thesis, NGS genomics were used improve our capability deal outbreaks. Genomic genetic applied identify non-anthrax available closely related anthracis. How well strains could mimic model system spores was evaluated best have since been exercises controls real samples. For comparisons, software created compare content several hundreds bacterial genomes. ensures rapid outbreak pathogen’s genome. silico-compare published PCR-assays determine which assays had highest specificity. workflow molecular diagnostics specific possible. By using outbreak, mechanisms beta-lactam resistance studied chromosomal mutations negative sigma factor cause. genomic divergence gain knowledge strengths limitations epidemiological investigations. In summary, thesis describes different approaches improved methods, explained ambiguous antimicrobial findings enhanced resolution investigation ensure robust handling future outbreaks.