Project Details
Projekt
Evolution of virulence in Paenibacillus larvae, a honey bee pathogenic bacterium
Applicant
Professorin Dr. Elke Genersch
Subject Area
Evolution, Anthropology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 425876005
The virulence of a bacterial pathogen always evolves in a specific host context and is determined by the tripartite interactions between the pathogen, the host and the resident microbiota. At the molecular level, the evolution of bacterial virulence depends on genetic modification of bacterial genomes, followed by selection of beneficial variants. Understanding the drivers and mechanisms of bacterial virulence evolution is critical to understanding host-pathogen systems. Similarly, understanding a particular host-pathogen system is a perfect prerequisite for an informed study of the drivers and mechanisms of virulence evolution of the pathogen of interest. We here propose to study within-host virulence evolution by further exploiting the natural co-evolved host-pathogen system of honey bee larvae and Paenibacillus larvae, a spore-forming, obligate-killing, necrotrophic bacterial entomopathogen that is specialized on a single host (honey bee) and host life stage (larvae). We will study P. larvae virulence evolution from the perspective of molecular infection biology and with emphasis on the basic mechanisms of host-pathogen interaction. To this end, we will leverage our molecular understanding of P. larvae pathomechanisms, which we have gained in the recent past through the identification and characterization of several key virulence factors and secondary metabolites of P. larvae. Despite this wealth of information on P. larvae virulence factors, the evolution of P. larvae virulence is not well understood. In particular, little is known about the selective pressures that both the cadaver microbiota and the presence of additional pathogens exert on P. larvae virulence evolution. We will close this gap in knowledge by (a) assessing the relevance of eliminating competing saprophytes in the necrotrophic phase of the life cycle of P. larvae for its virulence (evolution) and (b) characterizing how the genetic determinants of virulence of P. larvae evolve under the influence of a competing second bacterial pathogen. To achieve these goals, we will use a combination of (i) the newly established protocol for serial passage exposure bioassays, (ii) in vivo and in vitro assays for bacterial multicellular behavior, bacterial growth (inhibition) and secondary metabolite activity, (iii) secondary metabolite purification and characterization, (iv) bacterial gene inactivation mutants, (v) bacterial genome re-sequencing, (vi) amplicon sequencing, and (vii) mathematical / statistical models. The results will add to the growing body of knowledge on P. larvae virulence mechanisms and evolution. Furthermore, understanding the within-host evolutionary players and dynamics of our host-pathogen system will also have general implications for understanding, epidemiology and virulence management strategies for spore-forming, obligate-killing pathogens, in particular those with a necrotrophic life style.
DFG Programme
Research Units
