regulation of exit; lysis; predatory bacterium; Bdellovibrio bacteriovorus
Harding Christopher J., Huwiler Simona G., Somers Hannah, Lambert Carey, Ray Luke J., Till Rob, Taylor Georgina, Moynihan Patrick J., Sockett R. Elizabeth, Lovering Andrew L. (2020), A lysozyme with altered substrate specificity facilitates prey cell exit by the periplasmic predator Bdellovibrio bacteriovorus, in Nature Communications
, 11(1), 4817.
Background: Gram-negative predatory bacterium Bdellovibrio bacteriovorus is prevalent in the environment and might turn out to be very useful as a ‘living antibiotic’. It invades other Gram-negative prey bacteria and replicates in their periplasm. Once resources run out, predator progeny escape the surrounding exhausted prey cell remnants. Objectives: This release process is multifactorial but barely understood from a molecular mechanistic point of view including molecular identity of the signal triggering the exit process and the underlying regulatory network. These aspects were investigated in this research project. Methods and Results: Our newly generated transcriptional data of this exit phase revealed three upregulated genes potentially involved in signalling and four upregulated genes of high interest encoding secreted hypothetical proteins attributed to a periplasmatic predatory lifestyle. All these genes were deleted in this Postdoc.Mobility Fellowship. Research with regards to signalling at the end of the predatory life cycle was stalled, due to a lack of obvious phenotype of three gene-deletion mutants of the predator. In contrast, investigation on four other predatory genes likely involved in the prey exit process is ongoing in the Postdoc.Mobility Return Fellowship. Further, the findings on exit-specific lysozyme DslA of the Early Postdoc.Mobility Fellowship were consolidated by additional controls, affirming a role of DslA in the prey exit process in contrast to other predatory lysozyme homologues.Expected value of the proposed project: This project characterized an exit-specific lysozyme DslA in more detail (collaboration with Prof. R. E. Sockett and Dr. A. L. Lovering), while starting to investigate four additional genes likely involved in the prey escape process. DslA could be a useful tool to investigate and potentially damage Gram-positive pathogens that deacetylate their cell wall to escape conventional lysozyme activity. Novel modes of action, especially in context of bacterial cell envelope damaging activity, are of potential interest for new drugs acting against bacteria. To make use of this predator or parts of it, it is crucial to understand the molecular mechanisms underlying Gram-negative prey manipulation by the predator.