Project Details
Projekt
Regulation of phenotypic switching and heterogeneity in Photorhabdus luminescens cell populations
Applicant
Professor Dr. Ralf Heermann
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
from 2012 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 217713783
Photorhabdus luminescens is an insect pathogenic bacterium that lives in close symbiosis with specific soil nematodes. The bacteria have a complex life cycle consisting of a symbiotic stage colonizing the intestinal tract of the nematodes, and a pathogenic stage outside of the nematodes within insect larvae. P. luminescens exist in two phenotypically different forms, designated as primary and secondary variants that are genetically homogeneous but differ in various morphological and physiological traits. During prolonged growth, secondary cells arise spontaneously with the result that 20-50% of the cells have undergone the transition after 28 days. This correlates with the time point when nematodes and bacteria have been re-associated and emerge from the insect cadaver. The cells that have undergone phenotypic switching are disabled in re-association and symbiosis with the nematodes. The reason for phenotypic heterogeneity of P. luminescens cell populations is rarely understood. It is assumed that secondary cells are better adapted for a life in the soil, so that splitting of the population is assumed to be a bet-hedging strategy that ensures survival of the population under any condition. However, P. luminescens cells have never been isolated from the soil, probably because they exist as metabolically inactive persister cells. The signals that induce reverse switching from the secondary to the primary variant or that can awake persister cells are unknown so far. It emerged from the previous funding period that secondary cells secrete a signal that induces the switching process in primary cells. Furthermore, primary cells emerged to inhibit growth of secondary cells revealing a simple sociobiological relation between both phenotypic variants. Identification of the chemical nature of these signals as well as the fate of the secondary cells are central questions that will be addressed in the current funding period. Furthermore, the molecular mechanism of phenotypic switching regulation will be investigated. The LysR-type regulator HexA has been identified as global regulator of the switching process. It emerged from the previous funding period that HexA is a versatile regulator that can directly or indirectly influence phenotypic heterogeneity at the transcriptional as well as the post-transcriptional level, probably via small regulatory RNAs. Identification of these small RNAs as well as the signal that is sensed by HexA to activate the switching process in single cells are further central questions that will be addressed in the current funding period. Mathematical modeling of phenotypic switching of P. luminescens will be used to contribute to the understanding of general regulation mechanisms of phenotypic heterogeneity in bacteria.
DFG Programme
Priority Programmes
