Legionella; Bet-hedging; Eco-pathology; Vacuole; Heterogeneity; Community; Subpopulation; Amoeba; Proteome; Quorum-sensing; ncRNA; Virulence; Persister; Metabolism
Knobloch Paulina, Koliwer‐Brandl Hendrik, Arnold Fabian M., Hanna Nabil, Gonda Imre, Adenau Sophia, Personnic Nicolas, Barisch Caroline, Seeger Markus A., Soldati Thierry, Hilbi Hubert (2020), Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes, in Cellular Microbiology
Personnic Nicolas, Striednig Bianca, Lezan Emmanuelle, Manske Christian, Welin Amanda, Schmidt Alexander, Hilbi Hubert (2019), Quorum sensing modulates the formation of virulent Legionella persisters within infected cells, in Nature Communications
, 10(1), 5216-5216.
Buckley Catherine M., Heath Victoria L., Guého Aurélie, Bosmani Cristina, Knobloch Paulina, Sikakana Phumzile, Personnic Nicolas, Dove Stephen K., Michell Robert H., Meier Roger, Hilbi Hubert, Soldati Thierry, Insall Robert H., King Jason S. (2019), PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection, in PLOS Pathogens
, 15(2), e1007551-e1007551.
Personnic Nicolas, Striednig Bianca, Hilbi Hubert (2019), LegionellaMethods and Protocols
, Springer New York, New York, NY.
Clonal bacterial populations show remarkable cell-to-cell variations in the expression of phenotypic traits, a phenomenon termed phenotypic heterogeneity. Legionella pneumophila is a facultative intracellular, Gram-negative bacterial pathogen ubiquitously found in nature. It is the responsible agent for the potentially life-threatening pneumonia called Legionnaires’ disease. L. pneumophila resides in multi-species biofilms hosting protozoan predators, survives its ingestion by the free living amoeba Acanthamoeba castellanii, and replicates in a customized intracellular compartment, the Legionella containing vacuole (LCV). The Legionella Quorum Sensing (LQS) is key to colonize those different niches.Using adequate fluorescent reporters and single cell techniques, we investigated for the first time the single cell behavior of L. pneumophila. We discovered that heterogeneous expression of the LQS signal organizes non-growing, yet virulent, bacteria in functionally distinct subpopulations. This alternative “priming” leads to a marked growth rate heterogeneity in infected amoeba and promotes persister formation. Interestingly, those persisters reside in distinct ad hoc LCV, remains virulent, yet non-replicative, and show specific proteomic signatures.At the later stage of infection, A. castellanii amoebae host a large number of clustered bacteria originating from the pool of replicating bacteria. Strikingly, the bacterial population shows phenotypically distinct individual bacteria that are spatially organized. The observed phenotypic heterogeneity is, at least partially, dependent on environmental cues. At the end of the infection cycle, the host cell undergoes explosive lysis and releases its contents into the environment. This spectacular finale raises the question of the functional consequences of distinct intracellular bacterial subpopulations.In this follow-up proposal, I propose to decipher molecular basis and the functional consequences of the observed L. pneumophila intra-cellular community behavior. The specific aims of this proposal are:2) To study L. pneumophila community traits and subpopulation spatial organization in infected amoeba.3) To characterize the temperature-dependent bistable expression of L. pneumophila non-coding RNA