Heterogeneity; Legionella; Phagocyte; Infection; Trafficking; Proteome; Vacuole; Virulence; Metabolism; Membrane
Personnic Nicolas, Striednig Bianca, Hilbi Hubert (2018), Single Cell Analysis of Legionella and Legionella-Infected Acanthamoeba by Agarose Embedment
, Humana Press, Totowa, NJ.
Striednig Bianca, Personnic Nicolas, Hilbi Hubert (2017), Legionella quorum sensing and its role in pathogen-host interactions., in Current opinion in microbiology
, 41, 29-35.
Steiner Bernhard, Welin Amanda, Personnic Nicolas, Freyre Christophe, Klemm Robin W, Hilbi Hubert, Swart Anna Leoni, Weber Stephen, Kaech Andres, Ziegler Urs (2017), ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila., in EMBO reports
, 18(10), 1817-1836.
Personnic Nicolas, Bärlocher Kevin, Finsel Ivo, Hilbi Hubert (2016), Subversion of Retrograde Trafficking by Translocated Pathogen Effectors., in Trends in microbiology
, 24(6), 450-62.
BuckleyCatherine M, HeathVictoria L, GuehoAurelie, BosmaniCristina, KnoblochPaulina, SikakanaPhumzile, PersonnicNicolas, DoveStephen K, MichellRobert H, MeierRoger, HilbiHubert, SoldatiThierry, InsallRobert H, KingJason, PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection, in PLOS Pathogens
An emerging concept holds that genetically identical bacteria show surprisingly high levels of variation in phenotypic traits. Phenotypic noise and stochastic cellular processes are sources of heterogeneity. Furthermore, phenotypic variations also reflect bacterial responses to distinct environments. Recent studies revealed that host tissue micro-environments and the milieu of single host cells trigger phenotypic variation of intracellular bacterial pathogens. However, the molecular bases underlying phenotypic variability are largely unknown.Legionella pneumophila is the causative agent of a severe pneumonia termed “Legionnaires’ disease”. The bacteria replicate within free-living amoebae and lung alveolar macrophages in a distinct membrane-bound compartment, the “Legionella-containing vacuole” (LCV). Formation of this replicative niche involves the bacterial Icm/Dot type IV secretion system (T4SS) and approximately 300 different secreted “effector” proteins. LCVs avoid the fusion with bactericidal lysosomes, but communicate with the endosomal, secretory and retrograde vesicle trafficking pathways, and eventually fuse with the endoplasmic reticulum (ER). One may suggest that LCVs subversion of host cell membrane trafficking is required to support bacterial growth by providing required membranes, nutrients and host cell factors.L. pneumophila employs a biphasic life style to switch between intracellular replication and transmission to new hosts. In vitro, exponentially growing bacteria repress transmissive traits and induce these features upon entering the stationary phase. The transition is reversible and triggered by nutrient limitation and/or the bacterial density. Recent preliminary experiments using a fluorescent reporter revealed the emergence of heterogeneous subpopulations of L. pneumophila in infected phagocytes.In this application, I propose to characterize in detail the phenotypic heterogeneity of intracellular L. pneumophila in Dictyostelium discoideum amoebae and mammalian macrophages. To this end, heterogeneity in the growth rate, metabolism, virulence and motility of the bacteria will be assessed at a single cell level in dependence of the bacterial and host cell genotype and in response to the small bacterial signaling molecule LAI-1, nutrients and antibiotics.