Quorum sensing governs a transmissive Legionella subpopulation at the pathogen vacuole periphery

다국어 초록 (Multilingual Abstract)

The Gram‐negative bacterium Legionella pneumophila is the causative agent of Legionnaires' disease and replicates in amoebae and macrophages within a distinct compartment, the Legionella‐containing vacuole (LCV). The facultative intracellular pathogen switches between a replicative, non‐virulent and a non‐replicating, virulent/transmissive phase. Here, we show on a single‐cell level that at late stages of infection, individual motile (PflaA‐GFP‐positive) and virulent (PralF‐ and PsidC‐GFP‐positive) L. pneumophila emerge in the cluster of non‐growing bacteria within an LCV. Comparative proteomics of PflaA‐GFP‐positive and PflaA‐GFP‐negative L. pneumophila subpopulations reveals distinct proteomes with flagellar proteins or cell division proteins being preferentially produced by the former or the latter, respectively. Toward the end of an infection cycle (˜ 48 h), the PflaA‐GFP‐positive L. pneumophila subpopulation emerges at the cluster periphery, predominantly escapes the LCV, and spreads from the bursting host cell. These processes are mediated by the Legionella quorum sensing (Lqs) system. Thus, quorum sensing regulates the emergence of a subpopulation of transmissive L. pneumophila at the LCV periphery, and phenotypic heterogeneity underlies the intravacuolar bi‐phasic life cycle of L. pneumophila.










Legionella forms a distinct vacuole in phagocytes, wherein the pathogen adopts a bi‐phasic life cycle and phenotypic heterogeneity. Quorum sensing elicits a transmissive subpopulation at the vacuole periphery, which spearheads compartment exit and host cell lysis.

Legionella pneumophila switches between a replicative and a virulent/transmissive phase in its unique intracellular vacuole.
The intravacuolar bi‐phasic life cycle displays phenotypic heterogeneity.
Quorum sensing elicits a transmissive subpopulation at the vacuole periphery, promoting compartment exit and cell lysis.

Legionella forms a distinct vacuole in phagocytes, wherein the pathogen adopts a bi‐phasic life cycle and phenotypic heterogeneity. Quorum sensing elicits a transmissive subpopulation at the vacuole periphery, which spearheads compartment exit and host cell lysis.