#FEMSmicroBlog: Intracellular contact sites between pathogen and host


Once inside a host cell, many bacterial pathogens create distinct membrane-bound compartments. Within these ‘pathogen vacuoles’ the bacteria can acquire nutrients and grow to high numbers. The short review “Pathogen vacuole membrane contact sites – close encounters of the fifth kind” in microLife explains why these vacuoles are always in close contact with different host cell membranes. In this #FEMSmicroBlog, Hubert Hilbi outlines how bacterial pathogens exploit contact sites between membranes to promote their own survival. #FascinatingMicrobes 

Upon infection of a host cell, many bacterial pathogens form membrane-bound compartments called ‘pathogen vacuoles’. These protect bacteria from degradation by the host and allow them to survive and grow within the host cell. 

The composition and features of pathogen vacuoles are specific to each bacterium and not always fully characterised. Yet, something is clear: pathogen vacuoles interact with host cell membranes through stable contact sites which the bacterial pathogens hijack to transport molecules.  


Bacterial pathogens hijack intracellular transport

Eukaryotic cells coordinate the intracellular transport of proteins and lipids over long and short distances.  

Transport over long distances is approximately between 1 and 10 µm and occurs by means of vesicles; transport over short distances is up to 30 nm and usually takes place at contact sites between two membranes. This short-range transport involves two different organelles, one of which is usually the endoplasmic reticulum.  

The short reviewPathogen vacuole membrane contact sites – close encounters of the fifth kind” in microLife presents how pathogens hijack long and short-distance transport of proteins and lipids to create their vacuoles. Additionally, they compromise and exploit not only host cell vesicle trafficking pathways but also contact sites with the host cell membrane.  

Intracellular transport in eukaryotic cells: Vesicle transport (A) and membrane contact sites (B). From Vormittag et al. (2023).


Bacterial pathogens secrete effector proteins to establish their vacuoles

The short review focuses on the vacuole-forming abilities of two bacterial pathogens:  Legionella pneumophila, causing Legionnaires’ pneumonia, and Chlamydia trachomatis, causing urogenital tract infections. Within host cells, L. pneumophila and C. trachomatis form the ‘Legionella-containing vacuoles’ and ’Chlamydia inclusions’, respectively. 

These two intracellular pathogens employ type IV or type III secretion systems to deliver dozens if not hundreds of different effector proteins into host cells. The effector proteins subvert crucial cellular processes, including signal transduction, vesicle trafficking and cytoskeletal dynamics.  

Once formed, pathogen vacuoles interfere with components of several vesicle trafficking pathways. The vacuoles can avoid the bactericidal endosomal pathway, circumventing degradation and ensuring the pathogen’s survival. At the same time, pathogen vacuoles subvert the host cell’s secretory pathway, which helps the pathogen replicate. 

Intracellular growth of Legionella pneumophila and formation of membrane contact sites between ‘Legionella-containing vacuoles’ (LCV) and host cell’s endoplasmic reticulum (ER). From Vormittag et al. (2023).


Additionally, the Legionella-containing vacuole and the Chlamydia inclusion establish stable contact sites with the host cell’s endoplasmic reticulum. These membrane contact sites contain transporters to exchange lipids between the two compartments.  

In this way, the intracellular pathogen employs lipid transport over short distances to remodel the membrane of its vacuole and adopt specific functions. For example, by incorporating more sterols in the vacuole membrane, its thickness increases while the permeability of solutes decreases. 

Microbiologists are still unravelling the exact composition of vacuole membranes of infected and non-infected cells. Knowledge of their architecture will then help better understand the sophisticated strategies of bacterial pathogens during the infection process. 


About the author of this blog

Hubert Hilbi is a professor and research group leader at the University of Zürich, Institute of Medical Microbiology, since 2015. He earned a PhD in Microbiology from the ETH Zürich in 1994 and did postdoctoral studies at the New York University Medical Center and the Columbia University in New York, followed by appointments as an assistant and associate professor at the ETH Zürich and the Ludwig Maximilian University in Munich. His research interests are virulence, communication, and persistence of Legionella spp., i.e., the molecular and cellular analysis of secreted bacterial effector proteins and their host cell targets, cell-cell-signalling by low molecular weight compounds, and intracellular metabolism. 

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The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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