Cell Biology of Infection

Why Salmonella enterica serovar Typhi infect only humans?

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One central question that we are addressing is about the host mechanisms restricting Salmonella Typhi from infecting non-susceptible hosts.

 

Salmonella Typhi is an exclusive human pathogen and the cause of typhoid fever, a life-threatening systemic disease that affects millions of people and kills more than 200,000 every year. The goal of our research is to gain insights into the molecular and cellular mechanisms of Salmonella Typhi pathogenesis and its human-adaptation. We use an advanced cell biological approach, where imaging and biochemical analyses are integrated by genetic, genomic and proteomic methods. These studies are also intended to address fundamental questions in the cell biology of the host.

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We recently discovered a novel host-defence mechanism that protects against Salmonella Typhi  infections. We showed that Salmonella Typhi clearance ex vivo in macrophages, and in vivo in mice, depends on an intracellular trafficking pathway regulated by the Rab GTPase Rab32 and its guanine nucleotide exchange factor (GEF) BLOC3 (BLOC-3 and Rab32 dependent Anti-Microbial, BRAM pathway). 

 

We are actively studying this pathway and aiming to answer the following questions: 

 

- How is the Rab32-dependent trafficking pathway regulated?

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- Is the Rab32-dependent trafficking pathway active in human macrophages?  If so, how does Salmonella Typhi evade killing and replicate in human macrophages?  

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- What killing molecules does the BRAM pathway deliver to the bacterial containing vacuole?

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- Is it possible to stimulate it and "boost" innate immunity mechanisms?

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