Spatiotemporal proteomics uncovers cathepsin-dependent macrophage cell death during Salmonella infection.

ABSTRACT: The interplay between host and pathogen relies heavily on rapid protein synthesis and accurate protein targeting to ensure pathogen destruction. To gain insight into this dynamic interface, we combined Click chemistry with pulsed stable isotope labelling of amino acids in cell culture to quantify the host proteome response during macrophage infection with the intracellular bacterial pathogen Salmonella enterica Typhimurium. We monitored newly synthesized proteins across different host cell compartments and infection stages. Within this rich resource, we detected aberrant trafficking of lysosomal proteases to the extracellular space and the nucleus. We verified that active cathepsins re-traffic to the nucleus and that these are linked to cell death. Pharmacological cathepsin inhibition and

SUBMITTER: Selkrig J 

PROVIDER: S-EPMC7610801 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature