Intralysosomal pathogens differentially influence the proteolytic potential of their niche

ABSTRACT: Avoiding lysosomal degradation is vital to the success of intracellular pathogens. The Gram-negative bacterium C. burnetii and protozoan parasites of the Leishmania genus share the unique ability to replicate within a host phagolysosomal compartment, though the exact mechanisms utilised to withstand this hostile environment are not clearly defined. We recently reported that C. burnetii removes the lysosomal protease cathepsin B during infection of mammalian cells. Here, we aimed to determine if this virulence strategy was also employed by the intralysosomal pathogen L. mexicana. The activity of specific cathepsins was analysed, using immunoblotting and protease activity-based probes, and the changes observed during infection with C. burnetii were not observed during L. mexicana infection. Co-infection of THP-1 macrophage like cells with both pathogens resulted in a proteolytic and secretory phenotype consistent with C. burnetii infection, suggesting that C. burnetii-induced remodelling of the lysosome is not influenced by L. mexicana. The host cell proteome and secretome of L. mexicana infected cells was defined using mass spectrometry. This confirmed that, unlike C. burnetii, L. mexicana does not induce increased abundance of lysosomal proteins either intracellularly or in the extracellular milieu. Collectively, this study reveals that although C. burnetii and L. mexicana reside in a phagolysosomal intracellular niche, they employ divergent mechanisms to survive within this hostile compartment.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Lauren Bird  

LAB HEAD: Prof Hayley Newton

PROVIDER: PXD063745 | Pride | 2025-12-22

REPOSITORIES: Pride