Why should cell biologists study microbial pathogens?

Welch, Matthew D.

An example of how studying pathogens has advanced our understanding of autophagy mechanisms involves the response to infection by the intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), a common cause of diarrheal illness. S. Typhimurium normally resides within an endosome-like compartment called the Salmonella-containing vacuole (SCV). However, observation of the bacteria that occasionally damage the SCV and escape into the cytosol enabled the discovery of previously unknown mechanisms by which pathogens are targeted to autophagy. These include marking bacteria in the cytosol with ubiquitin (Thurston et al., 2009) and marking those in damaged SCVs with the lectin galectin-8, which recognizes glycans on damaged vacuoles (Thurston et al., 2012) . Both galectin-8 and ubiquitin are then recognized by adapter proteins (including NDP52, p62, and optineurin), which recruit LC3 and initiate autophagosome formation (Thurston et al., 2009 (Thurston et al., , 2012 Zheng et al., 2009; Wild et al., 2011) . In addition to their roles in infection, these same pathways may be involved in targeting damaged organelles in uninfected cells (Huang and Brumell, 2014; Sorbara and Girardin, 2015) and in removing protein aggregates, for example, those associated with neurodegenerative diseases (Rubinsztein et al., 2015) .