Comparative analysis of macrophage post-translational modifications during intracellular bacterial pathogen infection [article]

Jeffrey R Johnson, Trevor Parry, Teresa Repasy, Kristina M Geiger, Erik Verschueren, Jonathan M Budzik, David Jimenez-Morales, Billy W Newton, Emma Powell, Laurent Coscoy, Daniel A Portnoy, Nevan J Krogan (+1 others)
2020 bioRxiv   pre-print
Macrophages activate robust antimicrobial functions upon engulfing virulent bacteria, yet a wide array of pathogens paradoxically thrive within these innate immune cells. To probe the pathogen-macrophage interface, we used proteomics to comprehensively quantify changes in post-translational modifications (PTMs) of host proteins during infection with three evolutionarily diverse intracellular pathogens: Mycobacterium tuberculosis, Salmonella enterica serovar Typhimurium, and Listeria
more » ... isteria monocytogenes. Comparing global phosphorylation and ubiquitylation patterns identified extensive reprogramming of cellular pathways during infection, with ubiquitylation patterns revealing unique pathogen-specific molecular response signatures undetectable by transcriptional profiling. Differential PTM changes during infection with attenuated M. tuberculosis cells lacking the ESX-1 virulence determinant revealed extensive modification of phagosome dynamics and antiviral type I interferon activation. We found that M. tuberculosis-mediated activation of the antiviral OASL1-IRF7 pathway promotes bacterial replication, uncovering a new mechanism of virus-bacterial synergy. Our data reveals remarkable specificity in innate cellular responses to complex stimuli and provides a resource for deeper understanding of host-pathogen interactions.
doi:10.1101/2020.05.27.116772 fatcat:4sbovyqnxbclpfm22sqxp6tzkm