Mycobacteria, survival, and universal stress proteins

Universal stress proteins (USPs) have remained an enigma since their first description by Nystrom and Neidhardt in 1992. Despite being upregulated under diverse stresses and found across a range of bacterial species, decades of studies suggested only general and potentially redundant protective functions for USPs. Recent studies have uncovered that USPs are critical regulators of bacterial survival processes in Actinobacteria, most notably in Mycobacterium tuberculosis, one of the most prolific and lethal of human pathogens. This brief review places these recent studies in the context of earlier publications and discusses their importance for future USP research, our understanding of these regulatory proteins, and novel therapeutic options that these proteins present in Mycobacterium tuberculosis, related Actinobacteria, and across diverse bacterial species. Impact Statement Universal stress proteins (USPs) have recently been directly implicated in survival processes in Mycobacteria, related Actinobacteria, and multiple bacterial pathogens. This new understanding identifies these stress-responsive proteins as important targets for mechanistic studies in bacterial survival and promising targets for novel antimicrobial therapeutics.