Unstructured but dangerous—the emerging roles of intrinsically disordered protein regions in bacterial pathogenesis

Intrinsically disordered regions (IDRs) constitute a substantial portion of eukaryotic proteomes but are less prevalent in prokaryotes. Nevertheless, accumulating evidence reveals that IDRs play crucial roles in bacterial virulence, niche adaptation, and host interactions. In this review, we focus on human bacterial pathogens and discuss recent advances in understanding the distribution, evolution, and functional characterization of IDRs. We begin by briefly summarizing their biological properties, conformational ensembles, and representation within bacterial proteomes. We then highlight the diverse mechanisms through which bacterial IDRs interact with and manipulate host cell machineries. These include hijacking host pathways, mediating protein-protein interactions, sensing nutrients and environmental cues, accommodating short linear motifs that mimic eukaryotic signaling elements, and sequestering antimicrobial peptides. Finally, we examine current knowledge and outstanding questions concerning the evolution and antigenicity of bacterial IDRs. Drawing on recent research advances, we provide a focused and accessible overview on how IDRs contribute to the shaping of host-bacteria interactions.