Intrinsic Disorder as a New Frontier in Antimicrobial Resistance and Bacterial Fitness

Intrinsically disordered proteins (IDPs) are biological macromolecules lacking a well-defined structure under normal physiological conditions. These proteins can be essential for both eukaryotic and prokaryotic cells, yet bacterial IDPs are significantly understudied. In this review, we highlight the functional importance of intrinsic disorder across a range of microbial phenomena, including effector secretion, desiccation tolerance, and the bacterial stress response. Given the emergence of structural disorder in key mechanisms of bacterial fitness, we propose bacterial intrinsic disorder as a novel linkage to antimicrobial resistance (AMR). We highlight areas of research where further study of bacterial IDPs could provide new insights into microbial evolution. Functional disorder introduces a new paradigm to the challenge of AMR, identifying novel targets for antimicrobial therapy.