Agents of change – concepts in M ycobacterium tuberculosis Ser / Thr / Tyr phosphosignalling

Summary The flow of information from the outside to the inside of bacterial cells is largely directed by protein kinases. In addition to histidine/aspartate phosphorelays of two‐component response regulators, recent work in M ycobacterium tuberculosis ( M tb ) reinforces the idea that phosphorylation on serine ( S er), threonine ( T hr) and tyrosine ( T yr) is central to bacterial physiology and pathogenesis, and that the corresponding phosphosystems are highly similar to those in eukaryotes. In this way, eukaryotes are a useful guide to understanding S er/ T hr/ T yr phosphorylation ( O ‐phosphorylation) in prokaryotes such as M tb . However, as novel functions and components of bacterial O ‐phosphorylation are identified, distinct differences between pro‐ and eukaryotic phosphosignalling systems become apparent. The emerging picture of O ‐phosphorylation in M tb is complicated, goes beyond the eukaryotic paradigms, and shows the limitations of viewing bacterial phosphosignalling within the confines of the ‘eukaryotic‐like’ model. Here, we summarize recent findings about S er/ T hr and the recently discovered T yr phosphorylation pathways in M tb , highlight the similarities and differences between eukaryotic and prokaryotic O ‐phosphorylation, and pose additional questions about signalling components, pathway organization, and ultimately, the cellular roles of O ‐phosphorylation in M tb physiology and pathogenesis.