Division and cell envelope regulation by Ser/Thr phosphorylation: Mycobacterium shows the way.

Mycobacterium tuberculosis (M. tb) has a complex lifestyle in different environments and involving several developmental stages. The success of M. tb results from its remarkable capacity to survive within the infected host, where it can persist in a non-replicating state for several decades. The survival strategies developed by M. tb are linked to the presence of an unusual cell envelope. However, little is known regarding its capacity to modulate and adapt production of cell wall components in response to environmental conditions or to changes in cell shape and cell division. Signal sensing leading to cellular responses must be tightly regulated to allow survival under variable conditions. Although prokaryotes generally control their signal transduction processes through two-component systems, signalling through Ser/Thr phosphorylation has recently emerged as a critical regulatory mechanism in bacteria. The genome of M. tb possesses a large family of eukaryotic-like Ser/Thr protein kinases (STPKs). The physiological roles of several mycobacterial STPK substrates are connected to cell shape/division and cell envelope biosynthesis. Although these regulatory mechanisms have mostly been studied in Mycobacterium, Ser/Thr phosphorylation appears also to regulate cell division and peptidoglycan synthesis in Corynebacterium and Streptomyces. This review focuses on the proteins which have been identified as STPK substrates and involved in the synthesis of major cell envelope components and cell shape/division in actinomycetes. It is also intended to describe how phosphorylation affects the activity of peptidoglycan biosynthetic enzymes or cell division proteins.