The enterococcal PASTA kinase: A sentinel for cell envelope stress

Enterococci are Gram‐positive, opportunistic pathogens that reside throughout the gastrointestinal tracts of most terrestrial organisms. Enterococci are resistant to many antibiotics, which makes enterococcal infections difficult to treat. Enterococci are also particularly hardy bacteria that can tolerate a variety of environmental stressors. Understanding how enterococci sense and respond to the extracellular environment to enact adaptive biological responses may identify new targets that can be exploited for development of treatments for enterococcal infections. Bacterial eukaryotic‐like serine/threonine kinases (eSTKs) and cognate phosphatases (STPs) are important signaling systems that mediate biological responses to extracellular stimuli. Some bacterial eSTKs are transmembrane proteins that contain a series of extracellular repeats of the penicillin‐binding and Ser/Thr kinase‐associated (PASTA) domain, leading to their designation as “PASTA kinases.” Enterococcal genomes encode a single PASTA kinase and its cognate phosphatase. Investigations of the enterococcal PASTA kinase revealed its importance in resistance to antibiotics and other cell wall stresses, in enterococcal colonization of the mammalian gut, clues about its mechanism of signal transduction, and its integration with other enterococcal signal transduction systems. In this review, we describe the current state of knowledge of PASTA kinase signaling in enterococci and describe important gaps that still need to be addressed to provide a better understanding of this important signaling system.