“…4 However, most subsequent studies have focused on these signaling cascades as being indispensable for virulence in a variety of human pathogens. [5][6][7][8][9][10][11][12][13][14][15] The 'genomic age' has revealed a considerable expansion of the eSTK protein family and the presence of their cognate eSTPs in most prokaryotic Phylums, which include important Gram-negative human pathogens such as Pseudomonas aeruginosa, 9,16 and many Gram-positives such as Enterococcus faecalis, 17 Staphylococcus aureus, 12,14,[18][19][20] Mycobacterium tuberculosis, 6,21,22 Streptococcus pneumoniae, 7,23,24 Streptococcus agalactiae 8 and Streptococcus pyogenes. 10,25 This discovery led to the realization that unlike TCS histidine kinases, which almost exclusively target a single response regulator partner, eSTK substrates are instead quite pleiotropic in nature.…”