(A) The heatmaps shows loci whose disruption changed susceptibility to all three β-lactams tested (See Materials and Methods). Hierarchical clustering was used to order both genes and drugs [84]. Table S2 lists the genes with annotations. (B) Both transposon insertions that disrupt genes that encode flagella components as well as insertions that indirectly reduce flagella synthesis by activating the Rcs system are beneficial. The core components of the Rcs system are RcsC, a hybrid sensor kinase, RcsD, a histidine phosphotransferase, and RcsB, a DNA-binding response regulator [89]. Other components are RcsF, a lipoprotein that activates RcsC [90], [91], and RcsA, a transcription factor that forms a heterodimer with RcsB [92]. Together, RcsA and RcsB repress transcription of flhDC, the master regulator of flagella synthesis [51]. RcsA is a target of the Lon protease [93], and insertions in lon, which stabilize RcsA, are beneficial. RcsC and RcsD both transfer phosphate to as well as remove phosphate from RcsB, resulting in higher activation of the Rcs system in rcsC or rcsD mutants than in wildtype [90], [94]. Insertions in mdoG and mdoH, which encode proteins that synthesize osmoregulated periplasmic glucans (OPGs), reduce motility by activating the Rcs system [25]. The beneficial effects of mdoG, modH, and rcsC disruptions are not limited to β-lactams (Figure 7).