Dissecting the cyclic di‐guanylate monophosphate signalling network regulating motility in Salmonella enterica serovar Typhimurium

Abstract

Flagella-mediated swimming and swarming motility in Salmonella enterica serovar Typhimurium is intercalated with the cyclic di-guanylate monophosphate (c-di-GMP) signalling network. In this study, we identified the GGDEF domain proteins STM2672, STM4551 and STM1987 as key di-guanylate cyclases involved in regulation of motility in a ΔyhjH phosphodiesterase gene deletion mutant with elevated c-di-GMP levels inhibiting motility. Surprisingly, these di-guanylate cyclases distinctively inhibited motility through the c-di-GMP receptors YcgR and the cellulose synthase BcsA, whereby STM2672 corresponded to YcgR, STM1987 to BcsA and STM4551 to both receptors. Although downregulation of motility is believed to prepare the bacterial cells for surface adhesion and biofilm formation, the major biofilm regulator CsgD of S. sv. Typhimurium was not involved in the regulation of swimming or swarming motility. Together with previously identified c-di-GMP networks regulating flagella-related phenotypes, flagella biosynthesis is a major target of c-di-GMP signalling in S. sv. Typhimurium.

A Diguanylate Cyclase Acts as a Cell Division Inhibitor in a Two-Step Response to Reductive and Envelope Stresses

“…S1 in the supplemental material. Similar data were also recently published independently (17). Of the 18 proteins examined, four were seen to affect motility (see Fig.…”

“…Consistent with the proposal in P. aeruginosa , derepression of YfiN caused by disruption of the inhibitor YfiR enhances biofilm formation by activating cellulose production in E. coli (18, 20). In Salmonella , YfiN was reported to contribute to cellular c-di-GMP levels and inhibit motility through the c-di-GMP receptor YcgR (17). The Yfi system has been suggested to play an important role in the host colonization and persistence of P. aeruginosa , as well as a uropathogenic E. coli strain (16, 19, 20).…”

Bistable Expression of CsgD in Salmonella enterica Serovar Typhimurium Connects Virulence to Persistence

“…YdiV represses expression of yhjH and also negatively regulates motility (53). It is possible that the synthesis of YcgR and YdiV results in localized effects within the cell, but the overall c-di-GMP pool is predominantly influenced by the increased expression of yhjH (46,47). In general, the RNA-seq findings were consistent with the levels of c-di-GMP detected and the predicted phenotypes of planktonic cells and multicellular aggregates.…”

“…Two diguanylate cyclase (DGC) (i.e., c-di-GMP-generating enzymes) genes, STM1987 (45) and adrA (46), were more highly expressed in aggregates at TP2, which correlated with higher levels of c-di-GMP in these cells. yhjH, which encodes a phosphodiesterase (PDE) (i.e., a c-di-GMP-degrading enzyme) with a critical role in controlling motility (46,47), was more highly expressed in planktonic cells, and this correlated with smaller amounts of c-di-GMP. Genes encoding three diguanylate cyclases characterized as having positive effects on invasion (yeaJ) (48), motility (STM2503) (49), or motility and virulence (STM4551) (49) were more highly expressed in planktonic cells at TP2, which correlated with the predicted phenotype of these cells.…”

Alterations of c‐di‐GMP turnover proteins modulate semi‐constitutive rdar biofilm formation in commensal and uropathogenic Escherichia coli

“…C‐di‐GMP inhibits motility by binding to the molecular brake protein YcgR (Boehm et al., ; Paul, Nieto, Carlquist, Blair, & Harshey, ; Ryjenkov, Simm, Römling, & Gomelsky, ) and through production of cellulose (Le Guyon, Simm, Rehn, & Römling, ; Zorraquino et al., )). Motility is promoted by the key PDE YhjH, which effectively removes motility‐dedicated c‐di‐GMP (Le Guyon et al., ; Pesavento et al., ; Simm et al., ) and consequently the motility/sessility switch is observed upon deletion of YhjH (Simm et al., ) or, more pronounced, upon overexpression of DGCs and PDEs (Simm et al., ). Although csgD represses swimming motility in E. coli K‐12 (Dudin et al., ; Ogasawara, Yamamoto, & Ishihama, ), a correlation between csgD expression and motility was not observed.…”