SuhB Regulates the Motile-Sessile Switch in Pseudomonas aeruginosa through the Gac/Rsm Pathway and c-di-GMP Signaling

Abstract

Many Pseudomonas aeruginosa virulence traits that contribute to human infections are accepted as being associated with its environmental lifestyle. Therefore, identifying the molecular mechanisms that govern the lifestyle choice is of high significance. We previously reported that a mutation in suhB results in a decrease in swimming motility and increased biofilm formation compared to the wild-type strain. Yet, little is known about how this occurs. In this study, we demonstrated that SuhB inversely regulates motility and biofilm formation through the GacA-RsmY/Z-RsmA cascade. Mutations in gacA or the two small RNAs rsmY/rsmZ, or overproduction of the RsmA protein essentially rescued the motility defect of the suhB mutant. Additionally, we identified a c-di-GMP mediated mechanism for SuhB regulation of motility and biofilm formation. We showed that the ΔsuhB mutant displayed elevated levels of c-di-GMP, and the ΔsuhB motility and biofilm phenotypes could be switched by artificially decreasing c-di-GMP levels. Further experiments led to the identification of the diguanylate cyclase GcbA responsible for regulating the c-di-GMP concentration in ΔsuhB and hence the switch between planktonic and surface-associated growth. Together, our results demonstrate a novel mechanism for SuhB regulation of the lifestyle transition via the Gac/Rsm and c-di-GMP signaling networks in P. aeruginosa.

Fitting Pieces into the Puzzle of Pseudomonas aeruginosa Type III Secretion System Gene Expression

“…SuhB inhibits the DGC GcbA, resulting in decreased c-di-GMP levels (Fig. 3) (146). SuhB also inhibits the expression of GacA (113).…”

“…Overexpression of some DGCs inhibits cAMP-Vfr-dependent reporter activity, and overexpression of some PDEs stimulates reporter activity. DGCs with potential relevance to T3SS gene control include WspR, SiaD, SadC, MucR, and GcbA, and implicated PDEs include PvrR, RocR, FcsR, PA2200, PA3825, NbdA, BifA, DipA, and RbdA (96,113,126,(141)(142)(143)(145)(146)(147)(148)(149)(150)(151)(152) (Fig. 3).…”

Complex Signaling Networks Controlling Dynamic Molecular Changes in Pseudomonas aeruginosa Biofilm

“…Another newly discovered DGC/TCS co-operation module regards to GcbA as the main element of SuhB regulon. The GcbA inhibits fliC expression and activates the TCS Gac/Rsm system [98] causing T6SS production and biofilm formation. Moreover, the SuhB-dependent signal pathway results in an increased tolerance to aminoglycosides conditioned by ribosome modification [99].…”

An Osmoregulatory Mechanism Operating through OmpR and LrhA Controls the Motile-Sessile Switch in the Plant Growth-Promoting Bacterium Pantoea alhagi

“…KEYWORDS LrhA, OPGs, OmpR, Rcs phosphorelay, biofilm, exopolysaccharides, motility, osmosensing I n nature, bacteria employ various adaptive strategies to cope with changing environments (1)(2)(3). Notably, many bacteria are able to develop two different lifestyles, the planktonic mode (characterized by single motile cells) and the biofilm mode (characterized by sessile multicellular communities that are attached to each other and a surface) (4,5). While the transition between motile and sessile lifestyles of bacteria is crucial for their ecological success, complex regulatory networks are integrated to achieve the control of the motile-sessile switch in response to a variety of environmental signals, including nutrient availability, oxygen, temperature, salinity, metal ions, calcium, and phosphate (6)(7)(8)(9)(10).…”

“…In general, flagellum formation is turned off and EPS production is turned on during the switch from planktonic to biofilm growth, whereas biofilm dispersal is preceded by decreased EPS production and increased flagellar motility (23,25,26). Accordingly, the bacterial second messenger cyclic dimeric GMP (c-di-GMP) has been widely demonstrated to be involved in the regulation of EPS biosynthesis, flagellar motility, and the transition from the motile to the sessile/biofilm state (4,5,23). In addition, a wide array of regulatory factors such as BolA (26), CsgD (27), and CsrA (28) in Escherichia coli and quorum-sensing systems in Paraburkholderia phytofirmans PsJN (22) have been shown to control the transition between planktonic and biofilm lifestyles through playing a dual role in the control of biofilm EPS production and flagellar activity.…”