Self-produced exopolysaccharide is a signal that stimulates biofilm formation in<i>Pseudomonas aeruginosa</i>

Irie, Yasuhiko; Borlee, Bradley R.; O'Connor, Jennifer Ruth; Hill, Preston J.; Harwood, Caroline S.; Wozniak, Daniel J.; Parsek, Matthew R.

doi:10.1073/pnas.1217993109

Cited by 260 publications

(261 citation statements)

References 32 publications

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“…Interestingly, self-induced stimulation of exopolysaccharide production has previously been described for Psl, the polysaccharide component of the extracellular matrix of Pseudomonas aeruginosa biofilms (Irie et al 2012). Importantly, Parsek and coworkers (Irie et al 2012) have shown that purified Psl can stimulate its own production.…”

Section: Discussionmentioning

confidence: 96%

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

2014

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We report that the Bacillus subtilis exopolysaccharide (EPS) is a signaling molecule that controls its own production. EPS synthesis depends on a tyrosine kinase that consists of a membrane component (EpsA) and a kinase component (EpsB). EPS interacts with the extracellular domain of EpsA, which is a receptor, to control kinase activity. In the absence of EPS, the kinase is inactivated by autophosphorylation. The presence of EPS inhibits autophosphorylation and instead promotes the phosphorylation of a glycosyltransferase in the biosynthetic pathway, thereby stimulating the production of EPS. Thus, EPS production is subject to a positive feedback loop that ties its synthesis to its own concentration. Tyrosine kinase-mediated self-regulation could be a widespread feature of the control of exopolysaccharide production in bacteria.

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Section: Discussionmentioning

confidence: 96%

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

2014

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“…A recent study showed that the concentration of intracellular c-di-GMP in WT P. aeruginosa cells grown in liquid is approximately 11 μM, but can increase to >30 μM when diguanylate cyclase activity is high (26). C-di-GMP levels can be very low in cells expressing phosphodiesterases (27).…”

Section: Discussionmentioning

confidence: 99%

Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ

Baraquet

Harwood

2013

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor FleQ is a bacterial AAA+ ATPase enhancerbinding protein that is the master activator of flagella gene expression in the opportunistic bacterial pathogen Pseudomonas aeruginosa. Homologs of FleQ are present in all Pseudomonas species and in many polarly flagellated gamma proteobacteria. Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger that controls the transition between planktonic and biofilm modes of growth in bacteria in response to diverse environmental signals. C-di-GMP binds to FleQ to dampen its activity, causing down-regulation of flagella gene expression. This action is potentiated in the simultaneous presence of another protein, FleN. We explored the effect of c-di-GMP and FleN on the ATPase activity of FleQ and found that a relatively low concentration of c-di-GMP competitively inhibited FleQ ATPase activity, suggesting that c-di-GMP competes with ATP for binding to the Walker A motif of FleQ. Confirming this, a FleQ Walker A motif mutant failed to bind c-di-GMP. FleN, whose gene is regulated by FleQ, also inhibited FleQ ATPase activity, and FleQ ATPase activity was much more inhibited by c-di-GMP in the presence of FleN than in its absence. These results indicate that FleN and c-di-GMP cooperate to inhibit FleQ activity and, by extension, flagella synthesis in P. aeruginosa. The Walker A motif of FleQ is perfectly conserved, opening up the possibility that other AAA+ ATPases may respond to c-di-GMP.an ubiquitous second messenger in bacteria, where it affects the transition between a motile planktonic lifestyle and an adhesive biofilm lifestyle by binding to various effector proteins to modulate enzymatic activity, protein-protein interactions, transcription, and translation (1-6). One of these effector proteins is FleQ (PA1097), an enhancer-binding protein (EBP) transcription factor from the opportunistic pathogen Pseudomonas aeruginosa.FleQ contains an N-terminal FleQ domain, a central AAA+ ATPase domain, and a C-terminal helix-turn-helix DNA-binding domain. It activates expression of biofilm-related genes, including genes for Pel and Psl exopolysaccharide (EPS) in response to binding of c-di-GMP at an unknown site (7,8). EBPs typically act in conjunction with σ 54 -RNA polymerase; however, FleQ regulates EPS gene expression independent of σ 54 , most likely with σ 70 (8, 9).In addition to regulating genes for biofilm formation, FleQ has a second, better-known role as a σ 54 -dependent master regulator of P. aeruginosa flagella gene expression (9, 10). FleQ activates expression of the two-component regulatory genes fleSR, as well as genes for the assembly of the flagella export apparatus and for the initiation of flagella basal body assembly. FleSR controls genes to complete the basal body-hook structure (9, 11).The regulation of both flagella and biofilm genes is also under the control of a second protein, FleN. Mutations in fleN (PA1454) lead to an up-regulation of flagella gene expression and a smalldown-regulation of biofilm genes (7, 12). The expression ...

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“…In P. aeruginosa PAO1 (a common lab strain), Psl is more important than Pel for biofilm microcolony formation and antibiotic resistance [24]. In addition, Psl also plays an important role in the biofilm formation of mucoid strains [27], and can function as a signal to stimulate biofilm formation [28].…”

Section: Introductionmentioning

confidence: 99%

PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix

et al. 2015

Cell Res

124

126

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Biofilms are surface-associated communities of microorganism embedded in extracellular matrix. Exopolysaccharide is a critical component in the extracellular matrix that maintains biofilm architecture and protects resident biofilm bacteria from antimicrobials and host immune attack. However, self-produced factors that target the matrix exopolysaccharides, are still poorly understood. Here, we show that PslG, a protein involved in the synthesis of a key biofilm matrix exopolysaccharide Psl in Pseudomonas aeruginosa, prevents biofilm formation and disassembles existing biofilms within minutes at nanomolar concentrations when supplied exogenously. The crystal structure of PslG indicates the typical features of an endoglycosidase. PslG mainly disrupts the Psl matrix to disperse bacteria from biofilms. PslG treatment markedly enhances biofilm sensitivity to antibiotics and macrophage cells, resulting in improved biofilm clearance in a mouse implant infection model. Furthermore, PslG shows biofilm inhibition and disassembly activity against a wide range of Pseudomonas species, indicating its great potential in combating biofilm-related complications.

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Self-produced exopolysaccharide is a signal that stimulates biofilm formation inPseudomonas aeruginosa

Cited by 260 publications

References 32 publications

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ

PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix

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