Second Messenger Regulation of Biofilm Formation: Breakthroughs in Understanding c-di-GMP Effector Systems

Boyd, Chelsea D.; O’Toole, George A.

doi:10.1146/annurev-cellbio-101011-155705

Cited by 207 publications

(189 citation statements)

References 117 publications

(245 reference statements)

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…Thus, we found a novel mechanism of control of bacterial c-di-AMP synthesis via RadA-DisA interaction in M. smegmatis. In recent years, accumulating evidence has shown that cyclic dinucleotides widely function as second messengers that control multiple microbial phenotypes and physiological characteristics (4,5,(25)(26)(27)(28). Compared with the clearly characterized functions for c-di-GMP in many bacteria (4,5,28), much less is known about the control of c-di-AMP synthesis and its effects on bacterial growth.…”

Section: Discussionmentioning

confidence: 99%

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Zhang

2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:Little is known about the control of cyclic di-AMP synthesis in bacteria. Results: RadA targets DisA to inhibit its cyclic di-AMP synthesis activity that regulates mycobacterial growth. Conclusion:We report a novel mechanism of control of c-di-AMP synthesis and its effects on bacterial growth in Mycobacterium smegmatis. Significance: These findings enhance our understanding of c-di-AMP synthesis control and its roles in bacteria.

show abstract

Section: Discussionmentioning

confidence: 99%

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Zhang

2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The cAMP signaling pathway also interacts with the c-di-GMP pathway, playing a role in regulating V. cholerae biofilm formation (472). The c-di-GMP signaling mechanism represents a unifying principle governing the microbial switch from a planktonic to a sessile lifestyle (514,515). …”

Section: Centralized Regulation By Second Messengersmentioning

confidence: 99%

Microbial Surface Colonization and Biofilm Development in Marine Environments

Dang

Lovell

2016

Microbiol Mol Biol Rev

835

636

View full text Add to dashboard Cite

SUMMARYBiotic and abiotic surfaces in marine waters are rapidly colonized by microorganisms. Surface colonization and subsequent biofilm formation and development provide numerous advantages to these organisms and support critical ecological and biogeochemical functions in the changing marine environment. Microbial surface association also contributes to deleterious effects such as biofouling, biocorrosion, and the persistence and transmission of harmful or pathogenic microorganisms and their genetic determinants. The processes and mechanisms of colonization as well as key players among the surface-associated microbiota have been studied for several decades. Accumulating evidence indicates that specific cell-surface, cell-cell, and interpopulation interactions shape the composition, structure, spatiotemporal dynamics, and functions of surface-associated microbial communities. Several key microbial processes and mechanisms, including (i) surface, population, and community sensing and signaling, (ii) intraspecies and interspecies communication and interaction, and (iii) the regulatory balance between cooperation and competition, have been identified as critical for the microbial surface association lifestyle. In this review, recent progress in the study of marine microbial surface colonization and biofilm development is synthesized and discussed. Major gaps in our knowledge remain. We pose questions for targeted investigation of surface-specific community-level microbial features, answers to which would advance our understanding of surface-associated microbial community ecology and the biogeochemical functions of these communities at levels from molecular mechanistic details through systems biological integration.

show abstract

“…transcription factor | σ 54 | AAA+ protein | competitive inhibition B is-(3′-5′)-cyclic diguanosine monophosphate (c-di-GMP) is 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)(2)(3)(4)(5)(6). One of these effector proteins is FleQ (PA1097), an enhancer-binding protein (EBP) transcription factor from the opportunistic pathogen Pseudomonas aeruginosa.…”

mentioning

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.

164

192

View full text Add to dashboard Cite

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 ...

show abstract

Second Messenger Regulation of Biofilm Formation: Breakthroughs in Understanding c-di-GMP Effector Systems

Cited by 207 publications

References 117 publications

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Microbial Surface Colonization and Biofilm Development in Marine Environments

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

Contact Info

Product

Resources

About