Faculty Opinions recommendation of Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation.

2004 ◽  
Author(s):  
Drusilla L Burns
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Cyclic Diguanylate

scholarly journals The LonA Protease Regulates Biofilm Formation, Motility, Virulence, and the Type VI Secretion System in Vibrio cholerae

2016 ◽  
Vol 198 (6) ◽  
pp. 973-985 ◽  
Author(s):  
Andrew Rogers ◽  
Loni Townsley ◽  
Ana L. Gallego-Hernandez ◽  
Sinem Beyhan ◽  
Laura Kwuan ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Secretion System ◽  
Lon Protease ◽  
Human Pathogen ◽  
Type Vi Secretion System ◽  
Cyclic Diguanylate ◽  
Content Type ◽  
Infant Mouse ◽  
Type Vi Secretion

ABSTRACTThe presence of the Lon protease in all three domains of life hints at its biological importance. The prokaryotic Lon protease is responsible not only for degrading abnormal proteins but also for carrying out the proteolytic regulation of specific protein targets. Posttranslational regulation by Lon is known to affect a variety of physiological traits in many bacteria, including biofilm formation, motility, and virulence. Here, we identify the regulatory roles of LonA in the human pathogenVibrio cholerae. We determined that the absence of LonA adversely affects biofilm formation, increases swimming motility, and influences intracellular levels of cyclic diguanylate. Whole-genome expression analysis revealed that the message abundance of genes involved in biofilm formation was decreased but that the message abundances of those involved in virulence and the type VI secretion system were increased in alonAmutant compared to the wild type. We further demonstrated that alonAmutant displays an increase in type VI secretion system activity and is markedly defective in colonization of the infant mouse. These findings suggest that LonA plays a critical role in the environmental survival and virulence ofV. cholerae.IMPORTANCEBacteria utilize intracellular proteases to degrade damaged proteins and adapt to changing environments. The Lon protease has been shown to be important for environmental adaptation and plays a crucial role in regulating the motility, biofilm formation, and virulence of numerous plant and animal pathogens. We find that LonA of the human pathogenV. choleraeis in line with this trend, as the deletion of LonA leads to hypermotility and defects in both biofilm formation and colonization of the infant mouse. In addition, we show that LonA regulates levels of cyclic diguanylate and the type VI secretion system. Our observations add to the known regulatory repertoire of the Lon protease and the current understanding ofV. choleraephysiology.

scholarly journals Cyclic Diguanylate Regulates Vibrio cholerae Virulence Gene Expression

2005 ◽  
Vol 73 (9) ◽  
pp. 5873-5882 ◽  
Author(s):  
Anna D. Tischler ◽  
Andrew Camilli
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Single Amino Acid ◽  
Transcriptional Level ◽  
Phosphodiesterase Activity ◽  
High Concentration ◽  
Cyclic Diguanylate ◽  
Virulence Gene Expression ◽  
Infant Mouse

ABSTRACT The cyclic dinucleotide second messenger cyclic diguanylate (c-diGMP) has been implicated in regulation of cell surface properties in several bacterial species, including Vibrio cholerae. Expression of genes required for V. cholerae biofilm formation is activated by an increased intracellular c-diGMP concentration. The response regulator VieA, which contains a domain responsible for degradation of c-diGMP, is required to maintain a low concentration of c-diGMP and repress biofilm formation. The VieSAB three-component signal transduction system was, however, originally identified as a regulator of ctxAB, the genes encoding cholera toxin (CT). Here we show that the c-diGMP phosphodiesterase activity of VieA is required to enhance CT production. This regulation occurred at the transcriptional level, and ectopically altering the c-diGMP concentration by expression of diguanylate cyclase or phosphodiesterase enzymes also affected ctxAB transcription. The c-diGMP phosphodiesterase activity of VieA was also required for maximal transcription toxT but did not influence the activity of ToxR or expression of TcpP. Finally, a single amino acid substitution in VieA that increases the intracellular c-diGMP concentration led to attenuation in the infant mouse model of cholera. Since virulence genes including toxT and ctxA are repressed by a high concentration of c-diGMP, while biofilm genes are activated, we suggest that c-diGMP signaling is important for the transition of V. cholerae from the environment to the host.

scholarly journals Functional Specialization in Vibrio cholerae Diguanylate Cyclases: Distinct Modes of Motility Suppression and c-di-GMP Production

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
David Zamorano-Sánchez ◽  
Wujing Xian ◽  
Calvin K. Lee ◽  
Mauro Salinas ◽  
Wiriya Thongsomboon ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Cell Tracking ◽  
Regulation Mechanism ◽  
Cyclic Diguanylate ◽  
Content Type ◽  
Bacterial Signaling ◽  
Diguanylate Cyclases ◽  
Motility Regulation ◽  
Gmp Production

ABSTRACT Vibrio cholerae biofilm formation and associated motility suppression are correlated with increased concentrations of cyclic diguanylate monophosphate (c-di-GMP), which are in turn driven by increased levels and/or activity of diguanylate cyclases (DGCs). To further our understanding of how c-di-GMP modulators in V. cholerae individually and collectively influence motility with cellular resolution, we determined how DGCs CdgD and CdgH impact intracellular c-di-GMP levels, motility, and biofilm formation. Our results indicated that CdgH strongly influences swim speed distributions; cells in which cdgH was deleted had higher average swim speeds than wild-type cells. Furthermore, our results suggest that CdgD, rather than CdgH, is the dominant DGC responsible for postattachment c-di-GMP production in biofilms. Lipopolysaccharide (LPS) biosynthesis genes were found to be extragenic bypass suppressors of the motility phenotypes of strains ΔcdgD and ΔcdgH. We compared the motility regulation mechanism of the DGCs with that of Gmd, an LPS O-antigen biosynthesis protein, and discovered that comodulation of c-di-GMP levels by these motility effectors can be positively or negatively cooperative rather than simply additive. Taken together, these results suggest that different environmental and metabolic inputs orchestrate DGC responses of V. cholerae via c-di-GMP production and motility modulation. IMPORTANCE Cyclic diguanylate monophosphate (c-di-GMP) is a broadly conserved bacterial signaling molecule that affects motility, biofilm formation, and virulence. Although it has been known that high intracellular concentrations of c-di-GMP correlate with motility suppression and biofilm formation, how the 53 predicted c-di-GMP modulators in Vibrio cholerae collectively influence motility is not understood in detail. Here we used a combination of plate assays and single-cell tracking methods to correlate motility and biofilm formation outcomes with specific enzymes involved in c-di-GMP synthesis in Vibrio cholerae, the causative agent of the disease cholera.

scholarly journals The bioactive lipid (S)-sebastenoic acid impacts motility and dispersion in Vibrio cholerae

2018 ◽  
Vol 96 (2) ◽  
pp. 196-203
Author(s):  
Christopher J.A. Warner ◽  
Mauro Salinas ◽  
David Zamorano-Sánchez ◽  
Walter M. Bray ◽  
R. Scott Lokey ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
High Throughput ◽  
Biofilm Formation ◽  
Healthcare Systems ◽  
Bacterial Motility ◽  
Cyclic Diguanylate ◽  
Gram Negative ◽  
Chemical Genetic ◽  
Genetic Probes ◽  
Screening Platform

Although Gram-negative bacterial pathogens continue to impart a substantial burden on global healthcare systems, much remains to be understood about aspects of basic physiology in these organisms. In recent years, cyclic-diguanylate (c-di-GMP) has emerged as a key regulator of a number of important processes related to pathogenicity, including biofilm formation, motility, and virulence. In an effort to discover chemical genetic probes for studying Vibrio cholerae we have developed a new motility-based high-throughput screen to identify compounds that modulate c-di-GMP levels. Using this new screening platform, we tested a library of microbially derived marine natural products extracts, leading to the discovery of the bioactive lipid (S)-sebastenoic acid. The evaluation of the effect of this new compound on bacterial motility, vpsL expression, and biofilm formation implied that (S)-sebastenoic acid may alter phenotypes associated to c-di-GMP signaling in V. cholerae.

scholarly journals Specific Control of Pseudomonas aeruginosa Surface-Associated Behaviors by Two c-di-GMP Diguanylate Cyclases

mBio ◽  
2010 ◽  
Vol 1 (4) ◽  
Author(s):  
Judith H. Merritt ◽  
Dae-Gon Ha ◽  
Kimberly N. Cowles ◽  
Wenyun Lu ◽  
Diana K. Morales ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Extracellular Polysaccharide ◽  
Diguanylate Cyclase ◽  
Flagellar Motility ◽  
Critical Question ◽  
Cyclic Diguanylate ◽  
Critical Signal ◽  
Content Type ◽  
Wide Range

ABSTRACT The signaling nucleotide cyclic diguanylate (c-di-GMP) regulates the transition between motile and sessile growth in a wide range of bacteria. Understanding how microbes control c-di-GMP metabolism to activate specific pathways is complicated by the apparent multifold redundancy of enzymes that synthesize and degrade this dinucleotide, and several models have been proposed to explain how bacteria coordinate the actions of these many enzymes. Here we report the identification of a diguanylate cyclase (DGC), RoeA, of Pseudomonas aeruginosa that promotes the production of extracellular polysaccharide (EPS) and contributes to biofilm formation, that is, the transition from planktonic to surface-dwelling cells. Our studies reveal that RoeA and the previously described DGC SadC make distinct contributions to biofilm formation, controlling polysaccharide production and flagellar motility, respectively. Measurement of total cellular levels of c-di-GMP in ∆roeA and ∆sadC mutants in two different genetic backgrounds revealed no correlation between levels of c-di-GMP and the observed phenotypic output with regard to swarming motility and EPS production. Our data strongly argue against a model wherein changes in total levels of c-di-GMP can account for the specific surface-related phenotypes of P. aeruginosa. IMPORTANCE A critical question in the study of cyclic diguanylate (c-di-GMP) signaling is how the bacterial cell integrates contributions of multiple c-di-GMP-metabolizing enzymes to mediate its cognate functional outputs. One leading model suggests that the effects of c-di-GMP must, in part, be localized subcellularly. The data presented here show that the phenotypes controlled by two different diguanylate cyclase (DGC) enzymes have discrete outputs despite the same total level of c-di-GMP. These data support and extend the model in which localized c-di-GMP signaling likely contributes to coordination of the action of the multiple proteins involved in the synthesis, degradation, and/or binding of this critical signal.

scholarly journals Indole Acts as an Extracellular Cue Regulating Gene Expression in Vibrio cholerae

2009 ◽  
Vol 191 (11) ◽  
pp. 3504-3516 ◽  
Author(s):  
Ryan S. Mueller ◽  
Sinem Beyhan ◽  
Simran G. Saini ◽  
Fitnat H. Yildiz ◽  
Douglas H. Bartlett
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Signal Molecule ◽  
Control Of Gene Expression ◽  
Protozoan Grazing ◽  
Extracellular Signal ◽  
Grazing Resistance ◽  
Indole Signaling

ABSTRACT Indole has been proposed to act as an extracellular signal molecule influencing biofilm formation in a range of bacteria. For this study, the role of indole in Vibrio cholerae biofilm formation was examined. It was shown that indole activates genes involved in vibrio polysaccharide (VPS) production, which is essential for V. cholerae biofilm formation. In addition to activating these genes, it was determined using microarrays that indole influences the expression of many other genes, including those involved in motility, protozoan grazing resistance, iron utilization, and ion transport. A transposon mutagenesis screen revealed additional components of the indole-VPS regulatory circuitry. The indole signaling cascade includes the DksA protein along with known regulators of VPS production, VpsR and CdgA. A working model is presented in which global control of gene expression by indole is coordinated through σ54 and associated transcriptional regulators.

scholarly journals Identification and Characterization of OscR, a Transcriptional Regulator Involved in Osmolarity Adaptation in Vibrio cholerae

2009 ◽  
Vol 191 (13) ◽  
pp. 4082-4096 ◽  
Author(s):  
Nicholas J. Shikuma ◽  
Fitnat H. Yildiz
Keyword(s):  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Transcriptional Regulator ◽  
Dependent Manner ◽  
Genome Wide ◽  
Low Salt ◽  
Adaptation Response ◽  
Matrix Production ◽  
Identification And Characterization

ABSTRACT Vibrio cholerae is a facultative human pathogen. In its aquatic habitat and as it passes through the digestive tract, V. cholerae must cope with fluctuations in salinity. We analyzed the genome-wide transcriptional profile of V. cholerae grown at different NaCl concentrations and determined that the expression of compatible solute biosynthesis and transporter genes, virulence genes, and genes involved in adhesion and biofilm formation is differentially regulated. We determined that salinity modulates biofilm formation, and this response was mediated through the transcriptional regulators VpsR and VpsT. Additionally, a transcriptional regulator controlling an osmolarity adaptation response was identified. This regulator, OscR (osmolarity controlled regulator), was found to modulate the transcription of genes involved in biofilm matrix production and motility in a salinity-dependent manner. oscR mutants were less motile and exhibited enhanced biofilm formation only under low-salt conditions.

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