scholarly journals Quantitative input-output dynamics of a c-di-GMP signal-transduction cascade in Vibrio cholerae

2021 ◽  
Author(s):  
Andrew A Bridges ◽  
Joseph A Prentice ◽  
Chenyi Fei ◽  
Ned S Wingreen ◽  
Bonnie L Bassler
Keyword(s):  
Vibrio Cholerae ◽  
Signal Transmission ◽  
Sensory Information ◽  
Bacterial Biofilms ◽  
Input Output ◽  
Cyclic Diguanylate ◽  
Environmental Threats ◽  
Signal Transduction Cascade ◽  
Local Signaling ◽  
Messenger Molecule

Bacterial biofilms are multicellular communities that collectively overcome environmental threats and clinical treatments. To regulate the biofilm lifecycle, bacteria commonly transduce sensory information via the second-messenger molecule cyclic diguanylate (c-di-GMP). Using experimental and modeling approaches, we quantitatively capture c-di-GMP signal transmission via the bifunctional polyamine receptor NspS-MbaA, from ligand binding to output, in the pathogen Vibrio cholerae. Upon binding of norspermidine or spermidine, NspS-MbaA synthesizes or degrades c-di-GMP, respectively, which in turn, drives alterations specifically to biofilm gene expression. A longstanding question is how output specificity is achieved via c-di-GMP, a diffusible molecule that regulates dozens of effectors. We show that NspS-MbaA signals locally to specific effectors, sensitizing V. cholerae to polyamines. However, local signaling is not required for specificity, as changes to global cytoplasmic c-di-GMP levels can selectively regulate biofilm genes. This work establishes the input-output dynamics underlying c-di-GMP signaling, which could be useful for developing bacterial manipulation strategies.

scholarly journals Discrete escape responses are generated by neuropeptide-mediated circuit logic

2020 ◽  
Author(s):  
Bibi Nusreen Imambocus ◽  
Annika Wittich ◽  
Federico Tenedini ◽  
Fangmin Zhou ◽  
Chun Hu ◽  
...  
Keyword(s):  
Escape Behavior ◽  
Sensory Information ◽  
Environmental Threats ◽  
Order Processing ◽  
Relaxin Family ◽  
Escape Responses ◽  
Discrete Domains ◽  
Light Avoidance ◽  
Escape Behaviors ◽  
Selection Of

AbstractAnimals display a plethora of escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximize chances of survival. We uncovered a somatosensory network in Drosophila larvae that encodes two escape behaviors through input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of the same neuromodulatory hub neurons. These gate harsh touch responses via short Neuropeptide F, but noxious light avoidance via compartmentalized, acute Insulin-like peptide 7 action and cognate Relaxin-family receptor signaling in connected downstream neurons. Peptidergic hub neurons can thus act as central circuit elements for first order processing of converging sensory inputs to gate specific escape responses.One Sentence SummaryCompartment-specific neuropeptide action regulates sensory information processing to elicit discrete escape behavior in Drosophila larvae.

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 Hypothalamic circuits for mechanically-evoked defensive attack

2020 ◽  
Author(s):  
Peng Cao ◽  
Zhiyong Xie ◽  
Huating Gu ◽  
Congping Shang ◽  
Xinyu Cheng ◽  
...  
Keyword(s):  
Critical Role ◽  
Sensory Information ◽  
Mechanical Force ◽  
Hypothalamic Nucleus ◽  
Mechanical Stimuli ◽  
Neural Signals ◽  
Environmental Threats ◽  
Efferent Pathway ◽  
Defensive Behaviors ◽  
The Brain

Abstract The innate defensive behaviors triggered by environmental threats play a critical role in animal survival. Among these behaviors, defensive attack physically toward threatening target (e.g. predator) is the last line of defense to struggle for survival. How the brain transforms threat-relevant sensory information into the action of defensive attack remains poorly understood. We found that noxious mechanical force in an inescapable context was a key stimulus to trigger defensive attack in laboratory mice. The mechanically-evoked defensive attack was abrogated by photoinhibition of vGAT+ neurons in the anterior hypothalamic nucleus (AHN). The AHN vGAT+ neurons encoded the intensity of mechanical force and were innervated by brain areas related to pain and attack. Activation of these neurons triggered biting attack toward predator, while suppressing other ongoing behaviors. The efferent pathway from AHN vGAT+ neurons to the periaqueductal gray was both sufficient and necessary for mechanically-evoked defensive attack. Together, these data revealed a GABAergic brain circuit engaged in converting noxious mechanical stimuli to neural signals that provoke defensive attack in mice.

scholarly journals Cyclic di-GMP Regulates TfoY inVibrio choleraeTo Control Motility by both Transcriptional and Posttranscriptional Mechanisms

2018 ◽  
Vol 200 (7) ◽  
Author(s):  
Benjamin R. Pursley ◽  
Michael M. Maiden ◽  
Meng-Lun Hsieh ◽  
Nicolas L. Fernandez ◽  
Geoffrey B. Severin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Second Messenger ◽  
Bacterial Motility ◽  
Content Type ◽  
Intracellular Concentrations ◽  
Messenger Molecule

ABSTRACT3′,5′-Cyclic diguanylic acid (c-di-GMP) is a bacterial second messenger molecule that is a key global regulator inVibrio cholerae, but the molecular mechanisms by which this molecule regulates downstream phenotypes have not been fully characterized. One such regulatory factor that may respond to c-di-GMP is the Vc2 c-di-GMP-binding riboswitch that is hypothesized to control the expression of the downstream putative transcription factor TfoY. Although much is known about the physical and structural properties of the Vc2 riboswitch aptamer, the nature of its expression and function inV. choleraehas not been investigated. Here, we show that Vc2 functions as an off switch to inhibit TfoY production at intermediate and high concentrations of c-di-GMP. At low c-di-GMP concentrations, TfoY production is induced to stimulate dispersive motility. We also observed increased transcription oftfoYat high intracellular concentrations of c-di-GMP, but this induction is independent of the Vc2 riboswitch and occurs via transcriptional control of promoters upstream oftfoYby the previously identified c-di-GMP dependent transcription factor VpsR. Our results show that TfoY is induced by c-di-GMP at both low and high intracellular concentrations of c-di-GMP via posttranscriptional and transcriptional mechanisms, respectively. This regulation contributes to the formation of three distinct c-di-GMP signaling states inV. cholerae.IMPORTANCEThe bacterial pathogenVibrio choleraemust transition between life in aquatic environmental reservoirs and life in the gastrointestinal tract. Biofilm formation and bacterial motility, and their control by the second messenger molecule c-di-GMP, play integral roles in this adaptation. Here, we define the third major mechanism by which c-di-GMP controls bacterial motility. This pathway utilizes a noncoding RNA element known as a riboswitch that, when bound to c-di-GMP, inhibits the expression of the transcription factor TfoY. TfoY production switchesV. choleraemotility from a dense to a dispersive state. Our results suggest that the c-di-GMP signaling network ofV. choleraecan exist in at least three distinct states to regulate biofilm formation and motility.

scholarly journals Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae

2014 ◽  
Vol 82 (7) ◽  
pp. 3002-3014 ◽  
Author(s):  
Benjamin J. Koestler ◽  
Christopher M. Waters
Keyword(s):  
Small Intestine ◽  
Bile Acids ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Intracellular Concentration ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Proximal Small Intestine ◽  
Ph Buffer ◽  
Messenger Molecule

ABSTRACTVibrio choleraeis a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host.V. choleraeemploys the second messenger molecule 3′,5′-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors inV. cholerae, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP inV. cholerae. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose thatV. choleraesenses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.

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.

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