CsgD

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CsgD is a transcription and response regulator protein referenced to as the master modulator of bacterial biofilm development. In E. coli cells, CsgD is tasked with aiding the transition from planktonic cell motility to the stationary phase of biofilm formation, in response to environmental growth factors. [1] A transcription analysis assay (happening in vitro) illustrated a heightened decrease in CsgD's DNA-binding capacity when phosphorylated at A.A. D59 of the protein's primary sequence. [2] Therefore, in the protein's active form (unphosphorylated), CsgD is capable of carrying out its normal functions of regulating curli proteins (fimbria) and producing ECM polysaccharides (cellulose). [3] Following a promoter-lacZ fusion assay of CsgD binding to specific target sites on E. coli's genome, two classes of binding targets were identified: group I genes and group II genes. [4] The group I genes, akin to fliE and yhbT, exhibit repressed transcription following their interaction with CsgD, whilst group II genes, including yccT and adrA, illustrated active functionality. [4] Other group I operons that illustrate repressed transcription include fliE and fliEFGH, for motile flagellum formation. [4] Other group II genes, imperative to the transition towards stationary biofilm development, include csgBA, encoding for curli fimbriae, and adrA, encoding for the synthesis of cyclic diguanylate. [2] [4] In this context, c-di-GMP functions as a bacterial secondary messenger, enhancing the production of extracellular cellulose and impeding flagellum production and rotation. [4]

Related Research Articles

<span class="mw-page-title-main">Pilus</span> A proteinaceous hair-like appendage on the surface of bacteria

A pilus is a hair-like appendage found on the surface of many bacteria and archaea. The terms pilus and fimbria can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All conjugative pili are primarily composed of pilin – fibrous proteins, which are oligomeric.

A sigma factor is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is homologous to archaeal transcription factor B and to eukaryotic factor TFIIB. The specific sigma factor used to initiate transcription of a given gene will vary, depending on the gene and on the environmental signals needed to initiate transcription of that gene. Selection of promoters by RNA polymerase is dependent on the sigma factor that associates with it. They are also found in plant chloroplasts as a part of the bacteria-like plastid-encoded polymerase (PEP).

<span class="mw-page-title-main">Nucleoid</span> Region within a prokaryotic cell containing genetic material

The nucleoid is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a prokaryote is circular, and its length is very large compared to the cell dimensions, so it needs to be compacted in order to fit. In contrast to the nucleus of a eukaryotic cell, it is not surrounded by a nuclear membrane. Instead, the nucleoid forms by condensation and functional arrangement with the help of chromosomal architectural proteins and RNA molecules as well as DNA supercoiling. The length of a genome widely varies and a cell may contain multiple copies of it.

The gene rpoS encodes the sigma factor sigma-38, a 37.8 kD protein in Escherichia coli. Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. rpoS is transcribed in late exponential phase, and RpoS is the primary regulator of stationary phase genes. RpoS is a central regulator of the general stress response and operates in both a retroactive and a proactive manner: it not only allows the cell to survive environmental challenges, but it also prepares the cell for subsequent stresses (cross-protection). The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export proteins, and the diguanylate cyclase, adrA, which indirectly activates cellulose production. The rpoS gene most likely originated in the gammaproteobacteria.

fis

fis is an E. coli gene encoding the Fis protein. The regulation of this gene is more complex than most other genes in the E. coli genome, as Fis is an important protein which regulates expression of other genes. It is supposed that fis is regulated by H-NS, IHF and CRP. It also regulates its own expression (autoregulation). Fis is one of the most abundant DNA binding proteins in Escherichia coli under nutrient-rich growth conditions.

The gene rpoF encodes the sigma factor sigma-28, a protein in Escherichia coli and other species of bacteria. Depending on the bacterial species, this gene may be referred to as sigD or fliA. The protein encoded by this gene has been found to be necessary for flagellum formation.

<span class="mw-page-title-main">OmrA-B RNA</span>

The OmrA-B RNA gene family is a pair of homologous OmpR-regulated small non-coding RNA that was discovered in E. coli during two large-scale screens. OmrA-B is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well. RygB is adjacent to RygA a closely related RNA. These RNAs bind to the Hfq protein and regulate gene expression by antisense binding. They negatively regulate the expression of several genes encoding outer membrane proteins, including cirA, CsgD, fecA, fepA and ompT by binding in the vicinity of the Shine-Dalgarno sequence, suggesting the control of these targets is dependent on Hfq protein and RNase E. Taken together, these data suggest that OmrA-B participates in the regulation of outer membrane composition, responding to environmental conditions.

<span class="mw-page-title-main">RprA RNA</span>

The RprA RNA gene encodes a 106 nucleotide regulatory non-coding RNA. Translational regulation of the stationary phase sigma factor RpoS is mediated by the formation of a double-stranded RNA stem-loop structure in the upstream region of the rpoS messenger RNA, occluding the translation initiation site.

<span class="mw-page-title-main">MicA RNA</span>

The MicA RNA is a small non-coding RNA that was discovered in E. coli during a large scale screen. Expression of SraD is highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well.

The gal operon is a prokaryotic operon, which encodes enzymes necessary for galactose metabolism. Repression of gene expression for this operon works via binding of repressor molecules to two operators. These repressors dimerize, creating a loop in the DNA. The loop as well as hindrance from the external operator prevent RNA polymerase from binding to the promoter, and thus prevent transcription. Additionally, since the metabolism of galactose in the cell is involved in both anabolic and catabolic pathways, a novel regulatory system using two promoters for differential repression has been identified and characterized within the context of the gal operon.

Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

<span class="mw-page-title-main">Flagellar motor switch protein</span>

In molecular biology, the flagellar motor switch protein(Flig) is one of three proteins in certain bacteria coded for by the gene fliG. The other two proteins are FliN coded for by fliN, and FliM coded for by fliM. The protein complex regulates the direction of flagellar rotation and hence controls swimming behaviour. The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour. CheY, the chemotaxis response regulator, is believed to act directly on the switch to induce a switch in the flagellar motor direction of rotation.

The fnr gene of Escherichia coli encodes a transcriptional activator (FNR) which is required for the expression of a number of genes involved in anaerobic respiratory pathways. The FNR protein of E. coli is an oxygen – responsive transcriptional regulator required for the switch from aerobic to anaerobic metabolism.

"Type III mutants, originally frdB, were designated fnr because they were defective in fumarate and nitrate reduction and impaired in their ability to produce gas." - Lambden and Guest, 1976 Journal of General Microbiology97, 145-160

<span class="mw-page-title-main">Histone-like nucleoid-structuring protein</span>

Histone-like nucleoid-structuring protein (H-NS), is one of twelve nucleoid-associated proteins (NAPs) whose main function is the organization of genetic material, including the regulation of gene expression via xenogeneic silencing. H-NS is characterized by an N-terminal domain (NTD) consisting of two dimerization sites, a linker region that is unstructured and a C-terminal domain (CTD) that is responsible for DNA-binding. Though it is a small protein, it provides essential nucleoid compaction and regulation of genes and is highly expressed, functioning as a dimer or multimer. Change in temperature causes H-NS to be dissociated from the DNA duplex, allowing for transcription by RNA polymerase, and in specific regions lead to pathogenic cascades in enterobacteria such as Escherichia coli and the four Shigella species.

<span class="mw-page-title-main">Response regulator</span>

A response regulator is a protein that mediates a cell's response to changes in its environment as part of a two-component regulatory system. Response regulators are coupled to specific histidine kinases which serve as sensors of environmental changes. Response regulators and histidine kinases are two of the most common gene families in bacteria, where two-component signaling systems are very common; they also appear much more rarely in the genomes of some archaea, yeasts, filamentous fungi, and plants. Two-component systems are not found in metazoans.

The gene rpoN encodes the sigma factor sigma-54, a protein in Escherichia coli and other species of bacteria. RpoN antagonizes RpoS sigma factors.

The locus of enterocyte effacement-encoded regulator (Ler) is a regulatory protein that controls bacterial pathogenicity of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC). More specifically, Ler regulates the locus of enterocyte effacement (LEE) pathogenicity island genes, which are responsible for creating intestinal attachment and effacing lesions and subsequent diarrhea: LEE1, LEE2, and LEE3. LEE1, 2, and 3 carry the information necessary for a type III secretion system. The transcript encoding the Ler protein is the open reading frame 1 on the LEE1 operon.

<span class="mw-page-title-main">Curli</span> A proteinaceous extracellular fiber produced by enteric bacteria

The Curli protein is a type of amyloid fiber produced by certain strains of enterobacteria. They are extracellular fibers located on bacteria such as E. coli and Salmonella spp. These fibers serve to promote cell community behavior through biofilm formation in the extracellular matrix. Amyloids are associated with several human neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and prion diseases. The study of curli may help to understand human diseases thought to arise from improper amyloid fiber formation. The curli pili are generally assembled through the extracellular nucleation/precipitation pathway.

<span class="mw-page-title-main">Pho regulon</span>

The Phosphate (Pho) regulon is a regulatory mechanism used for the conservation and management of inorganic phosphate within the cell. It was first discovered in Escherichia coli as an operating system for the bacterial strain, and was later identified in other species. The Pho system is composed of various components including extracellular enzymes and transporters that are capable of phosphate assimilation in addition to extracting inorganic phosphate from organic sources. This is an essential process since phosphate plays an important role in cellular membranes, genetic expression, and metabolism within the cell. Under low nutrient availability, the Pho regulon helps the cell survive and thrive despite a depletion of phosphate within the environment. When this occurs, phosphate starvation-inducible (psi) genes activate other proteins that aid in the transport of inorganic phosphate.

Colanic acid is an exopolysaccharide synthesized by the bacteria Enterobacteriaceae. It is produced as a chemical defense to protect the cell surface, and it assists in the formation of biofilms.

References

  1. Dudin, Omaya; Geiselmann, Johannes; Ogasawara, Hiroshi; Ishihama, Akira; Lacour, Stéphan (February 2014). "Repression of Flagellar Genes in Exponential Phase by CsgD and CpxR, Two Crucial Modulators of Escherichia coli Biofilm Formation". Journal of Bacteriology. 196 (3): 707–715. doi:10.1128/JB.00938-13. ISSN   0021-9193. PMC   3911157 . PMID   24272779.
  2. 1 2 Zakikhany, Katherina; Harrington, Carl R.; Nimtz, Manfred; Hinton, Jay C. D.; Römling, Ute (August 2010). "Unphosphorylated CsgD controls biofilm formation in Salmonella enterica serovar Typhimurium". Molecular Microbiology. 77 (3): 771–86. doi: 10.1111/j.1365-2958.2010.07247.x . PMID   20545866.
  3. Chirwa, Neema T.; Herrington, Muriel B. (2003). "CsgD, a regulator of curli and cellulose synthesis, also regulates serine hydroxymethyltransferase synthesis in Escherichia coli K-12". Microbiology. 149 (2): 525–35. doi: 10.1099/mic.0.25841-0 . PMID   12624214.
  4. 1 2 3 4 5 Ogasawara, Hiroshi; Yamamoto, Kaneyoshi; Ishihama, Akira (May 2011). "Role of the Biofilm Master Regulator CsgD in Cross-Regulation between Biofilm Formation and Flagellar Synthesis▿". Journal of Bacteriology. 193 (10): 2587–2597. doi:10.1128/JB.01468-10. ISSN   0021-9193. PMC   3133154 . PMID   21421764.