User talk:Praphulla249
Agr Operon
[edit]
The expression of virulence factors and surface proteins in
the human pathogen Staphylococcus aureus is regulated by accessory gene regulator(agr).
Quorum sensing system plays a vital role in regulating the synthesis of virulence factors in Staphylococcus aureus,which in turn is controlled by the agr operon.
The agr system is highly conserved throughout the Staphylococcus family.
The agr locus has two divergent transcription units,RNAII and RNAIII.The RNAII transcript,driven by P2 promoter encodes quorum sensing system and consists of four open reading frames AgrB, AgrC,AgrD and AgrA.Wherein AgrA plays a major role in activating the agr operon. The RNAIII transcript,driven by P3 promoter regulates the
expression of other genes related to quorum sensing.It results in increased production of virulence factors
and decreased expression of surface proteins[1] .
Not only does the agr operon regulate the expression of virulence factors but also the expression of its own genes.The system has a positive feedback loop which ascertains the expression of targeted genes at a certain threshold level of bacterial cell density.
Structure
[edit]The agr operon contains two transcription units RNAII and RNAIII. RNA II, driven by P2 promoter,is a polycistronic mRNA encoding four proteins [2] :
• agrB : modifies and secretes AIP from the cell
• agrD : pro-autoinducing peptide( signalling molecule)
• agrC : membrane bound protein serves as receptor
• agrA : DNA binding response regulator
Significance
[edit]Quorum sensing systems in Straphylococcus aureus are key virulence reguators.They depend on small signalling molecules, known as autoinducers, produced and detected by the bacteria.At low cell densities the organism expresses proteins for attachment and colonization,whereas at high cell densities it starts overexpressing the toxins through the expression of agr operon. Based on the concentration of the autoinducing peptides,the agr operon transduces the signal that the required concentration of cell density is attained ,which in turn positively regulates the operon resulting in high expression of virulence factors.
Mechanism
[edit]AgrD codes for a pro-peptide; AgrB is an integral membrane protein which modifies the AIPS,resulting in an octapeptide autoinducing peptide (AIP) and secretes it out of the cell. Once the transmembrane receptor domain of AgrC is bound by AIP, it will phosphorylate AgrA which further activates the two promoters P2 and P3 . RNA III, driven by P3 promoter, acts as a regulatory factor to activate numerous toxin production genes and encode for β-hemolysin. Activated AgrA increases the expression of RNAII which leads to production of sufficient number of AIPs indicating that the cell density has reached a threshold level[3] .
Regulation
[edit]
The synthesis of RNAIII is regulated by two Staphylococcal quorum sensing systems SQS 1 and SQS 2. SQS 1
composes a RNAIII-activating protein (RAP) and a target of RNAIII-activating
protein (TRAP) which is membrane associated. As cell density increases, RAP is secreted out.
Once a sufficient concentration of RAP is attained, it will induce the histidine
phosphorylation of TRAP, leading to the synthesis of SQS 2, which encodes the products of agr system.The activation of agr system leads to production of
RNAII. After the activation of agr system, phosphorylation of AgrC is
induced by secreted AIP, followed by the production of RNAIII[4].
Other parallel quorum sensing circuits also regulate the expression of agr locus[5] :
- Sar : elevates the levels of agr transcription
- Srr : inhibits the synthesis of RNAIII
- RIP : blocks RAP
- Repressor of Toxins (ROT) : prevents binding of RAP to TRAP
Eukaryotic homologue
[edit]Molecular mechanisms that drive the quorum signalling systems are present even in the eukaryotes.Some social insects like bees and ants use these systems for communication. Many higher social organisms are believed to use chemical signalling pathways that are quite analogous to the cell to cell communication systems in prokaryotes.
References
[edit]- ^ Jonathan Reynolds, Sivaramesh Wigneshwerara(Oct 2011) Molecular Insights into the Control of Transcription Initiation at the Staphylococcus aureus agr operon Journal of Molecular Biology 412(5): 862-881 [1]
- ^ Christopher M.Waters and Bonnie L. Bassler(2005) Quorum Sensing: Cell-to-Cell Communication in Bacteria Annual Review of Cell and Developmental Biology (21):319–46. DOI=10.1146/ annurev.cellbio.21.012704.131001 PMID:16212498
- ^ Sara Jabbari · John R. King Adrian J. Koerber · Paul Williams(2010) Mathematical modelling of the agr operon in Staphylococcus aureusJournal of Mathematical Biology 61:17–54. DOI=10.1007/s00285-009-0291-6 PMID:19688348
- ^ Moshe Korem,Yael Gov, Madanahally D. Kiran, and Naomi Balaban(Oct 2005) Transcriptional Profiling of Target of RNAIII-Activating Protein, a Master Regulator of Staphylococcal Virulence Infection and Immunity 73(10). DOI=10.1128/IAI.73.10.6220-6228.2005 PMID:1230921
- ^ Jeremy M. Yarwood ,Patrick M. Schlievert(December 2003) Quorum sensing in Staphylococcus infectionsJournal of Clinical Investigation 112 (11):1620–1625.DOI: 10.1172/JCI200320442 PMID: 281656