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Streptococcus Pyogenes bacteria is a world-wide known human pathogen, belongs to the Group A Streptococcus, GAS. It is Gram-positive, non-motile, and spherical in form which grows in long ironss or braces. S.pyogenes is distinguished from the other Streptococci by the presence of the Lance Field Group A saccharide found on its cell wall and it produces big zone of beta-hemolysis ( hemoglobin released when the red blood cells are wholly disrupted ) when grown on a home base enriched in blood agar. Therefore it is known as the Group A ( beta-haemolytic ) Streptococcus ( GAS ) .

Group A Streptococcal Infections is chiefly caused by the S.pyogenes ensuing in badness and it is documented throughout the universe in all sexes, races and age group. Diseases caused by GAS scopes from mild upper respiratory tract- sore throat or impetigo but in utmost instances, it will take to invasive diseases- cellulitis, bacteriemia, necrotizing installations and toxic daze syndrome ( TSS ) .

In bacteriums cell envelope, it is deemed to be great importance as the critical point for interaction between the bacteria and it environment. Bacterial cell envelope proteins carry out assortment of of import maps such as adhesion, alimentary acquisition and legion sum of interaction with the host defense mechanisms ( Lain C. Sutcliffe and Dean J Harrington, 2002 ) .

In Gram-positive bacterium, it lacks a recollective outer membrane and therefore, it had evolved a mechanism for retaining proteins within their cell envelopes, including covalent linkage to the peptidoglycan and non-covalent binding to teichoic acids and other cell polymers. aa‚¬ ”

These bacterial lipoproteins have their N-terminal modified with N-Acyl Diacyl Glyceryl Group and in another possible farther measure whereby an extra fatso acid is amide linked to the free amino end point which does non look to happen in the low G+C gm positive bacteriums ( Lain C. Sutcliffe and Dean J Harrington, 2002 ) .

Bacteria lipid alteration enables it to expeditiously transport out their of import maps between the cell wall and the environment ( Braun et al, 1993 ) . Bacterial lipid alteration is critical for its viability and it is omnipresent in and alone to bacteriums.

Bacterial Lipoproteins

Bacterial cell envelope proteins carry out legion sums of of import maps between the bacteria and the environment, chiefly the interaction between the host and host pathogen.

In Gram Positive due to miss of outer recollective membrane, they have established their ain specialized mechanisms for retaining their ain lipoprotein in their outer membrane. Among the mechanisms established in Gram positive bacteria, membrane anchoring of bacterial lipoproteins ( Lpps ) by covalent N-terminal lipidation is important ( Braun & A ; Wu, 1994 ; Sutcliffe & A ; Russell, 1995 ) .

Lipoproteins lipid alteration was attained through by covalently adding a diacyglycerol to the invariant cysteine residue in the lipoprotein signal peptide as was described in the Braunaa‚¬a„?s lipoprotein in Escherichia coli ( Braun and Wu, 1994 ) .

Lpps performs broad scope of critical maps such as substrate binding proteins ( SBPs ) in ABC transporter system ; in antibiotic opposition ; in cell signalling ; in protein export and folding ; in monogenesis and sprouting ; in junction and assorted other maps ( Sutcliffe & A ; Russell, 1995 ) .

Therefore, the lipoproteins of Gram-positive bacteriums have been proposed to be functionally tantamount as that of Gram-negative bacteriums. It was straight compared and confirmed by the fact that SBPs of ATP adhering are typically lipoprotein ( Nielsen and Lampen, 1982 ) .

Translocation across cellular membrane

In order to make their site of map, huge proportion of freshly synthesised proteins need to translocate to outer cell memebrane. This is done chiefly via the general secretory ( Sec ) tract and Tat ( duplicate arginine protein conveyance ) system. The difference between the two systems lies in the protein conformation either folded or unfolded.

Prokaryotes proteins targeted to the periplasm and to outer cell membrane are normally transported across cytoplasmatic membrane by the Sec tract ( Pugsley, 1993 ) . Therefore, the Sec tract is the prevailing path of transit of proteins across the cytoplasmatic membrane among the two distinguishable tracts ( Driessen and Nouwen, 2008 ) . In Sec tract, the proteins with unfolded conformation have to synthesised with N-terminal sequence which will excised at a ulterior phase during the exportation via a signal protease situated on the periplasmic face of the membrane. There has been findings in which some of the putative lipoproteins are exported via SecA2 accessary pathway across the cytoplasmatic membrane in unfolded province ( Braun and Wu, 1944 ; Froderberg, 2004 ) .

In Tat system, proteins with folded conformation, even oligomeric proteins are transported to periplasmic membrane. Under the Tat system, protein signal sequence remarkably long contains consensuses S/T-R-R-x-F-L-K in which arginine residues is invariant and frequently adhere to redox cofactors on the cytosol ( Berks, 1996 ; Santini et al. , 1998 ) . Lipoproteins precursor s exported through Tat system in to the full folded conformation were confirmed during an analysis of dimethyl sulphoxide ( Dms ) reductase in Gram-negative bacteriums ( Gralnick, J.A. et Al ) .

This indicates that Tat system is a mechanism which is basically different from the Sec tract and requires the proteins to be folded before they cross the cellular membrane.

Proteins destined for lipidation contains a motive in their signal peptide, lipobox which forwards them to lipoprotein biosynthesis machinery after exportation via either Sec tract or Tat system. Surveies chiefly based on E.coli, indicates that all freshly synthesized lipoproteins are transported via Sec tract in an unfolded conformation across the cytoplasmatic membrane ( Braun and Wu, 1994 ; Froderberg, 2004 ) .

Lipoprotein Biogenesis

To achieve their full fledged map, the freshly synthesised protein exported across the cytoplasmatic membrane via the Sec tract or Tat system will be channelled to the lipoprotein biosynthesis machinery. This imparting procedure will be guided by the conserved motive ( lipobox ) in the proteins signal peptides to the machinery. Lipoprotein biogenesis tract was good characterized in the surveies of E.coli ( Braun and Wu, 1994 ) .

Figure 2: Type I and Type II signal peptides via Sec and Tat Dependent Transport ( a ) General Secretory Pathway, ( B ) Cheapness System

Type I and Type II signal peptides composed of three distinguishable sections, a positively charged amino-terminal N, a cardinal, H- ( hydrophobic ) part and a more polar carboxy terminal C- ( cleavage part ) ( von Heijne,1985 ) .Within type I signal peptide, it sustains a acknowledgment motive ( A-X-A, where Ten can be any aminic acid ) . In the instance of Type II signal peptide, it contains the acknowledgment motif sequence of ( L-3- [ A/S/T ] -2- [ G/A ] — 1-C+1 ) and its cleavage site frequently referred as lipoprotein aa‚¬E?lipoboxaa‚¬a„? . It is distinguishable in its manner that it has conserved SRRXFLK sequence between N-region and H-region ( Petit, C.M et Al ) , within which the twin arginine ( RR ) motive is about perfectly conserved. The common residue among all the bacterial lipoproteins is the conserved cysteine +1 of the Type 2 signal peptide lipobox ( L-3- [ A/S/T ] -2- [ G/A ] — 1-C+1 ) .

Bacterial lipoprotein biogenesis word picture in E.coli done via a distinguishable and conserved tract is alone to procaryotes ( Braun, V. , and H.C.Wu, 1993 ) .Once the protein is exported across the cellular membrane with the counsel of the signal peptides via Sec or Tat dependent system, the conserved cysteine residue within the lipobox of the signal peptide is modified with a diacyglycerol group attached through a thioether linkage. The above whole reaction is catalyzed by the enzyme prolipoprotein diacylglycerol transferase ( Lgt ) , utilizing phospholipid substrates ( Sankaran et al. , 1995 ; Qi et al. , 1995 ) .

Once after the conserved residue gets lipdated, the signal peptide is cleaved within the lipobox by a specific lipoprotein signal protease II ( Lsp ) , enzyme to let go of the lipidated cysteine as the N-terminal for the mature bacterial lipoprotein ( Braun & A ; Wu, 1994 ; Sankaran & A ; Wu, 1995 ) . The signal protease II requires diacylglycerol alteration prior to cleavage and this identifies that diacylglycerol alteration must done before the cleavage procedure by Lsp, enzyme ( Hussain, M et Al, 1980 ; Dev, I.K. and Ray, P.H.1984 ) . Above mentioned stairss for lipidation of Gram-positive bacteriums, it was confirmed to be critical and sufficient.

The last alteration of the lipoprotein in the biosynthesis tract would be the lipid alteration of the lipoprotein by a fatty acylation of the amino group of the N-terminal diacylglycerol modified Cys to organize N-acyl diacylglycerol Cysteine.

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