Sepsis major enzymatic reactions. the first reaction is carried

Sepsis is a life-threatening condition caused by an overwhelming host response to infection which can lead to multi-organ failure and death ().  It is the second leading cause of death in noncanonical intensive care units (). In general, infection is caused by bacteria but it is also from additional microorganisms like viruses, fungi, and parasites. However, bacterial infection is a common cause of sepsis and other inflammatory diseases. Originally,  people believed that gram-negative bacteria are the major causative organism for sepsis. However, recent studies have shown that gram-positive bacteria become the common cause sepsis.  Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Haemophilus influenzae b, Neisseria meningitides, staphylococcus, and streptococcus are important gram-negative and gram-positive bacteria for sepsis (). Upon infection, bacteria releases verity of factors, eventually this can reach systemic circulation and trigger severe inflammation leads to sepsis. A well-known toxin is lipopolysaccharide (LPS) of gram-negative bacteria. LPS is a major component of the outer leaflet of the outer membrane, being anchored to the membrane by the lipid A moiety and it demonstrates pro-inflammatory activity via Toll-like receptor 4(TLR4). Furthermore, Lipoteichoic acid (LTA), a diacylated glycolipid located on surface gram-positive bacteria. LTA is a crucial inflammatory molecule for gram-positive diseases equivalent of LPS of gram-negative bacteria.  LTA is recognized by Toll-like receptor 2 of an innate immune system. Although gram-positive sepsis causes up to 50 % mortality, very little study about the gram-positive bacterial component and One such component which has remained unexplored is Bacterial lipoprotein (Lpp).Lpp is a large group of surface protein in both gram-negative and gram-positive bacteria. In 1969, Braun and colleague first identified the lipoprotein in the membrane of Escherichia coli, Brun lipoprotein (). One-third of cumulative lipoprotein exist as a bound form with peptidoglycan layer while two-thirds are distributed as free form. Lpp is a fundamental component of bacterial physiology, essential for bacterial cell division, membrane transport process,  membrane stability, nutrient acquisition, conjugation and signal transduction (). Further, it is also necessary for bacterial pathologies like virulence, colonization, and evasion from immune responses ().Biosynthesis of LppLpp is a small-size protein contain C-terminal end (a lysine) covalently anchored to peptidoglycan layer of the cell wall and N-terminal cysteine modified with two or three fatty acids to form a functional diacylated or triacylated protein. More than 130 different lipoproteins have been characterized,  with a similar lipid part in both gram-negative and gram-positive bacteria.  Lpp is initially synthesized as a  pre-prolipoprotein, a precursor protein which carries additional 20 amino acid sequence at N- terminal end (a signal peptide). This signal peptide contains conserved residues at C -terminal end referred as lipobox. The canonical biosynthesis of Lpp was first established in E. coli by Braun and co-worker ().  After pro-lpp synthesized,  it is translocated on the cytoplasmic membrane via Sec-Tat machinery. Lpp biosynthesis consists of three major enzymatic reactions. the first reaction is carried out by phosphatidylglycerol:: prolipoproteindiacylglyceryl transferase (Lgt), catalyzes the transfer of a diacylglyceryl group from phosphatidylglycerol to the sulfhydryl group of the cysteine residue in the lipobox. The second step is catalyzed by signal peptidase II (Lsp) thatrecognize diacylglyceryl-prolipoprotein and remove the signal peptide at the amino-terminal end of diacylated cysteine. The third reaction is carried out by apolipoprotein N-acyltransferase (Lnt). this step is crucial for gram-negative bacteria, but not necessary for gram-negative bacteria. Lnt catalyzes the transfer of palmitic acid from Lpp in innate immune system activation via Toll-like receptor 2(TLR2)LPS of gram-negative bacteria is a potent activator of an innate immune system and this activation require an interaction of LPS and TLR4. In addition, lpp (Both gram-negative and gram-positive) is TLR2 mediated immune activation. the downstream of TLR2 requires an interaction with other TLRs.  Majority of gram-negative bacteria