Recent Advances in Peptidoglycan Synthesis and Regulation in Bacteria

Abstract

Bacteria must synthesize their cell wall and membrane during their cell cycle, with peptidoglycan being the primary component of the cell wall in most bacteria. Peptidoglycan is a three-dimensional polymer that enables bacteria to resist cytoplasmic osmotic pressure, maintain their cell shape and protect themselves from environmental threats. Numerous antibiotics that are currently used target enzymes involved in the synthesis of the cell wall, particularly peptidoglycan synthases. In this review, we highlight recent progress in our understanding of peptidoglycan synthesis, remodeling, repair, and regulation in two model bacteria: the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. By summarizing the latest findings in this field, we hope to provide a comprehensive overview of peptidoglycan biology, which is critical for our understanding of bacterial adaptation and antibiotic resistance.

The footprint of gut microbiota in gallbladder cancer: a mechanistic review

“…(NPHS) also possessed genes encoding the enzyme N-acetyltransferase, which exhibited similar LPS biosynthesis functions, indicating that the bacterial metabolite LPS oncogenic pathway is common in GBC carcinogenesis ( Griffiths et al., 2021 ). Second, peptidoglycan biosynthesis is another product of bacterial metabolism of carbohydrates ( Galinier et al., 2023 ). H. hepaticus may be a human pathogen that causes GBC, and the pathogenesis is highly likely to be the proinflammatory response that is mediated by peptidoglycans and LPS on the cell wall ( Falsafi and Mahboubi, 2013 ).…”

Real-Time Biosynthetic Reaction Monitoring Informs the Mechanism of Action of Antibiotics

“…Lipid I is subsequently glycosylated into lipid II by MurG, and then transported across the membrane by flippases such as MurJ and Amj. − The carrier lipid is finally released as undecaprenyl diphosphate (C 55 -PP) after the glycopeptide moieties are incorporated into the nascent peptidoglycan polymer by the penicillin-binding proteins and other machineries (Figure A). − C 55 -PP is also synthesized de novo but must first be dephosphorylated before it can be used for translocating cell wall precursors . Carrier lipid molecules are dephosphorylated by phosphatases of the UppP or PAP2 families, , and are transported back across the plasma membrane by DedA and DUF368 family proteins ,, before re-entering the lipid II cycle . Most of the antibiotics that interfere with this peptidoglycan biosynthesis pathway appear to specifically act by sequestering the key membrane-bound intermediates, namely, C 55 -P, C 55 -PP, lipid-I, and lipid-II, rather than by targeting the enzymes themselves.…”

“…26,27 These membrane enzymes are involved in carrier lipid metabolisms which is important for the biosynthesis of peptidoglycan and other cell envelope polymers. 28 Synthesis of peptidoglycan, a highly conserved component of the bacterial cell wall and the target of many successful antibiotics, 29 begins in the cytosol with the synthesis of disaccharide pentapeptide precursors 30 which are then attached to C 55 -P by MraY to form lipid I. 31 subsequently glycosylated into lipid II by MurG, 32 and then transported across the membrane by flippases such as MurJ and Amj.…”

“…36−38 C 55 -PP is also synthesized de novo but must first be dephosphorylated before it can be used for translocating cell wall precursors. 39 Carrier lipid molecules are dephosphorylated by phosphatases of the UppP or PAP2 families, 40,41 and are transported back across the plasma membrane by DedA and DUF368 family proteins 28,42,43 before re-entering the lipid II cycle. 44 Most of the antibiotics that interfere with this peptidoglycan biosynthesis pathway appear to specifically act by sequestering the key membrane-bound intermediates, namely, C 55 -P, C 55 -PP, lipid-I, and lipid-II, rather than by targeting the enzymes themselves.…”

“…We aimed to develop a combination of real-time enzyme activity monitoring and in situ inhibition to yield a mechanistic insight into the MoA of antibiotics. To develop our approach, we selected two Escherichia coli membrane phosphatases UppP and PgpB as model membrane enzymes, having different substrate specificities. , These membrane enzymes are involved in carrier lipid metabolisms which is important for the biosynthesis of peptidoglycan and other cell envelope polymers …”