LytR-CpsA-Psr Glycopolymer Transferases: Essential Bricks in Gram-Positive Bacterial Cell Wall Assembly

Abstract

The cell walls of Gram-positive bacteria contain a variety of glycopolymers (CWGPs), a significant proportion of which are covalently linked to the peptidoglycan (PGN) scaffolding structure. Prominent CWGPs include wall teichoic acids of Staphylococcus aureus, streptococcal capsules, mycobacterial arabinogalactan, and rhamnose-containing polysaccharides of lactic acid bacteria. CWGPs serve important roles in bacterial cellular functions, morphology, and virulence. Despite evident differences in composition, structure and underlaying biosynthesis pathways, the final ligation step of CWGPs to the PGN backbone involves a conserved class of enzymes—the LytR-CpsA-Psr (LCP) transferases. Typically, the enzymes are present in multiple copies displaying partly functional redundancy and/or preference for a distinct CWGP type. LCP enzymes require a lipid-phosphate-linked glycan precursor substrate and catalyse, with a certain degree of promiscuity, CWGP transfer to PGN of different maturation stages, according to in vitro evidence. The prototype attachment mode is that to the C6-OH of N-acetylmuramic acid residues via installation of a phosphodiester bond. In some cases, attachment proceeds to N-acetylglucosamine residues of PGN—in the case of the Streptococcus agalactiae capsule, even without involvement of a phosphate bond. A novel aspect of LCP enzymes concerns a predicted role in protein glycosylation in Actinomyces oris. Available crystal structures provide further insight into the catalytic mechanism of this biologically important class of enzymes, which are gaining attention as new targets for antibacterial drug discovery to counteract the emergence of multidrug resistant bacteria.

Proteomic Analysis Reveals Enzymes for β-D-Glucan Formation and Degradation in Levilactobacillus brevis TMW 1.2112

“…In conclusion, β-glucan is not used as a storage compound by L. brevis TMW 1.2112. The CPS therefore might have mostly a protective function according to the strain’s origin from beer with present ethanol, low pH, or antimicrobial hop compounds [ 34 , 95 ].…”

Structural variations and roles of rhamnose-rich cell wall polysaccharides in Gram-positive bacteria

“…RgpC and RgpD encode a permease and an ATP-binding protein, respectively, and together constitute the ABC transporter responsible for exporting the elongated chain outside the cytoplasmic membrane. In the final step, the rhamnan chain is anchored covalently onto peptidoglycan, most probably by a transferase in the LytR-CpsA-Psr (LCP) family ( 53 ), which catalyzes the transfer of the phospho-chain onto MurNAc residues of the peptidoglycan chains ( 14 ) ( Fig. 3 ), as described below in more detail.…”

“…LCP proteins were first identified as the enzymes involved in the ligation of WTA onto peptidoglycan ( 68 ). They are phosphotransferases that catalyze the transfer of the reducing end of the glycopolymer chain to peptidoglycan from a lipid carrier–bound intermediate (C 55 -PP-glycopolymer); this is accomplished via the formation of a phosphodiester bond with the C6 hydroxyl group of MurNAc (or GlcNAc) residues of the glycan chains of peptidoglycan ( 53 , 69 , 70 ). LCP proteins, initially characterized in B. subtilis , are widely distributed in Gram-positive bacteria.…”

Post-translational Modifications in Oral Bacteria and Their Functional Impact

“…LCP transferase can glycosylate GspA that regulates sortase enzyme (SrtA) activity, vital for bacterial survival, and can arrest A. oris . In S. agalactiae , CpsA is covalently attached to GlcNac of the peptidoglycan (PGN) backbone and is involved in cell wall maintenance and capsular polysaccharide (CPSCPS) synthesis ( Stefanovic et al, 2021 ). Although known for many years, the study of N -glycosylation in oral bacteria is limited, necessitating further exploration.…”