Genomic characterization of ribitol teichoic acid synthesis in Staphylococcus aureus: genes, genomic organization and gene duplication

Abstract

BackgroundStaphylococcus aureus or MRSA (Methicillin Resistant S. aureus), is an acquired pathogen and the primary cause of nosocomial infections worldwide. In S. aureus, teichoic acid is an essential component of the cell wall, and its biosynthesis is not yet well characterized. Studies in Bacillus subtilis have discovered two different pathways of teichoic acid biosynthesis, in two strains W23 and 168 respectively, namely teichoic acid ribitol (tar) and teichoic acid glycerol (tag). The genes involved in these two pathways are also characterized, tarA, tarB, tarD, tarI, tarJ, tarK, tarL for the tar pathway, and tagA, tagB, tagD, tagE, tagF for the tag pathway. With the genome sequences of several MRSA strains: Mu50, MW2, N315, MRSA252, COL as well as methicillin susceptible strain MSSA476 available, a comparative genomic analysis was performed to characterize teichoic acid biosynthesis in these S. aureus strains.ResultsWe identified all S. aureus tar and tag gene orthologs in the selected S. aureus strains which would contribute to teichoic acids sythesis.Based on our identification of genes orthologous to tarI, tarJ, tarL, which are specific to tar pathway in B. subtilis W23, we also concluded that tar is the major teichoic acid biogenesis pathway in S. aureus. Further analyses indicated that the S. aureus tar genes, different from the divergon organization in B. subtilis, are organized into several clusters in cis. Most interesting, compared with genes in B. subtilis tar pathway, the S. aureus tar specific genes (tarI,J,L) are duplicated in all six S. aureus genomes.ConclusionIn the S. aureus strains we analyzed, tar (teichoic acid ribitol) is the main teichoic acid biogenesis pathway. The tar genes are organized into several genomic groups in cis and the genes specific to tar (relative to tag): tarI, tarJ, tarL are duplicated. The genomic organization of the S. aureus tar pathway suggests their regulations are different when compared to B. subtilis tar or tag pathway, which are grouped in two operons in a divergon structure.

Comparison of Components and Synthesis Genes of Cell Wall Teichoic Acid amongLactobacillus plantarumStrains

“…On the basis of information on the tar genes found in B. subtilis W23, the genes involved in the synthesis of ribitol-type WTA in the genomes of S. aureus strains were reviewed recently. 29) For example, ispD and tagB in the genome of S. aureus NCTC 8325 (GenBank accession no. : CP000253, RefSeq accession no.…”

Wall Teichoic Acids of Gram-Positive Bacteria

“…In S. aureus , following formation of the lipid-diphospho-ManNAc-GlcNAc-GroP product by TarO, TarA and TarB, poly(RboP) synthesis continues with the TarF-mediated transfer of a (predominantly) single unit of glycerol-phosphate from CDP-glycerol, synthesized by TarD (9; 22; 24; 85; 135). As described above, the synthesis of poly(GroP) WTAs requires a GroP primase (TagB) as well as a GroP polymerase (TagF), and it was proposed that poly(RboP) WTA synthesis in S. aureus requires both a RboP primase and a RboP polymerase to make the main chain polymer (75; 105). Recent work has shown, however, that S. aureus contains a single enzyme, TarL, that primes the linkage unit and then attaches more than 40 ribitol-phosphates to complete the polymer (Figure 3) (24; 85; 97).…”

“…The CDP-ribitol substrate utilized by TarL is made by the combined action of TarI, a cytidylyl transferase, and TarJ, an alcohol dehydrogenase (96; 151). All S. aureus strains contain two sets of tarIJL genes (the second set is designated tarI’J’K ) (105). The significance of these duplications is still unclear (85; 97; 105; 120; 144).…”

“…All S. aureus strains contain two sets of tarIJL genes (the second set is designated tarI’J’K ) (105). The significance of these duplications is still unclear (85; 97; 105; 120; 144). …”

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

“…Decorating each ribitol at the 2- and 4-position carbon atoms are an α- or β-linked N-acetylglucosamine (α/β-O-GlcNAc), respectively, and an ester-linked D-alanine (D-alanyl ester). S. aureus WTA is synthesized by a group of eight enzymes found in the Tar (teichoic acid ribitol) operon, 24 with functionalization of the ribitol groups performed by the enzymes TarM and TarS (α-GlcNAc and β-GlcNAc) 25 and enzymes from the Dlt operon (D-alanyl ester) 26 (Figure 1). Importantly, S. aureus WTA has vital roles in colonization and virulence 27 with terminal modifications such as D-alanylation and β-O-GlcNAcylation required for resistance to anti-microbial peptides 28 and methicillin, 29 suggesting that the presence of WTA is essential for productive infection.…”