Cell wall assembly in Bacillus subtilis: how spirals and spaces challenge paradigms

Abstract

SummaryAlthough the bacterial cell wall has been the subject of decades of investigation, recent studies continue to generate novel and controversial models of its synthesis and assembly. Here we compare and contrast the transcompartmental biosyntheses of peptidoglycan and teichoic acid in Bacillus subtilis . In addition, the current paradigms of B. subtilis wall assembly and structure are distinguished from emerging models of murein insertion and organization. We discuss evidence for the directed, cytoskeleton-dependent insertion of nascent peptidoglycan and the existence of a periplasmic compartment. Furthermore, we summarize the challenges these findings represent to the existing paradigm of murein insertion. Finally, motivated by these new developments, we discuss outstanding issues that remain to be addressed and suggest research directions that may contribute to a better understanding of cell wall assembly in B. subtilis .

Bioinformatic insights into the biosynthesis of the Group B carbohydrate in Streptococcus agalactiae

“…Also consistent with this definition of GBC as the teichoic-acid-like polymer of S. agalactiae is the observation that the stem oligosaccharide IV (Figs 1 and 2) is covalently attached to N-acetylmuramic acid (NAM) residues of the cell-wall peptidoglycan (Deng et al, 2000). Finally, it should be noted that, contrary to a previous preliminary report of a glycerophosphate teichoic acid (Goldschmidt & Panos, 1984), genomic analysis suggests S. agalactiae is unable to synthesize poly(glycerophosphate) teichoic acids as obvious orthologues of the crucial enzymes for glycerol 3-phosphate polymerization (TagB, TagD and TagF; Bhavsar & Brown, 2006) are not encoded in the S. agalactiae genome (our observations). This latter observation is of additional importance as it provides further evidence that lipoteichoic acid is the predominant poly(glycerophosphate) cell envelope polymer in S. agalactiae (Doran et al, 2005;Henneke & Berner, 2006).…”

“…These polymers or their repeat units are assembled on a polyisoprenol-phosphate carrier molecule (typically undecaprenylphosphate) and ultimately flipped to the extracytoplasmic face of the plasma membrane before their assembly and/or final localization. In Gram-positive bacteria, this model also holds true for the biosynthesis of poly(glycerophosphate) teichoic acids (Bhavsar & Brown, 2006;Damjanovic et al, 2007) and various capsular polysaccharides (Bentley et al, 2006). This strategy may facilitate co-ordination between peptidoglycan assembly and the attachment of polymers that are covalently linked to the glycan repeat units, which includes the capsular polysaccharide and GBC in S. agalactiae (Deng et al, 2000).…”

“…Many cell-envelope polymers (most notably peptidoglycan, lipopolysaccharide and capsular polysaccharides) are synthesized, at least in part, at the cytoplasmic face of the plasma membrane as the requisite nucleotide-activated precursors are intracellular Bhavsar & Brown, 2006;Whitfield, 2006). These polymers or their repeat units are assembled on a polyisoprenol-phosphate carrier molecule (typically undecaprenylphosphate) and ultimately flipped to the extracytoplasmic face of the plasma membrane before their assembly and/or final localization.…”

Cell envelope gene expression in phosphate-limited Bacillus subtilis cells

“…Importantly peptidoglycan synthesis continues at a significant rate during this change in anionic polymer composition (Bisicchia et al, 2007). Teichoic acid and peptidoglycan metabolism in B. subtilis are linked in two crucial ways: (i) teichoic acid is covalently bound to peptidoglycan and (ii) the subunits of peptidoglycan (Lipid II) and teichoic acid (undecaprenylpyrophosphoryl-GlcNAc-ManNAc-polyglycerol phosphate) synthesis are both assembled intracellularly using the same pool of undecaprenol phosphate (Bhavsar & Brown, 2006;Bouhss et al, 2008;Weidenmaier & Peschel, 2008;Swoboda et al, 2010). Thus coordinate regulation of peptidoglycan and anionic polymer synthesis must occur during exponential growth and under phosphate-limiting conditions.…”

Inhibition of the First Step in Synthesis of the Mycobacterial Cell Wall Core, Catalyzed by the GlcNAc-1-phosphate Transferase WecA, by the Novel Caprazamycin Derivative CPZEN-45

“…With a combination of approaches such as evaluation of macromolecular biosynthesis, property of spontaneous drugresistant strains or genetically modified strains, and enzymatic activity, the primary target of CPZEN-45 in B. subtilis was identified as TagO involved in the biosynthesis of teichoic acid, which is a major component of the cell wall of Gram-positive bacteria (12,13). Furthermore, inhibition of WecA of M. tuberculosis, which is the ortholog of TagO of B. subtilis, by CPZEN-45 was also established.…”