Functional conservation of the lipid II biosynthesis pathway in the cell wall-less bacteria Chlamydia and Wolbachia: why is lipid II needed?

Abstract

Cell division and cell wall biosynthesis in prokaryotes are driven by partially overlapping multiprotein machineries whose activities are tightly controlled and co-ordinated. So far, a number of protein components have been identified and acknowledged as essential for both fundamental cellular processes. Genes for enzymes of both machineries have been found in the genomes of the cell wall-less genera Chlamydia and Wolbachia, raising questions as to the functionality of the lipid II biosynthesis pathway and reasons for its conservation. We provide evidence on three levels that the lipid II biosynthesis pathway is indeed functional and essential in both genera: (i) fosfomycin, an inhibitor of MurA, catalysing the initial reaction in lipid II biosynthesis, has a detrimental effect on growth of Wolbachia cells; (ii) isolated cytoplasmic membranes from Wolbachia synthesize lipid II ex vivo; and (iii) recombinant MraY and MurG from Chlamydia and Wolbachia exhibit in vitro activity, synthesizing lipid I and lipid II respectively. We discuss the hypothesis that the necessity for maintaining lipid II biosynthesis in cell wall-lacking bacteria reflects an essential role of the precursor in prokaryotic cell division. Our results also indicate that the lipid II pathway may be exploited as an antibacterial target for chlamydial and filarial infections.

• Authors: Beate Henrichfreise, Andrea Schiefer, Tanja Schneider, Edith Nzukou, Christina Poellinger, Theo-Julian Hoffmann, Kelly L Johnston, Katja Moelleken, Imke Wiedemann, Kenneth Pfarr, Achim Hoerauf, Hans Georg Sahl
• Journal: Molecular microbiology (Mol Microbiol) Vol. 73 Issue 5 Pg. 913-23 (Sep 2009) ISSN: 1365-2958 [Electronic] England
• PMID: 19656295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Outer Membrane Proteins
• Bacterial Proteins
• Enzyme Inhibitors
• Monosaccharides
• Oligopeptides
• Uridine Diphosphate N-Acetylmuramic Acid
• lipid I
• muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
• Fosfomycin
• Transferases
• N-Acetylglucosaminyltransferases
• UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase
• Alkyl and Aryl Transferases
• UDP-N-acetylglucosamine 1-carboxyvinyltransferase
• Transferases (Other Substituted Phosphate Groups)
• mraY protein, Bacteria

Topics

• Alkyl and Aryl Transferases (antagonists & inhibitors)
• Bacterial Outer Membrane Proteins (isolation & purification, metabolism)
• Bacterial Proteins (isolation & purification, metabolism)
• Biosynthetic Pathways (genetics)
• Cell Membrane (metabolism)
• Chlamydia (drug effects, genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• Fosfomycin (pharmacology)
• Genes, Bacterial
• Genes, Essential
• Models, Biological
• Monosaccharides (metabolism)
• N-Acetylglucosaminyltransferases (isolation & purification, metabolism)
• Oligopeptides (metabolism)
• Transferases (isolation & purification, metabolism)
• Transferases (Other Substituted Phosphate Groups)
• Uridine Diphosphate N-Acetylmuramic Acid (analogs & derivatives, biosynthesis)
• Wolbachia (drug effects, genetics, metabolism)