Advanced Microbial Physiology

Lecture 2Cell Wall Biosynthesis

Bacterial Cell Walls

Peptidoglycans of Cell Walls

Peptidoglycan or murein is an enormous polymer composed of identical subunits

It consists of long chains of repeating units of 2 sugar derivatives N-acetylglucosamine (NAG), and N-acetylmuramic acid (NAM)

Sugar chains are cross-linked between tetrapetide chains originated from NAM

Most Gram negative bacterialack the peptide interbridge made up by glycines

Many Gram positive bacteria have the glycine interbridge

Synthesis of Peptidoglycan

Murein biosynthesis involves a number of cytoplasmic, membrane and periplasmic steps

NAG is first coupled with UDP A portion of UDP-NAG is converted into UDP-

NAM, and the peptide chain is developed by sequential addition of amino acid

NAM-pentapeptide binds to undecaprenyl-phosphate and merged with NAG of UDP-NAG

Disaccharide-pentapeptide is adding to the growing chain of peptidoglycan chains

Gene Cluster for Cell Wall Syn

MurA UDP-N-acetylglucosamine 1-carboxyvinyltransferase  MurB UDP-N-acetylenolpyruvoylglucosamine reductase  MurC UDP-N-acetylmuramate--L-alanine ligase  MurD UDP-N-acetylmuramoylalanine--D-glutamate ligase  MurE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase MurF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase  MurG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-

undecaprenol N-acetylglucosamine transferaseMurI Glutamate racemase  MraY Phospho-N-acetylmuramoyl-pentapeptide-transferase  

Penicillin-binding proteins

Bacterial cells contain a variety of penicillin-binding proteins (PBPs)

PBPs belong to the family of acyl serine transferases, which includes high-molecular-weight (HMW) PBPs, low-molecular-weight (LMW) PBPs, and b-lactamases.

HMW PBPs are enzymes that are composed of two modules located on the outer surface of the cytoplasm membrane and anchored to the cytoplasmic membrane by an N-terminal, non-cleavable signal peptide.

Penicillin-binding proteins

The C-terminal module is the penicillin-binding domain, which catalyzes the cross-linking of the peptidoglycan peptides

HMW PBPs can be divided into 2 classes: Class A, possessing both transglycosylase and

transpeptidase activity Class B, with only transpeptidase activity

Incorporation of New Cell Wall

Rod-shaped bacteria have two modes of cell wall synthesis: New PG is inserted along a helical path, or New PG is inserted in a closing ring, leading to

septum formation Rugby-ball-shaped Streptococcus elongate by

inserting new cell wall at the equatorial rings, then forms division septum in the middle of the cell.

Round cells do not seem to have an elongation mode of cell wall synthesis.

Proposed mode of insertion of new PG