Peptidoglycan: Structures and Recognition

Abstract

Bacteria are identified in many different shapes, like cocci and rods, and internal volumes from 10-2 to 106 μm. For this different shapes and sizes, it sounds obvious that there is a regulated process that allows the cell wall of bacteria to grow and divide. The major structural component of the cell wall of bacteria is peptidoglycan (PGN). Peptidoglycan comes in two forms in bacteria. Gram-positive bacteria contain a thick layer of PGN outside the cell membrane and gram-negative bacteria have a thin layer f PGN between their inner and outer cell membrane. PGN is build of repeartoins of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues. These repeations of glycan strands that are connected to each other by peptide stems that are attached to the MurNAc residue. Bacteria live under large pressure of antibiotics and immune systems that are specialized in the recognition and killing of bacteria. Specific receptors have evolved in these immune systems that recognize specific conserved structures in bacteria. Therefore bacteria have also been evolved, which yielded structural alterations, that provide bacteria with immune evasion strategies. However, the human innate immune system is still able to recognize different structures in the bacterial cell wall. In this overview I will highlight in what level the human immune system is able to recognize parts of peptidoglycan. Pattern recognition receptors are identified as proteins that recognize parts of the peptidoglycan. Peptidoglycan recognition proteins are the first receptors described in this article. The human innate immune system has 4 different types of PGRP. Next to these PGN specific receptors, we also have toll-like receptors. these TLRs are able to recognize specific microbial structures. They act on outer cell membranes and inner cell membranes and their signaling cascade after activation seems to be interconnected and very complex. Together with the TLR, Nod-like receptors (NLR) are the most well known pattern recognition receptors. Of the NLR family, Nod1 and Nod2, are known as being able to recognize DAP and MDP structures from the PGN layers in bacteria. There are results that also a relation between signaling pathways activated by Nod and TLR proteins. There are also controversial results that makes it very interesting to do further research into this subject, for example about the actual ligand that activates TLR2.