Question

Structural features and functional consequence of gram-positive and gram-negative bacterial cell wall composition related to antibiotic susceptibility

Answer 1

The cell wall in bacteria is an important structure to determine the shape of bacteria. It provides structural support and keeps the bacteria intact even in constantly changing environmental conditions. The cell wall of most bacteria gains the strength and stability by presence of peptidoglycan (PG).

The PG is composed of repeating units of long glycan chains or sugar units cross linked by short peptide fragments. The amount and composition of peptidoglycan may vary in different bacteria. The antibiotic drugs such as penicillins and cephalosporines are used to treat infections effectively because these drugs target the peptide cross links in peptidoglycan. The antibiotics may disrupt the integrity of cell wall and the cells may undergo lysis.

The gram positive cell wall is thick and is composed of peptidoglycan of 20 to 80nm of thickness. It also contains acidic polysaccharides and teichoic acid attached to the peptidoglyhcan and lipoteichoic acid. The teichoic present in the cell wall is a polymer of ribitol or glycerol and phosphate embedded in the sheath of peptidoglycan. The lipoteichoic acid is also a similar structure but is attached to lipids in the plasma membrane.

These molecules have a role in maintenance of cell wall, cell enlargement during cell division and binding of pathogens to host tissues. The cell wall of gram positive bacteria is loosely adhered to the cell membrane but the junction of both the layers is separated by a compartment called periplasmic space. This is similar to large space in gram negative bacteria but the function is different .

Periplasmic space contains enzymes released by cell membranes and the space is the site of synthesis of peptidoglycan. Gram negative cell wall has complex morphology as it is composed of an outer membrane (OM). The peptidoglycan is a thin layer and the outer membrane is similar to cell membrane in its construction but contains special types of lipopolysaccharides (LPS) and lipoproteins.

The lipopolysaccharides contain lipid molecules bound to polysaccharides. The lipids form as a matrix of top layer of OM and the polysaccharides extend from the lipid surface. The lipid portion acts as a toxic when released during infection and is known as endotoxin. The polysaccharide produce somatic (O) antigen.

The polysaccharides may also act as receptors that may interfere with host defenses. The gram positive cells exposed to antibiotic penicillin will lose the cell wall and form a protoplast. Protoplast is a fragile cell and is susceptible to lysis. Though the peptidoglycan is thick in gram positive bacteria compared to gram negative bacteria, the penicillin targets peptide cross linking of peptidoglycan and gram positive bacteria are highly susceptible to penicillins. But, these bacteria also gained resistance to penicillin as they have evolved with penicillin binding proteins (PBPs).

Due to less amount of PG, the gram negative bacteria are least susceptible to penicillin. Several other antibiotics have been developed that can individually target the other components of cell wall of gram psotive and gram negativebacteria but the evolution of bacteria enable them to become resistant to most of the antibiotics.