Inhibitors of Bacterial Cell Wall Synthesis
A prime target for antimicrobial chemotherapy is the cell wall, since practically all bacteria (with the exception of mycoplasmas) have it, whereas mammalian cells lack this feature. Several groups of antibiotics, notably b-lactam agents (penicillins, cephalosporins, monobactams, carbapenems) and glycopeptides (vancomycin and teicoplanin) act on this specific target. A few less important antibiotics also act at this level and some compounds used in the treatment of tuberculosis and leprosy act on the specialized mycobacterial cell wall.
In general bacterial cell walls conform to two basic patterns, which can be distinguished by that most familiar of all microbiological techniques, the Gram stain. Gram-positive (staphylococci, streptococci, etc.) and Gram-negative (escherichia, pseudomonas, klebsiella, etc.) bacteria respond differently to cell wall active agents and it is helpful to understand the basis for this difference.
Cell wall construction
Fig. 1 Simplified scheme of bacterial
cell wall synthesis and action sites of cell wall-active antibiotics
In Gram-positive bacteria the cell wall
structure is thick (about 30 nm), tightly cross-linked, and embedded with
polysugarphosphates (teichoic acids), some of which have a lipophilic tail
buried in the cell membrane (lipoteichoic acids). Gram-negative bacteria, in
contrast, have a relatively thin (2-3 nm), loosely cross-linked peptidoglycan
layer and do not have teichoic acid, but have other components like lipid A.
External to the Gram-negative peptidoglycan is a membrane-like structure,
composed mainly of lipopolysaccharide and lipoprotein, which prevents large
molecules such as glycopeptides from entering the cell. Small hydrophilic
molecules enter Gram-negative bacilli through aqueous channels called porins.
Differential activity among some groups of antibiotics, notably the penicillins
and cephalosporins, is influenced by their ability to pass through these porin
channels which largely depend on the size and ionic charge of substituents
carried by the antibacterial agents.
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