Indeed, the first WTA-active antibiotic has just been reported. Since then, however, new functions for WTAs in pathogenesis have been uncovered and it has been suggested that the biosynthetic enzymes that make these polymers are targets for novel antibacterial agents. Neuhaus and Baddiley comprehensively reviewed both LTAs and WTAs in 2003. Together, LTAs and WTAs create what has been aptly described as a “continuum of negative charge” that extends from the bacterial cell surface beyond the outermost layers of peptidoglycan. There are two types of TAs: the lipo-TAs (LTAs), which are anchored to the plasma membrane and extend from the cell surface into the peptidoglycan layer and the wall TAs (WTAs), which are covalently attached to peptidoglycan and extend through and beyond the cell wall ( Figure 1). These anionic polymers appear to perform some of the same functions as the outer membrane: they influence membrane permeability, mediate extracellular interactions, provide additional stability to the plasma membrane, and, along with peptidoglycan, act as scaffolds for extracytoplasmic enzymes required for cell-wall growth and degradation.Ī major class of these cell surface glycopolymers are the teichoic acids (TAs), which are phosphate-rich molecules found in a wide range of Gram-positive bacteria, pathogens and nonpathogens alike. Gram-positive peptidoglycan is heavily modified with carbohydrate-based anionic polymers that play an important role in membrane integrity. These thick layers of peptidoglycan stabilize the cell membrane and also provide many sites to which other molecules can be attached. The peptidoglycan layers are consequently very thick compared to those in Gram-negative organisms. Gram-positive organisms, in contrast, lack an outer membrane and a distinct periplasm ( Figure 1). LTA: lipoteichoic acid LPS: lipopolysaccharide WTA: wall teichoic acid. Membrane-embedded, membrane-anchored, and peptidoglycan-associated proteins are abundant in the cell membranes of both Gram-positive and Gram-negative organisms. Proteins are omitted from the depictions for clarity. Gram-negative organisms have a distinct periplasm Gram-positive organisms do not, but recent studies have suggested that they have a periplasmic-like compartment between the plasma membrane and the base of the peptidoglycan layers. Simplified depiction of Gram-positive and Gram-negative bacterial cell envelopes.
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