cellwalltargeting

Cell wall targeting refers to strategies that disrupt, inhibit, or manipulate the cell wall of organisms, with important applications in medicine and research. It commonly centers on bacteria and fungi, where the cell wall provides essential structural integrity and enclosure of the cytoplasmic membrane. In bacteria, peptidoglycan is the main target; enzymes that synthesize and remodel the wall, such as penicillin-binding proteins (PBPs) and glycosyltransferases, are inhibited by various drug classes. Beta-lactam antibiotics (penicillins, cephalosporins, carbapenems) inhibit PBPs, preventing cross-linking of peptidoglycan. Glycopeptides (vancomycin, teicoplanin) bind the D-Ala-D-Ala termini of nascent wall precursors, blocking polymerization. Bacitracin interferes with the bactoprenol cycle required to transport wall precursors. Bacteriophages and lysins provide enzymatic means to degrade peptidoglycan from outside the cell. Resistance arises through beta-lactamases, altered PBPs, reduced permeability, and efflux.

In fungi, the cell wall contains chitin and beta-glucans; inhibiting their synthesis weakens the wall and causes lysis. Echinocandins inhibit beta-1,3-glucan synthase, while chitin synthase inhibitors such as nikkomycins and polyoxins target chitin formation. Some antifungal strategies also disrupt cell wall–membrane interactions or ergosterol synthesis, though these affect membranes rather than walls per se.

Challenges include the outer membrane barrier in Gram-negative bacteria, which reduces drug access, and the emergence of resistance. Cell wall targeting remains central to antimicrobial therapy and continues to be explored for novel agents, adjuvants, and industrial applications.