Microbial cell wall and membrane structures

Microbial cell wall and membrane structures are essential components that provide structural integrity, protection against osmotic pressure, and a selective barrier for nutrient transport in bacteria and fungi [1]. In bacteria, the cell wall is primarily composed of peptidoglycan, a complex polymer of sugars and amino acids, while the cytoplasmic membrane consists of a phospholipid bilayer [1, 2]. Fungal cell walls contain chitin and glucans, and their membranes are characterized by the presence of ergosterol [3]. These structures are critical therapeutic targets because they are often unique to microbes, allowing for selective toxicity with minimal impact on host cells [2, 4]. Drugs targeting these structures, such as beta-lactams, glycopeptides, and polymyxins, work by inhibiting synthesis or disrupting structural integrity, leading to cell lysis and death [4, 5]. Beta-lactams specifically inhibit the transpeptidation step of peptidoglycan synthesis, while glycopeptides like vancomycin bind to the D-Ala-D-Ala terminus of the cell wall precursor [2, 4]. Membrane-active agents like daptomycin and polymyxins disrupt the integrity of the cytoplasmic or outer membranes, causing leakage of cellular contents [4, 5]. Antifungal agents like polyenes bind to ergosterol, while azoles inhibit its synthesis, both leading to compromised membrane function [3]. The emergence of antimicrobial resistance, such as through the production of beta-lactamases or modification of target sites, remains a significant clinical challenge [5]. Despite these challenges, targeting the microbial envelope remains a cornerstone of infectious disease treatment due to the fundamental necessity of these structures for microbial survival [4]. References: [1] Silhavy, T. J., et al. (2010) Cold Spring Harb Perspect Biol. [2] Bugg, T. D., et al. (2011) Nat Rev Microbiol. [3] Gow, N. A. R., et al. (2017) Microbiol Spectr. [4] Kohanski, M. A., et al. (2010) Nat Rev Microbiol. [5] Lewis, K. (2013) Nat Rev Drug Discov.

Other names

Bacterial cell wallFungal cell wallCytoplasmic membranePeptidoglycan layerOuter membraneBacterial cell envelope

Inhibition of peptidoglycan cross-linking, inhibition of cell wall precursor synthesis, disruption of membrane potential, pore formation in the cytoplasmic membrane, and inhibition of ergosterol synthesis or binding.