Gram-negative bacterial cell envelope and biofilm structures

The Gram-negative bacterial cell envelope and biofilm structures constitute a sophisticated defense system that protects bacteria from both the host immune response and antimicrobial therapy (Silhavy et al., 2010, Cold Spring Harb Perspect Biol). The cell envelope is characterized by a unique outer membrane containing lipopolysaccharides (LPS), which serves as a formidable permeability barrier against many antibiotics. Biofilms are multicellular communities of bacteria encased within a self-produced matrix of extracellular polymeric substances (EPS), including polysaccharides, proteins, and extracellular DNA (Flemming & Wingender, 2010, Nat Rev Microbiol). These structures are primary drivers of chronic and healthcare-associated infections, as they facilitate persistent colonization and provide a protected environment where bacteria can survive high concentrations of antibiotics. Therapeutic strategies often focus on disrupting the physical integrity of the outer membrane or enzymatically degrading the biofilm matrix to restore the efficacy of traditional antimicrobial agents (Breijyeh et al., 2020, Molecules).

Other names

Gram-negative cell wallOuter membraneBacterial extracellular matrixBiofilm matrixExtracellular polymeric substances (EPS)

Drugs targeting these structures work by disrupting the outer membrane integrity (e.g., polymyxins binding to LPS), inhibiting the synthesis of the peptidoglycan layer (e.g., beta-lactams), or degrading the extracellular polymeric matrix of biofilms to enhance antibiotic penetration (Breijyeh et al., 2020, Molecules).