Which factor makes bacteria most resistant to antibiotics?

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric matrix. Within this matrix, bacteria exhibit dramatically increased resistance to antibiotics through multiple mechanisms: the matrix physically restricts antibiotic penetration, slow-growing 'persister' cells are tolerant to killing, horizontal gene transfer of resistance genes is facilitated, and quorum-sensing coordinates gene expression for collective defense. Biofilm-mediated resistance can be 10- to 1000-fold greater than planktonic (free-floating) bacteria. Dental plaque is a classic example of a pathogenic biofilm.