Biofilms: the Achilles’ Heel of Antimicrobial Resistance

Microbial biofilms are communities of sessile cells with a three-dimensional (3D) extracellular polymeric substance (EPS). The EPS consists of exopolysaccharides, nucleic acids (eDNA and eRNA), proteins, lipids, and other biomolecules, that they produce and are irreversibly attached to living or non-living surfaces. This is the most frequent growth mode of microorganisms in nature. The biofilm formation consists of several steps, starting with attachment to a surface and the formation of microcolonies. Subsequently, in the maturation step, three-dimensional structures are formed and end the life cycle of biofilms with the dispersal or detachment of the cells. This type of growth has been reported to be more resistant to antimicrobial treatment and immune response than its planktonic (free-living) counterparts. Several intrinsic resistance factors including the interaction between antimicrobial and biofilm matrix components, reduced growth rates, persister cells presence, increased production of oxidative stress, and antagonist and degradation mechanisms may be active in some parts of the biofilms have been described. Extrinsic factors such as increased horizontal genes transmission conferring antimicrobial resistance have been described contributing to the biofilm antimicrobial resistance. Due to the heterogeneous nature of biofilms, it is likely that multiple mechanisms of biofilm antimicrobial resistance are useful in order to explain biofilm survival in a number of cases, being the result of an intricate mixture of intrinsic and extrinsic factors. The understanding of the nature of biofilm development and drug tolerance are great challenges for the use of conventional antimicrobial agents and indicate the need for multi-targeted or combinatorial therapies.