Antimicrobial and Innate Immune Tolerance Mechanisms in Biofilms

It is well documented that biofilms have inherent tolerance to killing and removal by biocides, antibiotics, and the innate immune system. While the matrix may impede antimicrobial transport, many antimicrobials reach the full depth of the biofilm but are inactive against the cells they reach. Clearance of biofilm infections can be hindered by delayed recruitment of immune responses. Nutrient depletion in the biofilm leads to slow or dormant growth but the transition to these dormant states can also trigger active metabolic adaptations and stress responses lending the cells in the biofilm to be unaffected. Transition to these tolerant states and changes in gene expression happen early in biofilm formation and even small biofilm clusters can challenge clearance. Biofilm growth as a multicellular community has a diversity of survival strategies and incomplete clearance leads to rapid recolonization. In this chapter, we will discuss how antimicrobial penetration, the distribution of physiological states, immune system recruitment, and bacterial responses to immune attack contribute to biofilm tolerance.