Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms

• Protection against oxidative stress provides microbial biofilms with tolerance to cidal drugs.
• In bacteria, the antibiotic-induced expression of efflux systems is linked to biofilm resistance.
• The biofilm matrix and cell envelope-associated polysaccharides contribute to tolerance.
• There is evidence that suggests these mechanisms are not independent.

The formation of microbial biofilms is an important reason for failure of antimicrobial therapy. However, the molecular mechanisms underlying the survival of biofilm cells are still not completely understood. In this review we discuss three mechanisms that play an important role in biofilm survival: (i) biofilm-specific protection against oxidative stress; (ii) biofilm-specific expression of efflux pumps; and (iii) protection provided by matrix polysaccharides. We demonstrate that these mechanisms are found both in bacterial and fungal biofilms and are often surprisingly similar between distantly related organisms. In addition, we give an overview of the data that suggests that these mechanisms may not be independent.