Polymicrobial biofilms are frequently associated with chronic infections and are highly tolerant to antibiotic treatment. Given that β-lactam antibiotics are the most prescribed antibiotics worldwide, we investigated β-lactam resistance in dual-species biofilms formed by Pseudomonas aeruginosa PAO1 and methicillin-sensitive Staphylococcus aureus (MSSA). Compared to monocultures, MSSA exhibited reduced susceptibility to cephalexin, ampicillin, and cefazolin, while P. aeruginosa showed reduced susceptibility to cefazolin and nafcillin within dual-species biofilms. Using a set of P. aeruginosa mutants, we demonstrate that the PAO1 AmpC β-lactamase, the exopolysaccharides Psl and Pel, and the quorum sensing regulators LasR and RhlR each play significant roles in protecting MSSA from β-lactam treatment. Interestingly, co-cultures of MSSA with the ΔpslA pelF mutant strain increased the survival of ΔpslA pelF under β-lactam exposure. Overall, these findings advance our understanding of how interdependent bacterial interactions compensate for the loss of matrix components and thereby contribute to antimicrobial tolerance in polymicrobial biofilms.
Nizer et al. (Wed,) studied this question.