Mucus and mucin biopolymer environments reduce the efficacy of polymyxin and fluoroquinolone antibiotics

Mucus, a biopolymer hydrogel that covers all wet epithelia, is one of the primary arenas for microbes in the body, including the microbiome and pathogenic microbes that can cause serious infections. Mucus has the potential to bind small molecules and influence bacterial physiology, two factors that might affect the efficacy of antibiotics. Despite this, the impact of mucus on antibiotic efficacy has not been thoroughly characterized. We investigated the efficacy of polymyxin and fluoroquinolone antibiotics against the opportunistic pathogen Pseudomonas aeruginosa in native mucus and purified mucin biopolymer environments. We found that mucus reduces the efficacy of polymyxin and fluoroquinolone antibiotics against P. aeruginosa. MUC5AC, MUC2, and MUC5B mucin biopolymers, the gel-forming components of mucus, are primary contributors to this reduced efficacy. Our findings highlight that inclusion of the biomaterial environmental context is an important consideration when evaluating antimicrobial efficacy in vitro.