Lipopolysaccharide-affinity copolymer senses the rapid motility of swarmer bacteria to trigger antimicrobial drug release

Abstract

An intelligent drug release system that is triggered into action upon sensing the motion of swarmer P. mirabilis is introduced. The rational design of the drug release system focuses on a pNIPAAm-co-pAEMA copolymer that prevents drug leakage in a tobramycin-loaded mesoporous silica particle by covering its surface via electrostatic attraction. The copolymer chains are also conjugated to peptide ligands YVLWKRKRKFCFI-NH2 that display affinity to Gram-negative bacteria. When swarmer P. mirabilis cells approach and come in contact with the particle, the copolymer-YVLWKRKRKFCFI-NH2 binds to the lipopolysaccharides on the outer membrane of motile P. mirabilis and are stripped off the particle surface when the cells move away; hence releasing tobramycin into the swarmer colony and inhibiting its expansion. The release mechanism is termed Motion-Induced Mechanical Stripping (MIMS). For swarmer B. subtilis, the removal of copolymers from particle surfaces via MIMS is not apparent due to poor adherence between bacteria and copolymer-YVLWKRKRKFCFI-NH2 system.