Antibiotic activity of iron-sequestering polymers

Increasing antibiotic resistance has compelled the development of novel antibiotics and adjuvant therapies that enhance the efficacy of existing antibiotics. Iron plays a critical role in bacterial infections, yet the use of iron chelators as adjuvant therapy with antibiotics has yielded highly variable outcomes. Multivalent polymeric materials offer an alternative approach to bind and sequester iron via high avidity interactions. Here, a biomimetic iron-sequestering polymer (PAI-DHBA) was synthesized by modifying side chains of cross-linked polyallylamine (cPAI) with 2,3-dihydroxybenzoic acid (DHBA). PAI-DHBA polymer gels with various DHBA contents showed high iron affinity indices and high selectivity for iron. The polymers showed mild antibiotic properties when used to treat established bacterial cultures. Pretreating culture media with PAI-DHBA polymer, however, removed all detectable iron from media and effectively inhibited the growth of Pseudomonas aeruginosa. In addition, bacterial growth was more susceptible to antibiotics combined with PAI-DHBA. Multivalent polymers that bind and sequester iron, such as PAI-DHBA, offer a promising early intervention or adjuvant to antibiotics.