title: Antibiotic activity of iron-sequestering polymers.
abstract: 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.
authors: ∥Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors: Nashwa
authors: N
authors: El-Gendy
authors: Jian
authors: J
authors: Qian
authors: Kate
authors: K
authors: Eshelman
authors: Mario
authors: M
authors: Rivera
authors: §Department of Chemical and Petroleum Engineering, The University of Kansas, Learned Hall, 1530 West 15th, Lawrence, Kansas 66045, United States.
authors: Cory
authors: C
authors: Berkland
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use; D032701:Biomimetics; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry* / Q000494:pharmacology; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D062385:Hydroxybenzoates; D011073:Polyamines; D011108:Polymers; C063994:polyallylamine; C009135:2,3-dihydroxybenzoic acid; D007501:Iron