Antimicrobial peptide HPA3NT3-A2 effectively inhibits biofilm formation in mice infected with drug-resistant bacteriaElectronic supplementary information (ESI) available. See DOI: 10.1039/c9bm01051c

Bacterial biofilms formed through secretion of extracellular polymeric substances (EPS) have been implicated in many serious infections and can increase antibiotic resistance by a factor of more than 1000. Here, we examined the abilities of the antimicrobial peptide HPA3NT3-A2 to inhibit and reduce biofilm formation, eliminate EPS, and suppress inflammation in mice infected with clinical isolates of drug-resistant Pseudomonas aeruginosastrains. HPA3NT3-A2 was developed from a desirable analogue peptide, HPA3NT3, derived from residues 2–20 of the Helicobacter pyloriribosomal protein L1. HPA3NT3-A2 showed stronger activity against planktonic cells (MIC: 8 μM) compared to ciprofloxacin or tobramycin (>512 μM), and a favorable minimum biofilm inhibition and elimination concentration. This peptide also neutralized LPS; decreased levels of EPS; inhibited the production of pro-inflammatory cytokines in the lung, kidney, and spleen; decreased white blood cell counts; and increased survival among infected mice.