VLX600, an anticancer iron chelator, exerts antimicrobial effects on infections.

presents significant clinical challenges due to its intrinsic and acquired resistance to antibiotics, resulting in prolonged treatments and poor patient outcomes. Addressing the urgent need for novel therapeutics, this study explores the antimicrobial potential of VLX600, originally developed as an anticancer agent, against . Screening a library of 3,200 clinically evaluated compounds identified VLX600 as a potent antimicrobial with minimal cytotoxicity. VLX600 demonstrated inhibitory effects against various strains of with minimum inhibitory concentrations of 4 µg/mL-16 µg/mL. It also remained effective in intracellular in host cells and exhibited broad-spectrum activity against other bacterial species, including , , and . The antimicrobial activity of VLX600 was abrogated by supplemental iron, indicating a mechanism dependent on iron chelation. VLX600 significantly reduced bacterial burdens and inflammation in a murine model of pulmonary infection. Additionally, synergistic effects were observed when VLX600 was combined with conventional antibiotics such as amikacin and clarithromycin . These findings highlight VLX600 as a promising candidate for repurposing as an antimicrobial agent against , warranting further clinical investigations.IMPORTANCE is an opportunistic pathogen that commonly causes pulmonary infections in cystic fibrosis patients. These infections are notoriously difficult to treat due to high levels of antibiotic resistance of , resulting in low cure rates. In this study, we identified a novel antibiotic candidate, VLX600, through high-throughput screening of 3,200 clinical compounds and demonstrated that VLX600 inhibits the growth of by depriving it of ferric and ferrous ions. This study highlights the potential of iron chelators as antimicrobial agents against infections. Since iron is an essential nutrient for the growth of many bacteria, the use of iron chelators could be extended to other infectious diseases. We hope this research will inspire further studies aimed at developing iron chelators as a novel class of antimicrobial agents.