Data from: Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment

Background and objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (a) it reduces the available routes to resistance (since extracellular action precludes any mutations blocking a drug's entry into cells or hastening its exit) and (b) it weakens selection for resistance, since fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically. Methodology: We used gallium to quench the iron-scavenging siderophores secreted and shared among pathogenic Pseudomonas aeruginosa bacteria, and quantitatively monitored its effects on growth in vitro. We assayed virulence in acute infections of caterpillar hosts (Galleria mellonella), and tracked resistance emergence over time using experimental evolution. Results: Gallium strongly inhibited bacterial growth in vitro, primarily via its siderophore quenching activity. Moreover, bacterial siderophore production peaked at intermediate gallium concentrations, indicating additional metabolic costs in this range. In vivo, gallium attenuated virulence and growth – even more so than in infections with siderophore-deficient strains. Crucially, while resistance soon evolved against conventional antibiotic treatments, gallium treatments retained their efficacy over time. Conclusions: Extracellular quenching of bacterial public goods could offer an effective and evolutionarily robust control strategy.研究背景与研究目的：传统抗生素会强力诱导耐药性产生，因此在全球范围内逐渐失效。胞外淬灭共享毒力因子或许是更具前景的防控策略，原因在于：其一，该策略可降低耐药性产生的潜在途径——由于其胞外作用模式，可规避药物进入细胞受阻或加速药物外排这类突变介导的耐药路径；其二，该策略可削弱耐药性选择压力，因为新兴突变体的适合度优势会在协同菌群的所有细胞间被稀释。本研究对该假说进行了实证检验。 研究方法：本研究利用镓淬灭致病性铜绿假单胞菌（Pseudomonas aeruginosa）分泌并共享的铁螯合型铁载体（siderophores），并定量监测其对细菌体外（in vitro）生长的影响。通过大蜡螟（Galleria mellonella）幼虫的急性感染模型测定细菌毒力，并利用实验进化（experimental evolution）体系追踪耐药性随时间的产生情况。 研究结果：镓可通过铁载体淬灭活性，强力抑制细菌的体外生长。此外，细菌铁载体的产生量在镓浓度处于中等水平时达到峰值，表明该浓度区间会带来额外的代谢成本。在体内（in vivo）模型中，镓可减弱细菌的毒力并抑制其增殖，其效果甚至优于铁载体缺陷菌株感染的情况。尤为关键的是，尽管传统抗生素处理组很快便出现了耐药性，但镓处理组的防控效力可随时间保持稳定。 研究结论：对细菌公共物质进行胞外淬灭，有望成为一种高效且在进化层面上具备稳健性的细菌防控策略。