Vollenweider Vera, Rehm Karoline, Chepkirui Clara, Pérez-Berlanga Manuela, Polymenidou Magdalini, Piel Jörn, Bigler Laurent, Kümmerli Rolf
Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Department of Chemistry, University of Zurich, Zurich, Switzerland.
Elife. 2024 Dec 18;13:RP92493. doi: 10.7554/eLife.92493.
The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here, we show that the iron-chelating pyoverdines, siderophores produced by environmental spp., have strong antibacterial properties by inducing iron starvation and growth arrest in pathogens. A screen of 320 natural isolates used against 12 human pathogens uncovered several pyoverdines with particularly high antibacterial properties and distinct chemical characteristics. The most potent pyoverdine effectively reduced growth of the pathogens , and in a concentration- and iron-dependent manner. Pyoverdine increased survival of infected host larvae and showed low toxicity for the host, mammalian cell lines, and erythrocytes. Furthermore, experimental evolution of pathogens combined with whole-genome sequencing revealed limited resistance evolution compared to an antibiotic. Thus, pyoverdines from environmental strains have the potential to become a new class of sustainable antibacterials against specific human pathogens.
全球抗生素耐药性的上升促使人们研发针对细菌病原体的新型药物。一种常见的方法是寻找微生物分泌的用于抑制竞争对手的天然化合物。在此，我们表明，环境菌株产生的铁螯合绿脓菌素（一种铁载体）通过诱导病原体铁饥饿和生长停滞而具有强大的抗菌特性。对320种天然分离物针对12种人类病原体进行的筛选发现了几种具有特别高抗菌特性和独特化学特征的绿脓菌素。最有效的绿脓菌素以浓度和铁依赖性方式有效降低了病原体的生长。绿脓菌素提高了受感染宿主幼虫的存活率，并且对宿主、哺乳动物细胞系和红细胞显示出低毒性。此外，病原体的实验进化结合全基因组测序显示，与抗生素相比，耐药性进化有限。因此，环境菌株产生的绿脓菌素有潜力成为针对特定人类病原体的新型可持续抗菌药物。
