Raw data for <b>Pyoverdine-antibiotic combination treatment: its efficacy and effects on resistance evolution in </b><b><i>Escherichia coli</i></b>

Antibiotic resistance is a growing concern for global health, demanding innovative and effective strategies to combat pathogenic bacteria. Pyoverdines, iron-chelating siderophores produced by environmental <i>Pseudomonas</i> spp., present a novel class of promising compounds to induce growth arrest in pathogens through iron starvation. While we previously demonstrated the efficacy of pyoverdines as antibacterials, our understanding of how these molecules interact with antibiotics and impact resistance evolution remains unknown. Here, we investigated the propensity of three <i>Escherichia coli</i> strains to evolve resistance against pyoverdine, the cephalosporin antibiotic ceftazidime, and their combination. We used a naive <i>E. coli</i> wildtype strain and two isogenic variants carrying the <i>bla</i>_TEM-1 β-lactamase gene on either the chromosome or a costly multicopy plasmid to explore the influence of genetic background on selection for resistance. We found that strong resistance against ceftazidime and weak resistance against pyoverdine evolved in all <i>E. coli</i> variants under single treatment. Ceftazidime resistance was linked to mutations in outer membrane porin genes (<i>envZ</i> and <i>ompF</i>), whereas pyoverdine resistance was associated with mutations in the oligopeptide permease (<i>opp</i>) operon. In contrast, ceftazidime resistance phenotypes were attenuated under combination treatment, especially for the <i>E. coli</i> variant<i> </i>carrying <i>bla</i>_TEM-1 on the multicopy plasmid. Altogether, our results show that ceftazidime and pyoverdine interact neutrally and that pyoverdine as an antibacterial is particularly potent against plasmid-carrying <i>E. coli </i>strains, presumably because iron starvation compromises both cellular metabolism and plasmid replication.

抗生素耐药性（antibiotic resistance）已成为日益严峻的全球公共卫生关切，亟需创新且有效的策略以对抗病原菌。绿脓菌素（pyoverdine）是环境中假单胞菌属（*Pseudomonas* spp.）产生的铁螯合型铁载体（iron-chelating siderophores），可通过诱导病原菌铁饥饿实现生长阻滞，是一类极具应用前景的新型化合物。尽管此前我们已证实绿脓菌素的抗菌活性，但目前对于这类分子与抗生素的相互作用机制，以及其如何影响耐药性演化的过程仍不甚明晰。本研究针对3株大肠杆菌（*Escherichia coli*）菌株，探究其对绿脓菌素、头孢菌素类抗生素头孢他啶（ceftazidime）以及二者联合用药的耐药性演化倾向。我们采用1株野生型大肠杆菌亲本株，以及2株同基因变异株：二者均携带*bla*_TEM-1 β-内酰胺酶基因，分别整合于染色体或携带于高拷贝数质粒，以此探究遗传背景对耐药性筛选的影响。实验结果显示，在单一药物处理条件下，所有大肠杆菌变异株均演化出对头孢他啶的强耐药性，以及对绿脓菌素的弱耐药性。头孢他啶耐药性与外膜孔蛋白基因（*envZ*与*ompF*）的突变相关，而绿脓菌素耐药性则与寡肽通透酶（opp）操纵子的突变相关。与之相反，联合用药处理时，头孢他啶的耐药表型会被削弱，对于携带高拷贝数质粒*bla*_TEM-1的大肠杆菌变异株尤为显著。综合来看，本研究结果表明头孢他啶与绿脓菌素的相互作用呈中性；且作为抗菌剂的绿脓菌素对携带质粒的大肠杆菌菌株尤为有效，推测其机制为铁饥饿会同时损害细胞代谢与质粒复制。