Draveny Margot, Chauvet Hugo, Rouam Valérie, Jamme Frédéric, Masi Muriel
Aix Marseille Univ, INSERM, SSA, MCT, 27 Bd Jean Moulin, Marseille 13005, France.
Synchrotron SOLEIL, L'Orme des Merisiers, Départementale 128, Saint-Aubin 91190, France.
ACS Nano. 2025 Jan 14;19(1):979-988. doi: 10.1021/acsnano.4c12664. Epub 2024 Dec 31.
Bacterial resistance is a major public health challenge. In Gram-negative bacteria, the synergy between multidrug efflux pumps and outer membrane impermeability determines the intracellular concentration of antibiotics. Consequently, it also dictates antibiotic activity on their respective targets. Previous research has employed spectrofluorimetry and synchrotron radiation-based DUV microscopy as tools for monitoring the accumulation of fluoroquinolone antibiotics in bacteria at population and single-cell scales, respectively. Here, we show that cryo-XRF nanoimaging allows intracellular localization and quantification of a fluoroquinolone metal complex accumulation in with different efflux pump expression levels. This method offers a promising avenue for elucidating the intracellular behavior of a range of metallodrugs in bacteria and for designing novel agents with unique mechanisms of action.
细菌耐药性是一项重大的公共卫生挑战。在革兰氏阴性菌中，多药外排泵与外膜通透性之间的协同作用决定了抗生素在细胞内的浓度。因此，它也决定了抗生素对其各自靶点的活性。先前的研究分别采用荧光光谱法和基于同步辐射的深紫外显微镜作为工具，在群体和单细胞水平上监测氟喹诺酮类抗生素在细菌中的积累情况。在这里，我们表明低温X射线荧光纳米成像能够对具有不同外排泵表达水平的细菌中氟喹诺酮金属配合物的积累进行细胞内定位和定量分析。该方法为阐明一系列金属药物在细菌中的细胞内行为以及设计具有独特作用机制的新型药物提供了一条有前景的途径。
