State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China.
J Proteome Res. 2023 Nov 3;22(11):3489-3498. doi: 10.1021/acs.jproteome.3c00365. Epub 2023 Oct 19.
Multidrug-resistant threatens both sustainable aquaculture and human health, but the control measure is still lacking. In this study, we adopted functional proteomics to investigate the molecular mechanism underlying norfloxacin (NOR) resistance in . We found that had a global proteomic shift upon acquisition of NOR resistance, featured with increased expression of siderophore biosynthesis and Fe-hydroxamate transport. Thus, either inhibition of siderophore biosynthesis with salicyl-AMS or treatment with another antibiotic, kitasamycin (Kit), which was uptake through Fe-hydroxamate transport, enhanced NOR killing of NOR-resistant both and . Moreover, the combination of NOR, salicyl-AMS, and Kit had the highest efficacy in promoting the killing effects of NOR than any drug alone. Such synergistic effect not only confirmed and bacterial killing assays but also applicable to other clinic isolates. Thus, our data suggest a proteomic-based approach to identify potential targets to enhance antibiotic killing and propose an alternative way to control infection of multidrug-resistant .
多药耐药性既威胁可持续水产养殖，也威胁人类健康，但目前仍缺乏有效的控制措施。在本研究中，我们采用功能蛋白质组学方法研究了耐诺氟沙星（NOR）的 产生的分子机制。我们发现，在获得 NOR 耐药性后， 发生了全蛋白质组转移，其特征是铁载体生物合成和 Fe-羟肟酸盐转运增加。因此，用水杨酰基-AMS 抑制铁载体生物合成，或用另一种通过 Fe-羟肟酸盐转运摄取的抗生素，吉他霉素（Kit）处理，均可增强 NOR 对 NOR 耐药的 和 的杀伤作用。此外，NOR、水杨酰基-AMS 和 Kit 的联合使用比任何单一药物更能有效地促进 NOR 的杀菌效果。这种协同作用不仅在 和 细菌杀伤实验中得到证实，而且在其他临床 分离株中也同样适用。因此，我们的数据提示了一种基于蛋白质组学的方法来识别增强抗生素杀菌作用的潜在靶标，并提出了一种控制多药耐药性 的替代方法。
