Acinetobacter baumannii is clinically one of the most significant pathogens, especially in intensive care settings, because of its multidrug-resistance (MDR). Repositioning of high-affinity drugs is a faster and more plausible approach for combating the emergence of MDR and to tackle bacterial infections. This study was aimed to evaluate the approved drugs potentially inhibiting A. baumannii PPK1 (AbPPK1) mediated synthesis of polyphosphates (polyP). Based on virtual screening, molecular dynamic simulation, and CD spectroscopy for thermal stability, two stable ligands, etoposide and genistein, were found with promising contours for further investigation. Following in vitro inhibition of AbPPK1, the efficacy of selected drugs was further tested against virulence traits of A. baumannii. These drugs significantly reduced the biofilm formation, surface motility in A. baumannii and led to decreased survival under desiccation. In addition to inhibition of PPK1, both drugs increased the expression of polyP degrading enzyme, exopolyphosphatase (PPX), that might be responsible for the decrease in the total cellular polyP. Since polyP modulates the virulence factors in bacteria, destabilization of the polyP pool by these drugs seems particularly striking for their therapeutic applications against A. baumannii.

鲍曼不动杆菌由于其多药耐药性（MDR），是临床上最重要的病原体之一，尤其是在重症监护环境中。高亲和力药物的重新定位是一种较快且更合理的方法，可用来对抗MDR的出现和细菌感染。这项研究旨在评估批准的潜在抑制鲍曼不动杆菌PPK1（AbPPK1）介导的多磷酸盐合成（polyP）的药物。基于虚拟筛选，分子动力学模拟和CD光谱进行热稳定性分析，发现了两个稳定的配体，依托泊苷和染料木黄酮，它们的轮廓线值得进一步研究。以下体外AbPPK1的抑制，选择药物的功效针对的毒力性状进一步测试鲍曼不动杆菌 这些药物显着减少了鲍曼不动杆菌的生物膜形成和表面运动，并导致干燥下的存活率降低。除了抑制PPK1之外，两种药物均增加了polyP降解酶exopolyphosphatase（PPX）的表达，这可能是导致总细胞polyP减少的原因。由于polyP调节细菌中的毒力因子，因此这些药物对polyP池的破坏作用对于其针对鲍曼不动杆菌的治疗应用似乎尤为突出。