Institute of Global Health of Barcelona, 08036 Barcelona, Spain.
ABAC Therapeutics, 08950 Barcelona, Spain.
Int J Mol Sci. 2021 Dec 12;22(24):13363. doi: 10.3390/ijms222413363.
The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including (SA4-149), (SEP7602), (SPY165), (SAG146), and (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC) of OZN, MOX, LVX, and CIP against type II topoisomerases from .The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones.
抗菌药物耐药性的一个大问题是,需要投入大量精力来设计能够快速达到作用靶点的改良药物。抗生素摄取及其与靶点相互作用的研究是应对这一重大挑战的关键因素。我们研究了奥扎诺星(OZN)、莫西沙星(MOX)、左氧氟沙星(LVX)和环丙沙星(CIP)在 5 个细菌物种中的积累,包括(SA4-149)、(SEP7602)、(SPY165)、(SAG146)和(EF897)。喹诺酮摄取浓度通过琼脂盘扩散生物测定法进行估计。此外,我们还测定了 OZN、MOX、LVX 和 CIP 对 型拓扑异构酶 II 的抑制浓度 50(IC)。与 MOX、LVX 和 CIP 相比,OZN 在所有测试的物种中都能更好地进入细菌细胞内。与 MOX、LVX 和 CIP 相比,OZN 在所有测试的物种中都能更好地进入细菌细胞内。OZN 在接触抗生素的第一分钟内迅速渗透到细胞内,抗生素值在所有菌株中分别为 190 至 447ng/mg(干重)。此外,OZN 对从 中分离的 DNA 回旋酶和拓扑异构酶 IV 显示出所有测试的喹诺酮类药物中最大的抑制活性,IC50 值分别为 10 和 0.5mg/L。OZN 的细胞内浓度明显高于 MOX、LVX 和 CIP。所有这些特征都可以解释 OZN 与其他测试的喹诺酮类药物相比具有更高的体外活性。