Tabatabaeifar Fatemehalsadat, Isaei Elham, Kalantar-Neyestanaki Davood, Morones-Ramírez José Rubén
Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, UANL, Av. Universidad S/N, San Nicolás de los Garza 66455, Mexico.
Centro de Investigación en Biotecnología y Nanotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Parque de Investigación e Innovación Tecnológica, Km. 10 Autopista al Aeropuerto Internacional Mariano Escobedo, Apodaca 66629, Mexico.
Pharmaceutics. 2022 Dec 20;15(1):4. doi: 10.3390/pharmaceutics15010004.
With the spread of multi-drug-resistant (MDR) bacteria and the lack of effective antibiotics to treat them, developing new therapeutic methods and strategies is essential. In this study, we evaluated the antibacterial and antibiofilm activity of different formulations composed of ibuprofen (IBP), acetylsalicylic acid (ASA), and dexamethasone sodium phosphate (DXP) in combination with ciprofloxacin (CIP), gentamicin (GEN), cefepime (FEP), imipenem (IPM), and meropenem (MEM) on clinical isolates of () and () as well as the transcription levels of biofilm-associated genes in the presence of sub-MICs of IBP, ASA, and DXP. The minimal inhibitory concentrations (MICs), minimal biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) of CIP, GEN, FEP, IPM, and MEM with/without sub-MICs of IBP (200 µg/mL), ASA (200 µg/mL), and DXP (500 µg/mL) for the clinical isolates were determined by the microbroth dilution method. Quantitative real-time-PCR (qPCR) was used to determine the expression levels of biofilm-related genes, including in and in at sub-MICs of IBP, ASA, and DXP. All isolates were methicillin-resistant (MRSA), and all were resistant to carbapenems. IBP decreased the levels of MIC, MBIC, and MBEC for all antibiotic agents in both clinical isolates, except for FEP among isolates. In MRSA isolates, ASA decreased the MICs of GEN, FEP, and IPM and the MBICs of IPM and MEM. In , ASA decreased the MICs of FEP, IPM, and MEM, the MBICs of FEP and MEM, and the MBEC of FEP. DXP increased the MICs of CIP, GEN, and FEP, and the MBICs of CIP, GEN, and FEP among both clinical isolates. The MBECs of CIP and FEP for MRSA isolates and the MBECs of CIP, GEN, and MEM among isolates increased in the presence of DXP. IBP and ASA at 200 µg/mL significantly decreased the transcription level of in , and IBP significantly decreased the transcription level of in . DXP at 500 µg/mL significantly increased the expression levels of and genes in and isolates, respectively. Our findings showed that the formulations containing ASA and IBP have significant effects on decreasing the MIC, MBIC, and MBEC levels of some antibiotics and can down-regulate the expression of biofilm-related genes such as and . Therefore, NSAIDs represent appropriate candidates for the design of new antibacterial and antibiofilm therapeutic formulations.
随着多重耐药（MDR）细菌的传播以及缺乏有效的抗生素来治疗它们，开发新的治疗方法和策略至关重要。在本研究中，我们评估了由布洛芬（IBP）、乙酰水杨酸（ASA）和地塞米松磷酸钠（DXP）与环丙沙星（CIP）、庆大霉素（GEN）、头孢吡肟（FEP）、亚胺培南（IPM）和美罗培南（MEM）组成的不同制剂对（）和（）临床分离株的抗菌和抗生物膜活性，以及在亚抑菌浓度的IBP、ASA和DXP存在下生物膜相关基因的转录水平。通过微量肉汤稀释法测定了CIP、GEN、FEP、IPM和MEM在有/无亚抑菌浓度的IBP（200μg/mL）、ASA（200μg/mL）和DXP（500μg/mL）情况下对临床分离株的最低抑菌浓度（MIC）、最低生物膜抑制浓度（MBIC）和最低生物膜根除浓度（MBEC）。采用定量实时聚合酶链反应（qPCR）来测定在亚抑菌浓度的IBP、ASA和DXP情况下生物膜相关基因的表达水平，包括在（）中的（）和在（）中的（）。所有（）分离株均为耐甲氧西林金黄色葡萄球菌（MRSA），所有（）均对碳青霉烯类耐药。在两种临床分离株中，IBP降低了所有抗生素的MIC、MBIC和MBEC水平，但在（）分离株中FEP除外。在MRSA分离株中，ASA降低了GEN、FEP和IPM的MIC以及IPM和MEM的MBIC。在（）中，ASA降低了FEP、IPM和MEM的MIC、FEP和MEM的MBIC以及FEP的MBEC。DXP增加了两种临床分离株中CIP、GEN和FEP的MIC以及CIP、GEN和FEP的MBIC。在DXP存在的情况下，MRSA分离株中CIP和FEP的MBEC以及（）分离株中CIP、GEN和MEM的MBEC增加。200μg/mL的IBP和ASA显著降低了（）中（）的转录水平，IBP显著降低了（）中（）的转录水平。500μg/mL的DXP分别显著增加了（）和（）分离株中（）和（）基因的表达水平。我们的研究结果表明，含有ASA和IBP的制剂对降低某些抗生素的MIC、MBIC和MBEC水平有显著作用，并且可以下调生物膜相关基因如（）和（）的表达。因此，非甾体抗炎药是设计新型抗菌和抗生物膜治疗制剂的合适候选药物。
