Gaálová-Radochová Barbora, Kendra Samuel, Jordao Luisa, Kursawe Laura, Kikhney Judith, Moter Annette, Bujdáková Helena
Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovičova 6, 842 15 Bratislava, Slovakia.
Department of Environmental Health, Research and Development Unit, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisboa, Portugal.
Antibiotics (Basel). 2023 Feb 23;12(3):441. doi: 10.3390/antibiotics12030441.
The natural bioactive molecule farnesol (FAR) is widely studied mainly for its antibiofilm and antimicrobial properties. In addition, it increases the effectiveness of some antimicrobial substances, which makes it interesting for the development of combined therapy. In the present work, the effect of FAR either alone or in combination with oxacillin (OXA) on mixed biofilms formed by clinically relevant pathogens, and , was studied. isolates used for biofilm formation originated from blood cultures and central venous catheters (CVC) were characterized in terms of antimicrobial resistance. The minimal biofilm inhibitory concentration (MBIC) for FAR of 48 h mixed biofilms formed by the and methicillin-sensitive (MSSA) was determined to be 125 μM, and for the mixed biofilms with methicillin-resistant (MRSA) was determined to be 250 μM. Treatment of mixed biofilms with OXA (2 mg/mL) showed ≤4% inhibition; however, the combination of OXA (2 mg/mL) and FAR (300 μM) resulted in 80% inhibition of biofilms. In addition, planktonic cells of exhibited an increased susceptibility to OXA, cefoxitin and kanamycin in the presence of FAR (150 and 300 μM). Scanning electron microscopy (SEM) micrographs confirmed patchy biofilm and lack of candidal hyphae in the samples treated with FAR and FAR/OXA in comparison to control and mixed biofilms treated only with OXA. Intriguingly, in a pilot experiment using fluorescence in situ hybridization (FISH), considerable differences in activity (as indicated by ribosome content) of staphylococcal cells were detected. While the activity rate of the staphylococci in mixed biofilms treated with FAR was high, no FISH-positive signal for staphylococcal cells was found in the biofilm treated with FAR/OXA.
天然生物活性分子法尼醇(FAR)主要因其抗生物膜和抗菌特性而得到广泛研究。此外,它还能提高某些抗菌物质的有效性,这使其在联合疗法的开发中具有吸引力。在本研究中,我们研究了FAR单独或与苯唑西林(OXA)联合使用对由临床相关病原体金黄色葡萄球菌和白色念珠菌形成的混合生物膜的影响。用于生物膜形成的金黄色葡萄球菌分离株源自血培养物,而源自中心静脉导管(CVC)的菌株则根据抗菌药物耐药性进行了表征。由金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌(MSSA)形成的48小时混合生物膜对FAR的最低生物膜抑制浓度(MBIC)确定为125μM,而对于由甲氧西林耐药金黄色葡萄球菌(MRSA)形成的混合生物膜,该浓度则为250μM。用OXA(2mg/mL)处理混合生物膜显示抑制率≤4%;然而,OXA(2mg/mL)和FAR(300μM)联合使用可使生物膜抑制率达到80%。此外,在存在FAR(150和300μM)的情况下,金黄色葡萄球菌的浮游细胞对OXA、头孢西丁和卡那霉素的敏感性增加。扫描电子显微镜(SEM)显微照片证实,与对照和仅用OXA处理的混合生物膜相比,用FAR和FAR/OXA处理的样品中生物膜呈斑驳状且无念珠菌菌丝。有趣的是,在一项使用荧光原位杂交(FISH)的初步实验中,检测到葡萄球菌细胞活性(以核糖体含量表示)存在显著差异。虽然用FAR处理的混合生物膜中葡萄球菌的活性率很高,但在FAR/OXA处理的生物膜中未发现葡萄球菌细胞的FISH阳性信号。