Celiksoy Vildan, Moses Rachael L, Sloan Alastair J, Moseley Ryan, Heard Charles M
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK.
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK.
Pharmaceutics. 2021 Jun 8;13(6):851. doi: 10.3390/pharmaceutics13060851.
Infectious diseases caused by microbial biofilms are a major clinical problem, and new antimicrobial agents that can inhibit biofilm formation and eradicate pre-formed biofilms are urgently needed. Pomegranate extracts are a well-established folkloric medicine and have been used in the treatment of infectious diseases since ancient times, whilst the addition of metal ions, including zinc (II), has enhanced the antimicrobial activity of pomegranate. is generally a non-pathogenic skin commensal bacterium, although it can act as an opportunistic pathogen and cause serious infections, particularly involving catheterization and comorbidities. The aims of this study were to evaluate the holistic activity of pomegranate rind extract (PRE), Zn (II), and PRE/Zn (II) individually and in combination against under both planktonic and biofilm conditions. Antimicrobial activity was detected in vitro using the broth dilution method, and synergistic activity was determined using checkerboard and time-kill assays. Effects on biofilm formation and eradication were determined by crystal violet and BacLight Live/Dead staining. PRE and Zn (II) exerted antimicrobial activity against under both planktonic and biofilm conditions. After 4 h, potent synergistic bactericidal activity was also found when PRE and Zn (II) were co-administered under planktonic conditions (log reductions: PRE 1.83 ± 0.24, Zn (II) 3.4 ± 0.08, and PRE/Zn (II) 6.88 ± 1.02; < 0.0001). In addition, greater heterogeneity was induced in the structure of biofilm using the PRE/Zn (II) combination compared to when PRE and Zn (II) were applied individually. The activity of PRE and the PRE/Zn (II) combination could offer a novel antimicrobial therapy for the treatment of disease-associated infections caused by and potentially other bacteria.
微生物生物膜引起的传染病是一个重大的临床问题,因此迫切需要能够抑制生物膜形成并根除已形成生物膜的新型抗菌剂。石榴提取物是一种公认的民间药物,自古以来就被用于治疗传染病,而添加包括锌(II)在内的金属离子增强了石榴的抗菌活性。表皮葡萄球菌通常是一种非致病性皮肤共生菌,尽管它可作为机会致病菌并引起严重感染,尤其是涉及导管插入术和合并症的感染。本研究的目的是分别评估石榴皮提取物(PRE)、锌(II)以及PRE/锌(II)单独和联合使用对表皮葡萄球菌在浮游和生物膜条件下的整体活性。使用肉汤稀释法体外检测抗菌活性,并使用棋盘法和时间杀菌试验确定协同活性。通过结晶紫和BacLight死活染色确定对生物膜形成和根除的影响。PRE和锌(II)在浮游和生物膜条件下均对表皮葡萄球菌具有抗菌活性。4小时后,在浮游条件下联合使用PRE和锌(II)时也发现了强效的协同杀菌活性(对数减少:PRE 1.83±0.24,锌(II)3.4±0.08,PRE/锌(II)6.88±1.02;P<0.0001)。此外,与单独应用PRE和锌(II)相比,使用PRE/锌(II)组合诱导的表皮葡萄球菌生物膜结构的异质性更大。PRE以及PRE/锌(II)组合的活性可为治疗由表皮葡萄球菌以及可能的其他细菌引起的疾病相关感染提供一种新型抗菌疗法。