Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms.

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.

The antibacterial efficacy of silver diamine fluoride (SDF) is not modulated by potassium iodide (KI) supplements: A study on in-situ plaque biofilms using viability real-time PCR with propidium monoazide.

Silver diamine fluoride (SDF) is commonly used to arrest caries lesions, especially in early childhood caries. Recently, it was suggested that SDF can be combined with potassium iodide (KI) to minimize the discoloration of demineralized dentine associated with SDF application. However, the antibacterial efficacy of SDF alone or combined with KI on in-situ biofilm is unknown. Hence, we compared the anti-plaque biofilm efficacy of two different commercially available SDF solutions, with or without KI, using an in-situ biofilm, analysed using viability real-time PCR with propidium monoazide (PMA). Appliance-borne in-situ biofilm samples (n = 90) were grown for a period of 6 h in five healthy subjects who repeated the experiment on three separate occasions, using a validated, novel, intraoral device. The relative anti-biofilm efficacy of two SDF formulations; 38.0% Topamine (SDFT) and 31.3%, Riva Star (SDFR), KI alone, and KI in combination with SDFR (SDFR+KI) was compared. The experiments were performed by applying an optimized volume of the agents onto the biofilm for 1min, mimicking the standard clinical procedure. Afterwards the viability of the residual biofilm bacteria was quantified using viability real-time PCR with PMA, then the percentage of viable from total bacteria was calculated. Both SDF formulations (SDFT and SDFR) exhibited potent antibacterial activities against the in-situ biofilm; however, there was non-significant difference in their efficacy. KI alone did not demonstrate any antibacterial effect, and there was non-significant difference in the antibacterial efficacy of SDF alone compared to SDF with KI, (SDFT v SDFR/KI). Thus, we conclude that the antibacterial efficacy of SDF against plaque biofilms is not modulated by KI supplements. Viability real-time PCR with PMA was successfully used to analyze the viability of naturally grown oral biofilm; thus, the same method can be used to test the antimicrobial effect of other agents on oral biofilms in future research.