Antimicrobial Quantitative Relationship and Mechanism of Plant Flavonoids to Gram-Positive Bacteria

Abstract

Antimicrobial resistance (AMR) poses a serious threat to human health, and new antimicrobial agents are desperately needed. Plant flavonoids are increasingly being paid attention to for their antibacterial activities, for the enhancing of the antibacterial activity of antimicrobials, and for the reversing of AMR. To obtain more scientific and reliable equations, another two regression equations, between the minimum inhibitory concentration (MIC) (y) and the lipophilicity parameter ACD/LogP or LogD7.40 (x), were established once again, based on the reported data. Using statistical methods, the best one of the four regression equations, including the two previously reported, with regard to the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria, is y = −0.1285 x6 + 0.7944 x5 + 51.785 x4 − 947.64 x3 + 6638.7 x2 − 21,273 x + 26,087; here, x is the LogP value. From this equation, the MICs of most plant flavonoids to Gram-positive bacteria can be calculated, and the minimum MIC was predicted as approximately 0.9644 μM and was probably from 0.24 to 0.96 μM. This more reliable equation further proved that the lipophilicity is a key factor of plant flavonoids against Gram-positive bacteria; this was further confirmed by the more intuitive evidence subsequently provided. Based on the antibacterial mechanism proposed in our previous work, these also confirmed the antibacterial mechanism: the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, and this involves the damage of the phospholipid bilayers. The above will greatly accelerate the discovery and application of plant flavonoids with remarkable antibacterial activity and the thorough research on their antimicrobial mechanism.

Quinone Pool, a Key Target of Plant Flavonoids Inhibiting Gram-Positive Bacteria

“…This confirmed again that the lipophilicity is a key factor of plant flavonoids against gram-positive bacteria. Another, according to the rules that the predicted MICs ranged from 1/4× to 4× the determined ones were acceptable [14,15] and those less than 1/8× or more than 8× the determined ones were completely unacceptable, the calculated MIC values of only one plant flavonoid as echinatin was unacceptable, and which once again confirmed the efficiency of equation ( 1) for predicting the MICs of plant flavonoids against gram-positive bacteria.…”

“…Twelve plant flavonoids (Figure 1), with seven structural subtypes including dihydroflavones, flavonols, flavones, isoflavones, chalcones, flavanes and xanthones, were selected for verifying the inference that the quinone pool is a key target of plant flavonoids inhibiting gram-positive bacteria. Their average MICs (or MIC90s) against gram-positive such as S. aureus, S. epidermidis and Bacillus subtilis were calculated according to equation (1) in section 4.3 [15], and the results (Table 1) showed that they had different degrees of inhibitory activities and can be used for further screening to obtain required flavonoids with different antibacterial activities.…”

“…The antimicrobial mechanism of plant flavonoids damaging the phospholipid bilayers of grampositive bacteria was confirmed as above, while other mechanisms acting on the cell membrane should be further explored. As Yuan et al pointed out [14,15], plant flavonoids present nonspecific antimicrobial mechanism. Thereby, the non-enzyme inhibitions of plant flavonoids to the respiratory chain of gram-positive bacteria were also our focus although some probable enzyme mechanisms were likely involved.…”

“…Simultaneously, various antibacterial mechanisms were reported for plant flavonoids [7,9,12], and which was involved the synthesis inhibitions to DNA, proteins and cell envelope, the damage of cell membrane, and so on. Recently, Yuan, et al confirmed that the cell membrane is the major site of plant flavonoids acting on the gram-positive bacteria, and which includes the damage of phospholipid bilayers and likely involves the inhibition of the respiratory chain, or some others [14,15]. Another, they pointed out that the antibacterial activities of plant flavonoids to the grampositive bacteria are directly related to their lipophilicities, and present nonspecific characterization concluded from the antimicrobial quantitative relationships between the physicochemical parameters and the antimicrobial activities [14,15].…”

Prenylated phenolics from Morus alba against MRSA infections as a strategy for wound healing

“…Prenylation facilitates lipophilicity and increases the efficacy of interaction with membrane and target proteins ( Kushwaha et al, 2019 ). For the antimicrobial activity of flavonoids to Gram-positive bacteria, lipophilicity is a key factor ( Yuan et al, 2022 ). Moreover, prenylated flavonoids play an important role in key signaling pathways in the body ( Shi et al, 2021 ).…”