Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Authors who have equal contributions for this work.
Version 1 : Received: 10 May 2023 / Approved: 11 May 2023 / Online: 11 May 2023 (05:50:54 CEST)

A peer-reviewed article of this Preprint also exists.

Zhang, L.; Yan, Y.; Zhu, J.; Xia, X.; Yuan, G.; Li, S.; Deng, B.; Luo, X. Quinone Pool, a Key Target of Plant Flavonoids Inhibiting Gram-Positive Bacteria. Molecules 2023, 28, 4972. Zhang, L.; Yan, Y.; Zhu, J.; Xia, X.; Yuan, G.; Li, S.; Deng, B.; Luo, X. Quinone Pool, a Key Target of Plant Flavonoids Inhibiting Gram-Positive Bacteria. Molecules 2023, 28, 4972.

Abstract

Plant flavonoids have increasingly paid a close attention to for new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the gram-positive bacteria, and which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to MKH2, we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminary selected, and their MICs against gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against S. aureus were determined using broth microdilution method, nine compounds with the MICs ranged from 2 to 4,096 μg/mL or more than 1,024 μg/mL were eventually selected, and then their MICs against S. aureus were determined interfered with different concentrations of MK-4 and the MKs extracted from S. aureus. The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase of the interfering concentrations of MK-4 (from 2 to 256 μg/mL) and MK extract (from 4 to 512 μg/mL), and while those, with the MICs equal to or more than 512 μg/mL, decreased a little or remained unchanged. Especially, under the interference of MK-4 (256 μg/mL) and MK extract (512 μg/mL), the MICs of α-mangostin, a compound with greatest inhibitory activity to S. aureus in these twelve plant flavonoids, increased by 16 times and 8 to16 times, respectively. Based on these above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.

Keywords

Flavonoid; Antimicrobial mechanism; Quinone; Menaquinone; Respiratory chain; bacterium; MIC; Staphylococcus aureus; α-Mangostin

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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