Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Different antibacterial modes of plant flavonoids to gram-negative from to -positive bacteria

Version 1 : Received: 1 January 2024 / Approved: 3 January 2024 / Online: 3 January 2024 (03:05:43 CET)
Version 2 : Received: 8 January 2024 / Approved: 8 January 2024 / Online: 9 January 2024 (02:47:50 CET)
Version 3 : Received: 20 February 2024 / Approved: 20 February 2024 / Online: 20 February 2024 (10:48:13 CET)

A peer-reviewed article of this Preprint also exists.

Yan, Y.; Xia, X.; Fatima, A.; Zhang, L.; Yuan, G.; Lian, F.; Wang, Y. Antibacterial Activity and Mechanisms of Plant Flavonoids against Gram-Negative Bacteria Based on the Antibacterial Statistical Model. Pharmaceuticals 2024, 17, 292. https://doi.org/10.3390/ph17030292 Yan, Y.; Xia, X.; Fatima, A.; Zhang, L.; Yuan, G.; Lian, F.; Wang, Y. Antibacterial Activity and Mechanisms of Plant Flavonoids against Gram-Negative Bacteria Based on the Antibacterial Statistical Model. Pharmaceuticals 2024, 17, 292. https://doi.org/10.3390/ph17030292

Abstract

The antibacterial activities of plant flavonoids have increasingly paid a more attention to. The antimicrobial quantitative structure-activity relationship was established for plant flavonoids against gram-positive bacteria, and its major action site was confirmed as the cell membrane in our previous works. To understand whether there are similar antibacterial modes of plant flavonoids against Gram-negative to -positive bacteria, here the minimum inhibitory concentrations (MICs) of thirty-seven plant flavonoids to Escherichia coli were determined using microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD7.40 values and their MICs were analyzed. Combined with those correlations analyses from forty-six plant flavonoids reported, the results showed that there is significantly correlation between their LogP values and MICs to Gram-negative bacteria. However, it is difficult to predict the MICs of plant flavonoids against gram-negative from their lipophilic parameters like against Gram-positive bacteria. After compared the characters of two regression curves established from plant flavonoids against gram-negative and -positive bacteria, it was further found that the antibacterial activities of most plant flavonoids to Gram-negative bacteria are greater than to Gram-positive bacteria when their LogP values are less than about 3.0, but less than which when their LogP values are more than about 3.6. Moreover, different from mainly acting on the cell membrane of Gram-positive bacteria, the comparison of both two curves proposed that there are multiple action modes of plant flavonoids against Gram-negative bacteria, while among them the cell membrane is also an important action site. Combined the analyses for reported data, it was further suggested that the DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Keywords

Flavonoids; Antimicrobial; Lipophilicity; LogP; MIC; Correlation; Bacterium; Escherichia coli; Gram-negative bacteria; mode

Subject

Medicine and Pharmacology, Pharmacy

Comments (1)

Comment 1
Received: 9 January 2024
Commenter: Ganjun Yuan
Commenter's Conflict of Interests: Author
Comment: A new conclusion (it was further suggested that the DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria) was updated, together with thre revised abstract, discussion, and reference of the main manuscript. Moreover,   the supplemetary materials were also updated, and a new Figure (Figure 3) and two Tables S2 and S3 were provided for the conclusion. 
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