Antimicrobial resistance seriously threatened human health, and new antimicrobial agents are desperately needed. As one of the largest classes of plant secondary metabolite, flavonoids can be widely found in various parts of the plant, and their antibacterial activities have been increasingly paid attention to. Based on the physicochemical parameters and antibacterial activities of sixty-six flavonoids reported, two regression equations between their ACD/LogP or LogD7.40 and their minimum inhibitory concentrations (MICs) to gram-positive bacteria were established with the correlation coefficients above 0.93, and then were verified by another sixty-eight flavonoids reported. From these two equations, the MICs of most flavonoids against gram-positive bacteria could be roughly calculated from their ACD/LogP or LogD7.40, and the minimum MIC was predicted as approximately 10.2 or 4.8 μM, more likely falls into the range from 2.6 to 10.2 μM, or from 1.2 to 4.8 μM. Simultaneously, both tendentiously concave regression curves indicated that the lipophilicity is a key factor for flavonoids against gram-positive bacteria. Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.
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.
Antimicrobial resistance has emerged as a serious threat to public health. Bacterial biofilm, as a natural lifestyle, is a major contributor to resistance to antimicrobials. Azalomycin F5a, a natural guanidine-containing polyhydroxy macrolide, has remarkable activities against Gram-positive bacteria, including Staphylococcus aureus, a major causative agent of hospital-acquired infections. To further evaluate its potential to be developed as a new antimicrobial agent, its influence on S. aureus biofilm formation was evaluated using the crystal violet method, and then its eradication effect against mature biofilms was determined by confocal laser scanning microscopy, the drop plate method, and regrowth experiments. The results showed that azalomycin F5a could significantly inhibit S. aureus biofilm formation, and such effects were concentration dependent. In addition, it can also eradicate S. aureus mature biofilms with the minimum biofilm eradication concentration of 32.0 μg/mL. As extracellular deoxyribonucleic acid (eDNA) plays important roles in the structural integrity of bacterial biofilm, its influence on the eDNA release in S. aureus biofilm was further analyzed using gel electrophoresis. Combined with our previous works, these results indicate that azalomycin F5a could rapidly penetrate biofilm and causes damages to the cell membrane, leading to an increase in DNase release and eventually eradicating S. aureus biofilm.
Antimicrobial resistance (AMR) poses a serious threat to human health, and new antimicrobial agents are desperate in need. Plant flavonoids have been increasingly paid attention to, for their antibacterial activities, combinational effects on enhancing the antibacterial activity, and reversing the AMR. Based on our previous work, another two regression equations were established once again between the minimum inhibitory concentrations (MICs) (y) and the lipophilicity parameters ACD/LogP or LogD (x). After comparing the fitting goodness of four equations including two published by us, the best one, regarded as the antimicrobial quantitative relationship of plant flavonoids to gram-positive bacteria, was y = -0.1285x6 + 0.7944x5 + 51.785x4 - 947.64x3 + 6638.7x2 - 21273x + 26087, and here x is the LogP value. From this equation, the MICs of most plant flavonoids to gram-positive bacteria can be calculated. The minimum MIC was also predicted as approximately 0.9644 μM, and likely from 0.24 to 0.96 μM. Further, this more reliable equation further proved that the lipophilicity is a key factor of plant flavonoids against gram-positive bacteria. Combined with the antibacterial mechanism suggested in our previous work and the support from recent literature, more intuitive evidence powerfully confirmed the antibacterial mechanism that the cell membrane is the major site of plant flavonoids acting on gram-positive bacteria, and that involving the damage of phospholipid bilayers.
Antimicrobial resistance seriously threatened human health, and new antimicrobial agents are desperately needed. As one of the largest classes of plant secondary metabolite, flavonoids can be widely found in various parts of the plant, and their antibacterial activities have been increasingly paid attention to. Based on the physicochemical parameters and antibacterial activities of sixty-six flavonoids reported, two regression equations between their ACD⁄LogP or LogD7.40 and their minimum inhibitory concentrations (MICs) to gram-positive bacteria were established with the correlation coefficients above 0.93, and then were verified by another sixty-eight flavonoids reported. From these two equations, the MICs of most flavonoids against gram-positive bacteria could be roughly calculated from their ACD⁄LogP or LogD7.40, and their minimum values were respectively predicted as approximately 1.7 or 3.0 μM, more likely fall into the range from 0.9 to 3.4 μM, or from 1.5 to 6.0 μM, respectively. Simultaneously, both tendentiously concave regression curves indicated that the lipophilicity is a key factor for flavonoids against gram-positive. Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.
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