The use of antibiotics has greatly improved the treatment of bacterial infections; however, its abuse and misuse has led to a rapid rise in multidrug-resistant (MDR) bacteria. Therefore, the search for new antimicrobial strategies has become critical. Natural flavonoids, a class of widely existing phytochemicals, have gained significant research interest for their diverse biological activities and antibacterial effects on various drug-resistant bacteria. This review summarizes the latest research progress on flavonoids, with a particular focus on several flavonoids exhibiting certain antibacterial activity, and explores their antibacterial mechanisms, including disruption of cell membranes and cell walls, inhibition of proteins and nucleic acids, interference with signal transduction, suppression of efflux pump activity, and inhibition of biofilm formation and virulence factor production. Additionally, we have reviewed the synergistic combinations of flavonoids with antibiotics, such as the combination of quercetin with colistin or EGCG with tetracycline, which significantly enhance therapeutic efficacy.

Increased antimicrobial resistance requires effective ways to overcome the global challenge of bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). From the emergence of MRSA to its continued evolution, it is important to explore this pathogen from fresh perspectives and develop corresponding coping strategies to counter its growing threat. New coping strategies are continuously emerging, including but not limited to enhancing penetration capabilities or targeting their virulence. This review summarizes the epidemiological characteristics, drug resistance mechanisms, and therapeutic strategies of MRSA that have emerged over the past fifteen years. The focus of this paper is to explore the promising applications and current limitations of novel MRSA control strategies. This review serves as a key resource for treating MRSA infections and discussing novel strategies to overcome bacterial drug resistance.

Piceatannol (PIC) is a natural stilbene extracted from grape skins that exhibits biological activities such as antibacterial, antitumor, and antioxidant activities. The present study was carried out to further investigate the effect of PIC on the antibacterial activity of different antibiotics and to reveal the antibacterial mechanism of PIC. We found that PIC had an inhibitory effect against Staphylococcus aureus (S. aureus); its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 128 μg/mL and 256 μg/ mL, respectively. Additionally, we measured the fractional inhibitory concentration (FIC) of PIC combined with antibiotics via the checkerboard method. The results showed that when PIC and ciprofloxacin (CIP) were combined, they displayed a synergistic effect against S. aureus. Moreover, this synergistic effect was verified by time–kill assays. Further, the results of the membrane permeability assay and proton motive force assay revealed that PIC could enhance the sensitivity of S. aureus to CIP by dissipating the bacterial proton motive force (PMF), particularly the ∆ψ component, rather than increasing membrane permeability. PIC also inhibited bacterial adenosine triphosphate (ATP) synthesis and was less likely to induce bacterial resistance but exhibited slight hemolytic activity on mammalian erythrocytes. In summary, the combination of PIC and CIP is expected to become a new drug combination to combat S. aureus.

Rutin is a widely known plant secondary metabolite that exhibits multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing rutin, and further explored the mechanisms behind this synergy. In vitro antibacterial test results of rutin showed that the ranges of minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) are 0.125–1 and 0.125–2 mg/mL, respectively. However, rutin and amikacin have a significant synergistic effect, with a fractional inhibitory concentration index (FICI) range of 0.1875–0.5. The time bactericidal curve proved that the combination of rutin and amikacin inhibited bacterial growth within 8 h. Scanning electron microscopy (SEM) revealed that a low-dose combination treatment could disrupt the cell membrane of Escherichia coli (E. coli). A comprehensive analysis using alkaline phosphatase (AKP), K⁺, and a protein leakage assay revealed that co-treatment destroyed the cell membrane of E. coli, resulting in the significant leakage of AKP, intracellular K⁺, and proteins. Moreover, confocal laser scanning microscopy (CLSM) and red–green cell ratio analysis indicated severe damage to the E. coli cell membrane following the co-treatment of rutin and amikacin. This study indicates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect, which could significantly control antibiotic resistance.

Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that has been proven to possess various biological activities, including anti-inflammatory, antioxidant, and antitumor properties. This study evaluated the inhibitory effect of FA on the biofilm formation of E. coli through crystal violet (CV) staining and scanning electron microscopy (SEM) and investigated the synergistic effect of FA with antibiotics, using the alamar blue (AB) assay. In addition, the regulatory effect of FA on the transcription of biofilm-related genes was analyzed using qRT-PCR technology. The results showed that FA could significantly inhibit biofilm formation, reduce the production of extracellular polymeric substances (EPS), and weaken bacterial motility, without affecting bacterial growth and metabolic activity. qRT-PCR analysis revealed that FA significantly downregulated the expression of curli-related gene csgD, flagella-related genes (flhC, flhD, and motA), and type I fimbriae gene fimA, while upregulating the transcription of c-di-GMP-related genes (pdeR, pdeA, and dosP). It is noteworthy that FA exhibits significant synergistic antibacterial effects when combined with clinically commonly used antibiotics, including sodium fosfomycin, ceftriaxone, gentamicin, and tetracycline, with the most prominent synergistic effect observed in the combination of FA and sodium fosfomycin. These results confirm that FA possesses notable anti-biofilm activity and novel synergistic antibacterial properties, providing a potential therapeutic strategy for treating E. coli infections.

The spread of multidrug-resistant bacteria around the world is rising, and new antibiotics are urgently needed to address the drug resistance crisis. Natural products have become a focal point in the research and development of antibacterial drugs, owing to their structural diversity and biological activity. Kaempferol, in particular, exhibits a range of biological properties, including antioxidant, antibacterial, and antitumor activities, and holds potential for application across various domains. This review aims to provide a comprehensive overview of the extraction, biosynthesis, and antibacterial activity of kaempferol, as well as to elucidate its antibacterial mechanisms. In addition, we also reviewed the synergistic combination of kaempferol with antibiotics, such as the combination of kaempferol with colistin or penicillin, which significantly improved their therapeutic effect. Finally, the preparation of kaempferol nanoparticles and their applications in antibacterial treatments were discussed.