The Antibacterial Activity of Kaempferol Combined with Colistin against Colistin-Resistant Gram-Negative Bacteria

Zhou, Huijing; Xu, Mengxin; Guo, Wenhui; Yao, Zhuocheng; Du, Xin; Chen, Lijiang; Sun, Yao; Shi, Yishi; Cao, Jianming; Zhou, Tieli

doi:10.1128/spectrum.02265-22

Cited by 23 publications

(11 citation statements)

References 30 publications

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“…We further explored the antibiofilm formation capacity of the native structure of kaempferol by performing a minimum biofilm inhibitory concentration (MBIC) assay. We found that kaempferol has a dose-dependent impact on biofilm formation; lower concentrations (<0.05 mM), as previously reported, have minimal effects on biofilm formation 48 , while higher concentrations (0.3 mM) reduce biofilm by >90% compared to the carrier control, without impacting bacterial growth (Fig. 3b ).…”

Section: Resultssupporting

confidence: 84%

“…In a contemporaneous report 48 , the potentiation of colistin by kaempferol was also reported, and it was proposed that the potentiation of colistin by kaempferol against A. baumannii relies on increased membrane permeability. To explore this hypothesis, we investigated the effect of the kaempferol-colistin combination on the integrity of the outer and inner membranes of A. baumannii .…”

Section: Resultsmentioning

confidence: 99%

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Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria

Gadar,

de Dios,

Kadeřábková

et al. 2023

Commun Biol

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Acinetobacter baumannii is a Gram-negative priority pathogen that can readily overcome antibiotic treatment through a range of intrinsic and acquired resistance mechanisms. Treatment of carbapenem-resistant A. baumannii largely relies on the use of colistin in cases where other treatment options have been exhausted. However, the emergence of resistance against this last-line drug has significantly increased amongst clinical strains. In this study, we identify the phytochemical kaempferol as a potentiator of colistin activity. When administered singularly, kaempferol has no effect on growth but does impact biofilm formation. Nonetheless, co-administration of kaempferol with sub-inhibitory concentrations of colistin exposes bacteria to a metabolic Achilles heel, whereby kaempferol-induced dysregulation of iron homeostasis leads to bacterial killing. We demonstrate that this effect is due to the disruption of Fenton’s reaction, and therefore to a lethal build-up of toxic reactive oxygen species in the cell. Furthermore, we show that this vulnerability can be exploited to overcome both intrinsic and acquired colistin resistance in clinical strains of A. baumannii and E. coli in vitro and in the Galleria mellonella model of infection. Overall, our findings provide a proof-of-principle demonstration that targeting iron homeostasis is a promising strategy for enhancing the efficacy of colistin and overcoming colistin-resistant infections.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria

Gadar,

de Dios,

Kadeřábková

et al. 2023

Commun Biol

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“…The identified compounds for A. judaica were reported, with various biological activities, i.e., kaempferol, which is a flavonoid compound, showed success toward the treatment of inflammatory responses, liver injuries, diabetes, malignancy, and obesity [ 30 ]. In addition, a recent study has claimed the promising potential therapeutic use of kaempferol, alone or in combination with colistin, to treat infections caused by drug resistant bacteria [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Phytochemical Characterization and Efficacy of Artemisia judaica Extract Loaded Chitosan Nanoparticles as Inhibitors of Cancer Proliferation and Microbial Growth

et al. 2023

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Despite the advanced development in the field of drug discovery and design, fighting infectious and non-infectious diseases remains a major worldwide heath challenge due to the limited activity of currently used drugs. Nevertheless, in recent years, the approach of designing nanoparticles for therapeutic applications has gained more interest and promise for future use. Thus, the current study is focused on the evaluation of A. judaica extract and chitosan nanoparticles loaded extract (CNPsLE) for potential antimicrobial and anticancer activities. The HPLC analysis of the extract has shown the presence of various phenolic and flavonoid compounds, including kaempferol (3916.34 µg/mL), apigenin (3794.32 µg/mL), chlorogenic acid (1089.58 µg/mL), quercetin (714.97 µg/mL), vanillin (691.55 µg/mL), naringenin (202.14 µg/mL), and rutin (55.64 µg/mL). The extract alone showed higher MIC values against B. subtilis, E. coli, S. aureus, K. pneumonia, and C. albicans (62.5, 15.65, 15.62, 31.25, and 31.25 µg/mL, respectively), whereas lower MIC values were observed when the extract was combined with CNPsLE (0.97, 1.95, 3.9, 4.1, and 15.62 µg/mL, respectively). The extract exhibited low cytotoxicity against normal Vero cells with IC50 173.74 µg/mL in comparison with the cytotoxicity of the CNPsLE (IC50, 73.89 µg/mL). However, CNPsLE showed more selective toxicity against the human prostate cancer cell line (PC3) with IC50 of 20.8 µg/mL than the extract alone with 76.09 µg/mL. In the docking experiments, kaempferol and apigenin were revealed to be suitable inhibitors for prostate cancer (2Q7L). Overall, the obtained data highlighted the promising potential therapeutic use of CNPsLE as an anticancer and antimicrobial agent.

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“…Kaempferol inhibits the PriA helicase (an enzyme crucial for the restart of DNA replication and bacterial survival) activity of S. aureus [31] and displayed efflux pump inhibition in S. aureus with an IC 50 value of 19 µg/mL [21]. In another study, kaempferol exhibited a synergistic effect with colistin against biofilm formation and growth of clinical isolates of colistin-resistant Gram-negative bacteria such as P. aeruginosa, Escherichia coli, K. pneumoniae, and A. baumannii [32]. The observed antibacterial activity was found to be mediated by disrupting the integrity of the cell membrane by kaempferol, which enables the increased interaction of colistin with the lipopolysaccharide of target bacteria.…”

Section: Kaempferolmentioning

confidence: 98%

Phytochemicals as Invaluable Sources of Potent Antimicrobial Agents to Combat Antibiotic Resistance

Jadimurthy

Jagadish

Nayak

et al. 2023

Life

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Plants have been used for therapeutic purposes against various human ailments for several centuries. Plant-derived natural compounds have been implemented in clinics against microbial diseases. Unfortunately, the emergence of antimicrobial resistance has significantly reduced the efficacy of existing standard antimicrobials. The World Health Organization (WHO) has declared antimicrobial resistance as one of the top 10 global public health threats facing humanity. Therefore, it is the need of the hour to discover new antimicrobial agents against drug-resistant pathogens. In the present article, we have discussed the importance of plant metabolites in the context of their medicinal applications and elaborated on their mechanism of antimicrobial action against human pathogens. The WHO has categorized some drug-resistant bacteria and fungi as critical and high priority based on the need to develope new drugs, and we have considered the plant metabolites that target these bacteria and fungi. We have also emphasized the role of phytochemicals that target deadly viruses such as COVID-19, Ebola, and dengue. Additionally, we have also elaborated on the synergetic effect of plant-derived compounds with standard antimicrobials against clinically important microbes. Overall, this article provides an overview of the importance of considering phytogenous compounds in the development of antimicrobial compounds as therapeutic agents against drug-resistant microbes.

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The Antibacterial Activity of Kaempferol Combined with Colistin against Colistin-Resistant Gram-Negative Bacteria

Abstract: COL is one of the few antibiotics effective against clinical isolates of GNB. However, in recent years, GNB resistance to colistin has been increasing.

Cited by 23 publications

References 30 publications

Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria

Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria

Phytochemical Characterization and Efficacy of Artemisia judaica Extract Loaded Chitosan Nanoparticles as Inhibitors of Cancer Proliferation and Microbial Growth

Phytochemicals as Invaluable Sources of Potent Antimicrobial Agents to Combat Antibiotic Resistance

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