Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella

Yi, Kaifang; Liu, Shuobo; Liu, Peiyi; Luo, Xing-Wei; Zhao, Jin-Feng; Yan, Fengbin; Pan, Yongchu; Liu, Jianhua; Zhai, Yajun; Hu, Gongzheng

doi:10.1016/j.biopha.2022.112873

Cited by 30 publications

(21 citation statements)

References 35 publications

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“…Interestingly, we found that, for the mouse group for which the tetrandrine and colistin were used in combination, the bacterial load was reduced two-fold compared to treatment with either agent alone. A similar in vivo trend has also been observed against Salmonella , but, in that case, the bacterial load was measured in the spleen and liver tissue, whereas we measured bacterial content in the thighs of mice [ 26 ]. These results indicate that a combination of tetrandrine and colistin could potentially treat localized and systematic infections.…”

Section: Discussionmentioning

confidence: 82%

“…Based on its efflux inhibitor potential, tetrandrine is also considered a drug adjuvant against multiple drug-resistant pathogens to improve the retention of drugs inside bacterial cells to perform antibacterial activity. Previous studies have shown that the synergistic activity of tetrandrine with ethidium bromide, fluconazole, and colistin against methicillin-resistant S. aureus , Candida albicans , and Salmonella species [ 26 , 43 , 44 ]. In the current study, aiming for similar synergism, we analyzed the synergistic activity of tetrandrine with colistin against mcr-1 -harboring E. coli .…”

Section: Discussionmentioning

confidence: 99%

“…The synergistic antibacterial activity of tetrandrine with other drugs has already been reported against Staphylococcus aureus, Mycobacterium smegmatis , and Salmonella species [ 26 ]. It has been reported that tetrandrine has an inhibitory effect on the efflux pump of bacteria, which helps in the absorption and retention of drugs inside the bacterial cells and increases their antibacterial activity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

et al. 2022

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Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

et al. 2022

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“…Colistin combined with other antibiotics or adjuvants can effectively treat colistin-resistant bacteria infection, and also reduce the dose of colistin to reduce toxic and side effects. Yi et al ( 2022 ) report the synergistic activity of tetrandrine combined with colistin against the mcr-1 -positive Salmonella both in vitro and in vivo . The tetrandrine dramatically undermines the efflux pump and PMF function of colistin-resistant bacteria, and enhanced the membrane damage ability of colistin.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Colistin Combined With Isopropoxy Benzene Guanidine Against mcr-1-Positive Salmonella in an Intestinal Infection Model

Kong

Lu²,

Yang³

et al. 2022

Front. Microbiol.

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Plasmid-borne colistin resistance mediated by mcr-1 is a growing problem, which poses a serious challenge to the clinical application of colistin for Gram-negative bacterial infections. Drug combination is one of the effective strategies to treat colistin-resistant bacteria. Here, we found a guanidine compound, namely, isopropoxy benzene guanidine (IBG), which boosted the efficacy of colistin against mcr-1-positive Salmonella. This study aimed to develop a pharmacokinetics/pharmacodynamics (PK/PD) model by combining colistin with IBG against mcr-1-positive Salmonella in an intestinal infection model. Antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the synergistic activity of the combination. PK studies of colistin in the intestine were determined through oral gavage of single dose of 2, 4, 8, and 16 mg/kg of body weight in broilers with intestinal infection. On the contrary, PD studies were conducted over 24 h based on a single dose ranging from 2 to 16 mg/kg. The inhibitory effect Imax model was used for PK/PD modeling. The combination of colistin and IBG showed significant synergistic activity. The AUC0−24h/MIC index was used to evaluate the relationship between PK and PD, and the correlation was >0.9085. The AUC0−24h /MIC targets in combination required to achieve the bacteriostatic action, 3-log10 kill, and 4-log10 kill of bacterial counts were 47.55, 865.87, and 1894.39, respectively. These results can facilitate the evaluation of the use of IBG as a potential colistin adjuvant in the treatment of intestinal diseases in broilers caused by colistin-resistant Salmonella.

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“…PMF is interpreted as the sum of pH difference and membrane potential over bacterial membrane. Combination of colistin and tetrandrine showed synergistic antibacterial activity against colistin-resistant Salmonella in which tetrandrine enhanced the membrane-damaging ability of colistin by undermining the functions of PMF and efflux pumps ( 39 ). Econazole was recently reported to act in combination with conventional antibiotics including ampicillin, ceftazidime, gentamicin, and meropenem to effectively eradicate tolerant bacterial cells by dissipation of transmembrane PMF ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antimicrobial Effect of Colistin in Combination with Econazole against Multidrug-Resistant Acinetobacter baumannii and Its Persisters

et al. 2022

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Findings described in this study constitute concrete evidence that it is possible to significantly enhance the antimicrobial activity of colistin by using an antifungal drug, econazole, as a colistin adjuvant. We showed that this drug combination can kill not only multidrug-resistant A. baumannii but also the tolerant subpopulation of such strains known as persisters, which may cause chronic and recurrent infections in clinical settings.

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Synergistic antibacterial activity of tetrandrine combined with colistin against MCR-mediated colistin-resistant Salmonella

Cited by 30 publications

References 35 publications

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli

Pharmacokinetics and Pharmacodynamics of Colistin Combined With Isopropoxy Benzene Guanidine Against mcr-1-Positive Salmonella in an Intestinal Infection Model

Synergistic Antimicrobial Effect of Colistin in Combination with Econazole against Multidrug-Resistant Acinetobacter baumannii and Its Persisters

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