Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type.

Purpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin. Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations. Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection. Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.

Direct Dioxygen Radical Coupling Driven by Octahedral Ruthenium-Oxygen-Cobalt Collaborative Coordination for Acidic Oxygen Evolution Reaction.

The acidic oxygen evolution reaction (OER) has long been the bottleneck of proton exchange membrane water electrolyzers given its harsh oxidative and corrosive environments. Herein, we suggest an effective strategy to greatly enhance both the acidic OER activity and stability of Co3O4 spinel by atomic Ru selective substitution on the octahedral Co sites. The resulting highly symmetrical octahedral Ru-O-Co collaborative coordination with strong electron coupling effect enables the direct dioxygen radical coupling OER pathway. Indeed, both experiments and theoretical calculations reveal a thermodynamically breakthrough heterogeneous diatomic oxygen mechanism. Additionally, the active Ru-O-Co units are well-maintained upon the acidic OER thanks to the electron transfer from surrounding electron-enriched tetrahedral Co atoms via bridging oxygen bonds that suppresses the overoxidation and thus dissolution of active Ru and Co species. Consequently, the prepared catalyst, even with a low Ru mass loading of ca. 42.8 µg cm-2, exhibits an attractive acidic OER performance with a low overpotential of 200 mV and a low potential decay rate of 0.45 mV h-1 at 10 mA cm-2. Our work suggests an effective strategy to significantly enhance both the acidic OER activity and stability of low-cost electrocatalysts.

Effect of Different Cooking Methods on the Bioactive Components, Color, Texture, Microstructure, and Volatiles of Shiitake Mushrooms.

The effects of different cooking methods (steaming, boiling, air frying, and oven baking) and cooking times (0, 5, 10, 15, and 20 min) on the bioactive components (total phenol, total flavonoid, crude polysaccharides, and eritadenine), color, texture, microstructure, and volatiles in shiitake mushrooms were investigated in this study. Steaming, boiling, and air frying for 5-20 min could decrease the contents of all the four bioactive components in the shiitake mushroom. However, oven baking for 5 min and 10 min showed the highest contents of total phenolics and total flavonoids, respectively. Moreover, the lowest losses of crude polysaccharides and eritadenine were observed for oven baking for 5 min and 15 min, respectively. The lightness of shiitake mushrooms was decreased by all treatments; however, steaming could keep a higher brightness compared with other methods. The microstructure was damaged by all cooking methods, especially air frying for 20 min. Meanwhile, steaming for 20 min decreased the hardness mostly, and there was no significant difference with air frying for 20 min. All cooking treatments decreased the complexity of the flavors and the relative contents of volatile compounds; the lowest contents were found when boiling for 5 min. From these results it can be seen that the physical, histological, and chemical features in shiitake mushroom were influenced by cooking methods and times. In addition, our results provide valuable information for the cooking and processing of shiitake mushrooms and other fungi.

Phenolic profile, antioxidation and anti-proliferation activity of phenolic-rich extracts from Sanghuangporusvaninii.

In this study, phenolic-rich extracts from Sanghuangporus vaninii (SHE) were prepared, the phenolic profile and main phenolic compound content of SHE were studied by UPLC-Orbitrap-MS, and the antioxidant and antiproliferation activities of SHE were evaluated. The results showed that the total polyphenol content and the total flavonoid content of SHE were 42.420 ± 0.011 mg GAE/g EW and 8.504 ± 0.205 mg RE/g EW, respectively. Moreover, 14 phenolic acids and 8 flavonoids in SHE were identified, among which, the major polyphenols were protocatechualdehyde (394.68 µg/g), protocatechuic acid (196.88 µg/g), caffeic acid (96.11 µg/g), L-phenylalanine (12.72 µg/g) and (+)-taxifolin (8.59 µg/g). SHE showed strong radical scavenging, anti-lipid peroxidation and anti-DNA damage capacity in vitro. SHE could effectively induce HepG2 cell apoptosis via the caspases-dependent mitochondrial apoptotic pathway and arrest the cell cycle in the G0/G1 phase. The present study suggested that S. vaninii could be a valuable source of natural antioxidative and antiproliferative ingredients.

Characterization of antibiotic resistance genes and mobile elements in extended-spectrum ß-lactamase-producing Escherichia coli strains isolated from hospitalized patients in Guangdong, China.

AIM: This study aimed to investigate the high-resolution phenotypic and genotypic characterization of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli strains isolated from hospitalized patients to explore the resistance genes and mobile genetic elements (MGEs) involved in horizontal dissemination. METHODS: Between May and September 2021, a total of 216 ESBL-producing E. coli isolates were recovered from multiple departments. The identification of strains was performed using MALDI-TOF mass spectrometry and PCR, while antibiotic susceptibility testing was carried out using the Vitek 2 COMPACT system to determine resistance patterns, while PCR was used to detect different resistance genes and MGEs. In addition, a conjugation assay was performed to investigate the horizontal gene transfer of resistance genes. Selected isolates underwent whole-genome sequencing (WGS) using the Illumina MiSeq platform. RESULTS: A total of 216 out of 409 E. coli isolates recovered from a tertiary hospital were observed to be ESBL-producing, giving a carriage rate of 52.8%, as determined by phenotypic screening. The most frequent sources of ESBL-producing E. coli isolates were urine (129/216, 59.72%) and blood (50/216, 23.14%). The most prevalent ESBL genes identified were blaCTX-M (60.18%), blaTEM (40.27%), and blaSHV (18.05%). Three E. coli isolates were found to carry the genes blaNDM, mcr-1, and fosA3 genes. The most prevalent MGEs were IS26 (95.37%), Int (87.03%), and IncFIB (76.85%). WGS analysis of eight MDR E. coli strains revealed that these isolates belonged to eight different sequence types (STs) and serotypes and were found to harbor multiple plasmid replicons and virulence factors. CONCLUSION: This study highlights a high incidence of antibiotic resistance genes and MGEs associated with the dissemination of ESBLs and other resistance genes.

Mycelial biomass and intracellular polysaccharides production, characterization, and activities in Auricularia auricula-judae cultured with different carbon sources.

The carbon source, an essential factor for submerged culture, affects fungal polysaccharides production, structures, and activities. This study investigated the impact of carbon sources, including glucose, fructose, sucrose, and mannose, on mycelial biomass and the production, structural characterization, and bioactivities of intracellular polysaccharides (IPS) produced by submerged culture of Auricularia auricula-judae. Results showed that mycelial biomass and IPS production varied with different carbon sources, where using glucose as the carbon source produced the highest mycelial biomass (17.22 ± 0.29 g/L) and IPS (1.62 ± 0.04 g/L). Additionally, carbon sources were found to affect the molecular weight (Mw) distributions, monosaccharide compositions, structural characterization, and activities of IPSs. IPS produced with glucose as the carbon source exhibited the best in vitro antioxidant activities and had the strongest protection against alloxan-damaged islet cells. Correlation analysis revealed that Mw correlated positively with mycelial biomass (r = 0.97) and IPS yield (r = 1.00), while IPS antioxidant activities correlated positively with Mw and negatively with mannose content; the protective activity of IPS was positively related to its reducing power. These findings indicate a critical structure-function relationship for IPS and lay the foundation for utilizing liquid-fermented A. aruicula-judae mycelia and the IPS in functional food production.

New insight into the microbiome, resistome, and mobilome on the dental waste water in the context of heavy metal environment.

Object: Hospital sewage have been associated with incorporation of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) into microbes, which is considered as a key indicator for the spread of antimicrobial resistance (AMR). The compositions of dental waste water (DWW) contain heavy metals, the evolution of AMR and its effects on the water environment in the context of heavy metal environment have not been seriously investigated. Thus, our major aims were to elucidate the evolution of AMR in DWW. Methods: DWW samples were collected from a major dental department. The presence of microbial communities, ARGs, and MGEs in untreated and treated (by filter membrane and ozone) samples were analyzed using metagenomics and bioinformatic methods. Results: DWW-associated resistomes included 1,208 types of ARGs, belonging to 29 antibiotic types/subtypes. The most abundant types/subtypes were ARGs of multidrug resistance and of antibiotics that were frequently used in the clinical practice. Pseudomonas putida, Pseudomonas aeruginosa, Chryseobacterium indologenes, Sphingomonas laterariae were the main bacteria which hosted these ARGs. Mobilomes in DWW consisted of 93 MGE subtypes which belonged to 8 MGE types. Transposases were the most frequently detected MGEs which formed networks of communications. For example, ISCrsp1 and tnpA.5/4/11 were the main transposases located in the central hubs of a network. These significant associations between ARGs and MGEs revealed the strong potential of ARGs transmission towards development of antimicrobial-resistant (AMR) bacteria. On the other hand, treatment of DWW using membranes and ozone was only effective in removing minor species of bacteria and types of ARGs and MGEs. Conclusion: DWW contained abundant ARGs, and MGEs, which contributed to the occurrence and spread of AMR bacteria. Consequently, DWW would seriously increase environmental health concerns which may be different but have been well-documented from hospital waste waters.

The physicochemical, antioxidant, hypoglycemic and prebiotic properties of γ-irradiated polysaccharides extracted from Lentinula edodes.

In this study, the influence of γ-irradiation with different dose (0, 4, 8, and 16 kGy) on chemical composition, physicochemical features and bioactivities of polysaccharides extracted from Lentinula edodes (LEP) were investigated. The carbohydrate content (from 59.47 to 70.96%), the solubility, the ⋅OH and DPPH scavenging ability of LEP increased with the increased γ-irradiation dose, while the protein content, the weight-average and number-average molecular weight of LEP were significantly decreased with the increased γ-irradiation dose. Moreover, γ-irradiation treatment caused LEP color changes and surface topography destroyed. γ-Irradiated LEP showed higher hypoglycemic activities in vitro than that of non-irradiated LEP. Moreover, γ-irradiated LEP had better proliferation promoting effects on Lactobacillus rhamnosus and L. plantarum. These results showed that γ-irradiation treatment changes the physicochemical features of LEP, thus affects its antioxidant, hypoglycemic and prebiotic properties, which suggests that γ-irradiated LEP has potential application in the pharmaceutical industries and functional foods. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01234-5.

Transcriptome analysis provides insight into gamma irradiation delaying quality deterioration of postharvest Lentinula edodes during cold storage.

To better determine how gamma irradiation (GI) improves abiotic stress resistance, a transcriptome analysis of postharvest L. edodes in response to 1.0 kGy GI was conducted, and further the underlying mechanism of GI in delaying quality deterioration over 20 d of cold storage was explored. The results suggested that GI was involved in multiple metabolic processes in irradiated postharvest L. edodes. In comparison with the control group, the GI group contained 430 differentially expressed genes, including 151 upregulated genes and 279 downregulated genes, which unveiled characteristic expression profiles and pathways. The genes involved in the pentose phosphate pathway were mainly upregulated and the expression level of the gene encoding deoxy-D-gluconate 3-dehydrogenase was 9.151-fold higher. In contrast, the genes related to other energy metabolism pathways were downregulated. Concurrently, GI inhibited the expression of genes associated with delta 9-fatty acid desaturase, ribosomes, and HSP20; thus, GI helped postpone the degradation of lipid components, suppress transcriptional metabolism and regulate the stress response. Additionally, the metabolic behavior of DNA repair induced by GI intensified by noticeable upregulation. These regulatory effects could play a potential and nonnegligible role in delaying the deterioration of L. edodes quality. The results provide new information on the regulatory mechanism of postharvest L. edodes when subjected to 1.0 kGy GI during cold storage.

Metagenomic evidence for antibiotics-driven co-evolution of microbial community, resistome and mobilome in hospital sewage.

Overconsumption of antibiotics is an immediate cause for the emergence of antimicrobial resistance (AMR) and antibiotic resistant bacteria (ARB), though its environmental impact remains inadequately clarified. There is an urgent need to dissect the complex links underpinning the dynamic co-evolution of ARB and their resistome and mobilome in hospital sewage. Metagenomic and bioinformatic methods were employed to analyze the microbial community, resistome and mobilome in hospital sewage, in relation to data on clinical antibiotic use collected from a tertiary-care hospital. In this study, resistome (1,568 antibiotic resistance genes, ARGs, corresponding to 29 antibiotic types/subtypes) and mobilome (247 types of mobile genetic elements, MGEs) were identified. Networks connecting co-occurring ARGs with MGEs encompass 176 nodes and 578 edges, in which over 19 types of ARGs had significant correlations with MGEs. Prescribed dosage and time-dependent antibiotic consumption were associated with the abundance and distributions of ARGs, and conjugative transfer of ARGs via MGEs. Variation partitioning analyses show that effects of conjugative transfer were most likely the main contributors to transient propagation and persistence of AMR. We have presented the first evidence supporting idea that use of clinical antibiotics is a potent driving force for the development of co-evolving resistome and mobilome, which in turn supports the growth and evolution of ARB in hospital sewage. The use of clinical antibiotics calls for greater attention in antibiotic stewardship and management.

Interface Density Engineering on Heterogeneous Molybdenum Dichalcogenides Enabling Highly Efficient Hydrogen Evolution Catalysis and Sodium Ion Storage.

Constructing active heterointerfaces is powerful to enhance the electrochemical performances of transition metal dichalcogenides, but the interface density regulation remains a huge challenge. Herein, MoO2 /MoS2 heterogeneous nanorods are encapsulated in nitrogen and sulfur co-doped carbon matrix (MoO2 /MoS2 @NSC) by controllable sulfidation. MoO2 and MoS2 are coupled intimately at atomic level, forming the MoO2 /MoS2 heterointerfaces with different distribution density. Strong electronic interactions are triggered at these MoO2 /MoS2 heterointerfaces for enhancing electron transfer. In alkaline media, the optimal material exhibits outstanding hydrogen evolution reaction (HER) performances that significantly surpass carbon-covered MoS2 nanorods counterpart (η10 : 156 mV vs 232 mV) and most of the MoS2 -based heterostructures reported recently. First-principles calculation deciphers that MoO2 /MoS2 heterointerfaces greatly promote water dissociation and hydrogen atom adsorption via the O-Mo-S electronic bridges during HER process. Moreover, benefited from the high pseudocapacitance contribution, abundant "ion reservoir"-like channels, and low Na+ diffusion barrier appended by high-density MoO2 /MoS2 heterointerfaces, the material delivers high specific capacity of 888 mAh g-1 , remarkable rate capability and cycling stability of 390 cycles at 0.1 A g-1 as the anode of sodium ion battery. This work will undoubtedly light the way of interface density engineering for high-performance electrochemical energy conversion and storage systems.

A Hydrazine-Nitrate Flow Battery Catalyzed by a Bimetallic RuCo Precatalyst for Wastewater Purification along with Simultaneous Generation of Ammonia and Electricity.

The traditional technologies for industrial and agricultural effluent treatment are often energy-intensive. Herein, we suggest an electrochemical redox strategy for spontaneous and simultaneous decontamination of wastewater and generation of both fuels and electricity at low cost. Using hydrazine and nitrate effluents as a demonstration, we propose a hydrazine-nitrate flow battery (HNFB) that can efficiently purify the wastewater and meanwhile generate both ammonia fuel and electricity with the assistance of our developed bimetallic RuCo precatalyst. Specifically, the battery delivers a peak power density of 12 mW cm-2 and continuously operates for 20 h with an ammonia yield rate of ca. 0.38 mmol h-1 cm-2 under 100 mA cm-2 . The generated electricity can further drive a hydrazine electrolyzer to produce hydrogen fuel. Our work provides an alternative pathway to purify wastewater and generate high value-added fuels at low cost.

Loss of erm(B)-Mediated rRNA Dimethylation and Restoration of Erythromycin Susceptibility in Erythromycin-Resistant Enterococci Following Induced Linezolid Resistance.

Linezolid has been reported to restore erythromycin susceptibility in erythromycin-resistant Staphylococcus aureus. This phenomenon has not been reported in enterococci and the mechanisms involved therein are still unknown. The purpose of this study was to investigate the mechanisms involved and the effect of combining linezolid with erythromycin on erythromycin-resistant enterococci. Checkerboard techniques were used to determine drug interactions, and 12 of 14 isolates showed a synergistic effect between erythromycin and linezolid (fractional inhibitory concentration <0.5). We observed that the erm(B) gene, which encodes a dimethyltransferase responsible for erythromycin resistance, was expressed from transposon Tn1545 in the tested erythromycin-resistant enterococci. After exposure to linezolid, erm(B)-mediated rRNA dimethylation at A2071 could not be detected, and the erm(B) gene was lost following acquisition of erythromycin susceptibility. Thus, in conclusion, linezolid combined with erythromycin exerts a synergistic effect against erythromycin-resistant enterococci. Linezolid treatment suppressed erm(B)-mediated rRNA dimethylation at A2071, which could lead to loss of the erm(B) gene.

Coexistence of bla NDM-5 and tet(X4) in international high-risk Escherichia coli clone ST648 of human origin in China.

The emergence of pathogens is conferring resistance to last-resort therapies such as tigecycline, colistin, and carbapenems, limiting the therapeutic options, and raising concerns about the emergence of new "superbugs." This study reports the first incident of a bla NDM-5 and tet(X4) co-harboring Escherichia coli with resistance to carbapenem and tigecycline recovered as the causative agent of a urinary tract infection in a 94-year-old patient. The E. coli strain ECCL209 carries multiple resistance genes [i.e., bla TEM-1B , bla NDM-5, bla CMY-2, aadA22, florR, erm(B), mph(A), erm(42), lnuG, qnrS1, and sul2] and exhibits resistance to almost all clinically used antibiotics. MLST analysis found that the strain belongs to ST648, considered a worldwide high-risk pandemic clone. Moreover, multiple plasmid incompatibility types were detected, i.e., IncHI1A, IncHI1B, IncFII, IncFIA, IncFIB, IncQ1, Col, and IncX4. Genetic analysis revealed that bla NDM-5 and tet(X4) genes were localized on two hybrid plasmids with multiple replicons. Continuous monitoring studies are suggested to quantify the antimicrobial resistance and assess the dissemination of such superbugs into a human healthcare setting.

Gastrointestinal digestion, probiotic fermentation behaviors and immunomodulatory effects of polysaccharides from Sanghuangporus vaninii.

In this study, the crude polysaccharides (CSVP) and the preliminary purified polysaccharides (PSVP) from Sanghuangporus vaninii were obtained. The physicochemical properties, gastrointestinal digestion, and probiotic fermentation behaviors of CSVP and PSVP as well as the immunomodulatory effects of PSVP in cyclophosphamide-treated mice were investigated. The results showed that PSVP had higher total polysaccharides content and solubility, but lower radical scavenging activity than CSVP. Moreover, PSVP showed lower hydrolysis degree and better probiotic effects than CSVP. In immunosuppression mice model, PSVP supplement increased the body weight, spleen and thymus index, improved the release of cytokines IFN-γ, immunoglobulins IgM and IgG, and enhanced the lysozyme activity. Moreover, PSVP supplement significantly prevented the oxidative stress in vivo, increased the level of beneficial gut microbiota, especially Bacteroidaceae and Lactobscillsceae, as well as the content of short-chain fatty acids (SCFAs). These results indicated that PSVP could recover the immune response in cyclophosphamide-treated mice by regulating gut microbiota and intestinal barrier. The findings will lay a theoretical foundation for equitable utilization of S. vaninii resources as well as the product development.

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

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.