Mechanisms Of Resistance Research Articles

Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells

The current study established the first in vitro Encorafenib resistance protocol in BRAF-mutated malignant melanoma (MM) cells and investigated the resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were investigated using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress and iron colorimetric assay. The most resistant group, called A375-R, was determined in the cells treated with a constant dose of 10 nM over 3 months. The viability, apoptosis, and G0/G1 arrest reflected the acquired chemoresistance. Autophagic Beclin and LC3 proteins, and AKT signaling increased in the A375-R. RNA-Seq results also exhibited altered epigenetic regulation of resistance; particularly ferritin family members, ion transport pathways. Then, increased NCOA4, FTH1, and iron levels detected in A375-R suggest that the iron metabolism-related mechanism, such as ferritinophagy, might be triggered, which was supported by TEM and oxidative stress analysis. Iron storage, transport, and ferritinophagy have the promising potential to be targeted for combining with BRAF-targeted therapy to reverse Encorafenib resistance in MM. Moreover, this is the first study evaluating in vitro Encorafenib resistance mechanisms, and we suggest that our findings contribute to improving new drug combinations targeting BRAF and iron metabolism in different MM cells.

A Comprehensive Review on Exploring the Potential of Phytochemicals and Biogenic Nanoparticles for the Treatment of Antimicrobial-Resistant Pathogenic Bacteria.

Antimicrobial resistance (AMR) is an escalating global health concern that results in approximately 700,000 deaths annually owing to drug-resistant infections. It compromises the effectiveness of conventional antibiotics, as well as fundamental medical procedures, such as surgery and cancer treatment. Phytochemicals, natural plant constituents, and biogenic nanoparticles synthesized through biological processes are pharmacological alternatives for supplementing or replacing traditional antibiotics. These natural compounds exhibit a diverse range of bioactive properties, including antibacterial, anti-inflammatory, and antioxidant activities, and have the potential to overcome bacterial resistance mechanisms. However, their limited solubility, bioavailability, and stability have limited their therapeutic potential. Nanotechnology, particularly the utilization of biogenic nanoparticles, offers the potential to overcome these limitations by enhancing the biosafety, stability, and controlled release of phytochemical compounds, thereby enabling a more effective combination of resistant pathogens. This review examines current research on the combinatorial application of phytochemicals and biogenic nanoparticles, with emphasis on their capacity to address AMR. This study presents a novel perspective on the concurrent utilization of phytochemicals and biogenic nanoparticles, which may enhance antibacterial efficacy while mitigating toxicity. This review provides specific and innovative insights into the novelty, sustainability, and eco-friendly aspects of these approaches to address multidrug-resistant infections, highlighting their role in emerging as a transformative strategy for AMR management through the integration of natural and biogenic resources.

Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2- Early Breast Cancer.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.

Comparative In vitro antibacterial activity of nemonoxacin and other fluoroquinolones in correlation with resistant mechanisms in contemporary methicillin-resistant Staphylococcus aureus blood isolates in Taiwan

BackgroundNemonoxacin is a new quinolone with an antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Certain sequence types (STs) have been emerging in Taiwan, including fluoroquinolone-resistant ST8/USA300. It’s an urgent need to determine nemonoxacin susceptibility against ST8/USA300 and other emerging lineages, if any. Additionally, molecular characterization of nemonoxacin resistance among different lineages has yet to be defined.MethodsNon-duplicated MRSA blood isolates from five hospitals during 2019–2020 were collected and genotyped by pulsed-field gel electrophoresis, and further correlated to their STs. Antimicrobial susceptibility testing for all antibiotics was performing by using Sensititre standard panel, except nemonoxacin by using agar dilution method. Selected isolates with nemonoxacin MICs ≥ 0.5 mg/mL were sequenced for quinolone resistance-determining regions (QRDRs).ResultsOverall, 915 MRSA isolates belonged to four major lineages, ST8 (34.2%), ST59 (23.5%), ST239 (13.9%), and clonal complex 45 (13.7%). Two-thirds of tested isolates were non-susceptible to moxifloxacin, especially ST8/USA300 and ST239. Of them, proportions of nemonoxacin non-susceptibility by a tentative clinical breakpoint (tCBP) of 1 µg/mL among four major lineages appeared to be different (P = 0.06) and highest in ST239 (22.2%), followed by ST8/USA300 (13.5%). Among 89 isolates sequenced, 44.1% of ST8 and all ST239 isolates had ≥ 3 amino acid substitutions (AAS) in gyrA/parC (group A) or 2 AAS in gyrA/parC with additional AAS in gyrB/parE (group B). Compared to other AAS patterns, isolates in group A had the greatest non-susceptible proportions to nemonoxacin (86.9%; overall/pair-wised comparisons, P < 0.05).ConclusionsOur study confirmed ST8/USA300 MRSA has disseminated in Taiwan. Using a tCBP defined by a higher parenteral daily dosage, nemonoxacin retained potency against moxifloxacin non-susceptible isolates. Patterns of AAS in QRDRs among different lineages may contribute to difference of nemonoxacin susceptibility.

Transcriptome, miRNA, and degradome sequencing reveal the leaf stripe (Pyrenophora graminea) resistance genes in Tibetan hulless barley

Barley leaf stripe, a disease mainly caused by Pyrenophora graminea (P. graminea) infection, severely affects barley yield and quality and is one of the most widespread diseases in barley production. However, little is known about the underlying molecular mechanisms of leaf stripe resistance. In this study, the transcript expression profiles of normal and infected leaves of resistant Tibetan hulless barley (Hordeum vulgare L. var. nudum Hook. f.) variety Kunlun 14 and susceptible variety Z1141 were analyzed by RNA sequencing (RNA-seq). The results showed a total of 7,669 and 5,943 differentially expressed genes (DEGs) were found in resistant and susceptible Kunlun 14 and Z1141, respectively, with 8,916 DEGs found between Kunlun 14 and Z1141. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the 8,916 DEGs identified many significantly enriched categories and pathways, of which a plant–pathogen interaction pathway, containing a total of 102 genes (100 known genes and two novel genes), was found, that was very important for the study of the leaf stripe resistance mechanism. Using RNA-seq, small RNA sequencing (miRNA-seq) combined with degradome sequencing (degradome-seq), four pairs associated with leaf-stripe miRNAs and target genes were obtained, namely Hvu-miR168-5p and Argonaute1 (HvAGO1), Hvu-novel-52 and growth-regulating factor 6 (HvGRF6), Hvu-miR6195 and chemocyanin-like protein (CLP), and Hvu-miR159b and gibberellin-dependent MYB (GAMYB). Transformation of the important target gene HvAGO1 into Arabidopsis verified that HvAGO1 could against Botrytis cinerea. Then RNA-seq and miRNA-seq of Arabidopsis transformed with overexpressed of HvAGO1 were performed. Based on the above research results, we constructed a Protein-Protein Interaction (PPI) network of barley leaf stripe resistance. This study lays the foundation for the study of the barley leaf stripe resistance mechanism and provides new targets for the genetic improvement of disease-resistant barley varieties.

Lactococcus lactis subsp. Lactis boosts stress resistance and host defense mechanisms in Caenorhabditis elegans.

To investigate the effects of Lactococcus lactis subsp. lactis strains LL100933 and LL12007 on the host defense mechanisms of Caenorhabditis elegans against pathogenic infections and stressors. C. elegans fed a 1:1 mixture of Escherichia coli OP50 and LL100933 (OP50+LL100933) or E. coli OP50 and LL12007 (OP50+LL12007) had significantly higher survivability than the control diet (OP50). Moreover, when OP50+LL100933 and OP50+LL12007 were fed to C. elegans deficient in daf-16 and pmk-1, survival did not exceed that of control-fed worms under Salmonella infection. Therefore, these strains may enhance the survivability of C. elegans through the p38 MAPK and DAF-16-related pathways. Gene expressions responsible for these enhanced defense responses were estimated using RNA sequencing and gene ontology analysis. The test groups showed significant upregulation of glutathione S-transferase (gsto-1, gst-5, and gst-17), UDP-glucuronyl transferase (ugt-13, ugt-16, and ugt-21), heme-responsive (hrg-4), invertebrate-type lysozyme (ilys-2), and C-type lectin (clec-52) genes compared to those in the control group. L. lactis subsp. lactis LL100933 and LL12007 strains demonstrated promising benefits as probiotics for enhancing host defense mechanisms in C. elegans. L. lactis subsp. lactis (LL100933 and LL12007) is a potential probiotic for boosting host defense against pathogens and other stressors.

Strong and Fireproof Regenerated Wood via a Combined Phosphorylation-Surface Nanofibrillation and Ionic Cross-Linking Strategy.

To reduce the environmental impact of plastics, an increasing number of high-performance sustainable materials have emerged. Among them, wood-based high-performance structural materials have gained growing attention due to their outstanding mechanical and thermal properties. Here, we introduce phosphate groups onto the wood veneers for surface nanofibrillation, effectively altering both the molecular structure and surface morphology of wood, which enhances the interactions between wood veneers and endows the wood with excellent fire resistance properties. With these phosphorylated wood-based building blocks, "chemical welding" structural materials (CWSMs) obtained through chemical cross-linking exhibit excellent mechanical properties. The flexural strength of CWSM reaches 225 MPa, and the modulus reaches 16 GPa, surpassing those of various types of natural wood. At the same time, phosphorylation has endowed CWSM with excellent fire resistance, with a limiting oxygen index reaching 49%, making it completely noncombustible. More importantly, as a biomass-based structural material, CWSM exhibits mechanical, thermal, and fire resistance properties and degradability far superior to those of traditional petroleum-based plastics, making it an ideal candidate for plastic replacement.

High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations

A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique – Quantitative Mutational Scan sequencing (QMS-seq) – that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E. coli strains exposed to ciprofloxacin, cycloserine, or nitrofurantoin and identify 812 resistance mutations, many in genes and regulatory regions not previously associated with resistance. We find that multi-drug and antibiotic-specific resistance are acquired through categorically different types of mutations, and that minor genotypic differences significantly influence evolutionary routes to resistance. By quantifying mutation frequency with single base pair resolution, QMS-seq informs about the underlying mechanisms of resistance and identifies mutational hotspots within genes. Our method provides a way to rapidly screen for resistance mutations while assessing the impact of multiple confounding factors.

Aptamer-Proximity Ligation Coupled with Rolling Circle Amplification Strategy for an Ultrasensitive Analysis of Tumor-Derived Extracellular Vesicles PD-L1.

Tumor-derived extracellular vesicles (T-EVs) PD-L1 are an important biomarker for predicting immunotherapy response and can help us understand the mechanism of resistance to immunotherapy. However, this is due to the interference from a large proportion of nontumor-derived EVs. It is still challenging to accurately analyze T-EVs PD-L1 in complex human fluids. Herein, a simple and ultrasensitive method based on the dual-aptamer-proximity ligation assay (PLA)-guided rolling circle amplification (RCA) for the analysis of T-EVs PD-L1 was developed. First, dual aptamers with strong binding affinity were utilized for the recognition of EpCAM and PD-L1 on EVs, and then the aptamer-based PLA occurred. With the aid of the high signal amplification ability of RCA guided by the dual-aptamer-based PLA and efficient magnetic separation, the biosensor could realize highly sensitive quantification of EpCAM and PD-L1 dual-positive EVs with a low detection limit of 7.5 particles/μL. In addition, this method based on the aptamer-PLA-guided RCA was used to discriminate cancer patients from healthy donors with 100% accuracy without additional purification. Overall, this strategy might provide a practical tool for the analysis of multiple proteins on EVs, exhibiting great potential in early cancer diagnosis and treatment.

Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation.

Refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a major therapeutic challenge due to its resistance to standard treatments. Engineered T-cells, especially Chimeric Antigen Receptor (CAR) T-cells, have shown promise in overcoming drug resistance. This study investigates the effectiveness of WEE1-engineered T-cells in targeting and eliminating refractory DLBCL in vitro. CAR T-cells were created by transducing a 5th-generation CAR construct designed to recognize WEE1, a surface antigen commonly found on refractory DLBCL cells. The cytotoxic effect of engineered T-cells was tested against Rituximab-resistant DLBCL cells (RR-NU-DUL-1). Apoptosis and cell cycle were evaluated using flow cytometry. Quantitative Real-time PCR (RT-PCR) was used to measure the expression of WEE1, BCL2, and CDK2. The results showed a significant increase in target cell lysis, apoptosis, and necrosis, a significant reduction in the percentage of cells in the G2M phase of the cell cycle, as well as a decrease in gene expression level, indicating strong anti-tumor activity. These findings suggest that CAR T-cell therapy holds great promise for treating refractory DLBCL, offering a potential path for clinical application. This in vitro evaluation highlights the potential of WEE1-engineered T-cells as a targeted treatment strategy for refractory DLBCL, emphasizing their clinical applicability and ability to overcome resistance mechanisms in this aggressive lymphoma subtype.

It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.

The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to the aggressive nature of glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due to the emergence of resistance mechanisms. This review investigates how inhibition of the RTK/Ras/Raf/MEK/ERK pathway alters transcription factors, contributing to acquired resistance mechanisms in GBM. It also highlights the critical role of transcription factor dysregulation in therapeutic resistance. Findings from key studies on the RTK/Ras/Raf/MEK/ERK pathway in GBM were synthesized to explore the role of transcription factor dysregulation in resistance to targeted therapies, radiation, and chemotherapy. The review highlights that transcription factors undergo significant dysregulation following RTK/Ras/Raf/MEK/ERK pathway inhibition, contributing to therapeutic resistance. Transcription factors are promising targets for overcoming treatment resistance in GBM, with cotreatment strategies combining RTK/Ras/Raf/MEK/ERK pathway inhibitors and transcription factor-targeted therapies presenting a novel approach. Despite the challenges of targeting complex structures and interactions, advancements in drug development and precision technologies hold great potential. Continued research is essential to refine these strategies and improve outcomes for GBM and other aggressive cancers.

Natural fiber‐reinforced light composites for the automotive industry

AbstractA European Directive on End‐of‐Life Vehicles (ELVs) established minimum reuse and recovery thresholds of automotive materials based on the weight of the vehicle, to improve fuel efficiency and therefore reduce the CO2 emissions. However, to replace a virgin material, recycled materials must guarantee adequate properties. In this work, low‐density lignocellulosic materials were adopted as “green” reinforcement for recycled polypropylene. In particular, variations in density, thermal resistance, mechanical properties, moldability, and thermal conductivity of a recycled polypropylene (PP) compounded with cork, hazelnut shells, and hazelnut skins (i.e. the cuticle that wraps the fruit inside the shell) were evaluated. The experimental results showed an improvement in thermal resistance and mechanical resistance at high temperatures, without substantially altering the density and thermal conductivity of PP. Among the various fillers analyzed, hazelnut skins seem to give the best results in terms of thermal and mechanical resistance and moldability.Highlights Cork, hazelnut skin and shell stand out as low‐density natural fillers for recycled polypropylene All the natural fillers increase the thermal stability of polypropylene The low‐density fillers enhance the mechanical properties of polypropylene at high temperatures Fillers do not substantially alter the density and thermal conductivity of polypropylene The addition of hazelnut skins allows an enhancement of the moldability of polypropylene

Adaptation of clinical bacteriology techniques for remote polar research.

Antimicrobial resistance (AMR) represents one of the key global public health threats currently facing humanity. The recent UN High-Level Meeting on AMR highlighted the need for greater knowledge generation on its environmental aspects while also considering the potential adverse effects of climate change. The polar regions of the world offer a unique opportunity for AMR research in a near-pristine environment while also holding the potential for novel resistance mechanisms and/or antimicrobial peptide discovery within melting permafrost or glacial ice. Despite considerable technological advances in microbiology, operating in severe cold environments continues to present significant operational challenges. Our report here offers a basis for adaptations to enable both environmental and clinical antimicrobial resistance, microbiome, and discovery research for operating in the harshest of remote environments.

Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens.

A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential. This review will focus on recent studies of metabolism-mediated mechanisms of colonization resistance and virulence strategies enteric pathogens use to overcome them, along with how induction of inflammation by pathogenic bacteria changes the landscape of the gut and enables alternative metabolic pathways. We will focus on how intestinal pathogens counteract the protective effects of microbiota-derived metabolites to illustrate the growing appreciation of how metabolic factors may serve as crucial virulence determinants and overcome colonization resistance.

Clonal Spread and Genetic Mechanisms Underpinning Ciprofloxacin Resistance in Salmonella enteritidis

Salmonella enteritidis is a major cause of foodborne illness worldwide, and the emergence of ciprofloxacin-resistant strains poses a significant threat to food safety and public health. This study aimed to investigate the prevalence, spread, and mechanisms of ciprofloxacin resistance in S. enteritidis isolates from food and patient samples in Shanghai, China. A total of 1625 S. enteritidis isolates were screened, and 34 (2.1%) exhibited resistance to ciprofloxacin. Pulsed-field gel electrophoresis (PFGE) results suggested that clonal spread might have persisted among these 34 isolates in the local area for several years. Multiple plasmid-mediated quinolone resistance (PMQR) genes, GyrA mutations in the quinolone resistance-determining region (QRDR), and overexpression of RND efflux pumps were identified as potential contributors to ciprofloxacin resistance. PMQR genes oqxAB, qnrA, qnrB, and aac(6’)-Ib-cr as well as GyrA mutations S83Y, S83R, D87Y, D87G, D87N, and S83Y-D87Y were identified. The co-transfer of the PMQR gene oqxAB with the ESBL gene blaCTX-M-14/55 on an IncHI2 plasmid with a size of ~245 kbp was observed through conjugation, highlighting the role of horizontal gene transfer in the dissemination of antibiotic resistance. Sequencing of the oqxAB-bearing plasmid p12519A revealed a 248,746 bp sequence with a typical IncHI2 backbone. A 53,104 bp multidrug resistance region (MRR) was identified, containing two key antibiotic resistance determinants: IS26-oqxR-oqxAB-IS26 and IS26-ΔISEcp1-blaCTX-M-14-IS903B. The findings of this study indicate that ciprofloxacin-resistant S. Enteritidis poses a significant threat to food safety and public health. The persistence of clonal spread and the horizontal transfer of resistance genes highlight the need for enhanced surveillance and control measures to prevent the further spread of antibiotic resistance.

Targeting MXD1 sensitises pancreatic cancer to trametinib

BackgroundThe resistance of pancreatic ductal adenocarcinoma (PDAC) to trametinib therapy limits its clinical use. However, the molecular mechanisms underlying trametinib resistance in PDAC remain unclear.ObjectiveWe aimed to illustrate the mechanisms...

Tuning resistive switching behavior and conduction mechanism in Se₈₀Te₂₀ alloy with Fe, Co, Ni, and Cu additives

Tuning resistive switching behavior and conduction mechanism in Se₈₀Te₂₀ alloy with Fe, Co, Ni, and Cu additives

MET Activation in Lung Cancer and Response to Targeted Therapies

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that mediates the activity of a variety of downstream pathways upon its activation. These pathways regulate various physiological processes within the cell, including growth, survival, proliferation, and motility. Under normal physiological conditions, this allows MET to regulate various development and regenerative processes; however, mutations resulting in aberrant MET activity and the consequent dysregulation of downstream signaling can contribute to cellular pathophysiology. Mutations within MET have been identified in a variety of cancers and have been shown to mediate tumorigenesis by increasing RTK activity and downstream signaling. In lung cancer specifically, a number of patients have been identified as possessing MET alterations, commonly receptor amplification (METamp) or splice site mutations resulting in loss of exon 14 (METex14). Due to MET’s role in mediating oncogenesis, it has become an attractive clinical target and has led to the development of various targeted therapies, including MET tyrosine kinase inhibitors (TKIs). Unfortunately, these TKIs have demonstrated limited clinical efficacy, as patients often present with either primary or acquired resistance to these therapies. Mechanisms of resistance vary but often occur through off-target or bypass mechanisms that render downstream signaling pathways insensitive to MET inhibition. This review provides an overview of the therapeutic landscape for MET-positive cancers and explores the various mechanisms that contribute to therapeutic resistance in these cases.

Epigenetic modifications and metabolic gene mutations drive resistance evolution in response to stimulatory antibiotics.

The antibiotic resistance crisis, fueled by misuse and bacterial evolution, is a major global health threat. Traditional perspectives tie resistance to drug target mechanisms, viewing antibiotics as mere growth inhibitors. New insights revealed that low-dose antibiotics may also serve as signals, unexpectedly promoting bacterial growth. Yet, the development of resistance under these conditions remains unknown. Our study investigated resistance evolution under stimulatory antibiotics and uncovered new genetic mechanisms of resistance linked to metabolic remodeling. We documented a shift from a fast, reversible mechanism driven by methylation in central metabolic pathways to a slower, stable mechanism involving mutations in key metabolic genes. Both mechanisms contribute to a metabolic profile transition from glycolysis to rapid gluconeogenesis. In addition, our findings demonstrated that rising environmental temperatures associated with metabolic evolution accelerated this process, increasing the prevalence of metabolic gene mutations, albeit with a trade-off in interspecific fitness. These findings expand beyond the conventional understanding of resistance mechanisms, proposing a broader metabolic mechanism within the selective window of stimulatory sub-MIC antibiotics, particularly in the context of climate change.

TaSnRK3.23B, a CBL-interacting protein kinase of wheat, confers drought stress tolerance by promoting ROS scavenging in Arabidopsis

BackgroundSucrose non-fermenting-1-related protein kinases (SnRKs) have been implicated in plant growth and stress responses. Although SnRK3.23 is known to be involved in drought stress, the underlying mechanism of resistance differs between Arabidopsis and rice, and little is known about its function in wheat.ResultsIn the current work, TaSnRK3.23B was detected on the cell membrane and in the nucleus. TaSnRK3.23B overexpression in Arabidopsis promoted reactive oxygen species (ROS) scavenging via the accumulation of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) and then conferred significant tolerance to drought. The prediction analysis, yeast two-hybrid, and bimolecular fluorescence complementation (BiFC) assays revealed that TaSnRK3.23B interacted with TaCBL2B and TaCBL6B, which are calcineurin B-like (CBL) proteins. The predicted model demonstrated that TaSnRK3 subfamily proteins participate in Ca2+ signaling mediated by TaCBL2B/TaCBL6B and subsequently provide drought stress tolerance by promoting ROS scavenging in wheat.ConclusionsAltogether, the obtained findings contribute to a better understanding of the functions of SnRK3.23 in wheat and offer genetic suggestions for improving drought resistance of wheat.