Isoptericola luteus sp. nov., a novel yellow bacterium isolated from soil.

An aerobic, non-motile, Gram-stain-positive bacterium, designated strain NEAU-Y5T, was isolated from a soil sample collected from Northeast Agricultural University, Heilongjiang province. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-Y5T belonged to the genus and showed high 16S rRNA sequence similarity to Isoptericola variabilis (98.9 %), Isoptericola nanjingensis (98.9 %), Isoptericola cucumis (98.5 %), Isoptericola hypogeus (98.5 %), Isoptericola dokdonensis (98.5 %), Isoptericola jiangsuensis (98.3 %), and Isoptericola halalbus (98.1 %), followed by other members of the genus Isoptericola (<98 %), and phylogenetically clustered with I. dokdonensis and I. jiangsuensis. Strain NEAU-Y5T was found to grow at 4-40 °C (optimum, 28 °C), pH 6.0-12.0 (optimum, pH 7.0), and tolerated 0-6 % NaCl (w/v). The cell-wall peptidoglycan type was l-Lys-d-Asp. The whole-cell hydrolysates contained glucose, galactose, and ribose. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, and glucosamine unknown phospholipid. Major fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. The predominant menaquinone was MK-9(H4). The DNA G+C content was 73.4 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain NEAU-Y5T and the type strains of the genus Isoptericola ranged from 18.6 to 23.5 % and from 77.3 to 81.6 %, respectively. Based on morphological, physiological, chemotaxonomic, and phylogenetic data, as well as digital DNA-DNA hybridization and average nucleotide identity values, the novel strain NEAU-Y5T could be differentiated from its closest relatives. Therefore, the strain represents a novel species of the genus Isoptericola, for which the name Isoptericola luteus sp. nov. is proposed. The type strain is NEAU-Y5T (=CCTCC AA 2019087T=DSM 110637T).

1,3-Disubstituted-1,2,4-triazin-6-ones with potent activity against androgen receptor-dependent prostate cancer cells.

Synthesis and biological evaluation of a small, focused library of 1,3-disubstituted-1,2,4-triazin-6-ones for in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) castration-resistant prostate cancer (CRPC) cells led to highly active compounds with in vitro IC50 values against 22Rv1 cells of <200 nM, and with apparent selectivity for this cell type over PC3 cells. From metabolic/PK evaluations of these compounds, a 3-benzyl-1-(2,4-dichlorobenzyl) derivative had superior properties and showed considerably stronger activity, by nearly an order of magnitude, against AR-dependent LNCaP and C4-2B cells compared to AR-independent DU145 cells. This lead compound decreased AR expression in a dose and time dependent manner and displayed promising therapeutic effects in a 22Rv1 CRPC xenograft mouse model. Computational target prediction and subsequent docking studies suggested three potential known prostate cancer targets: p38a MAPK, TGF-ß1, and HGFR/c-Met, with the latter case of c-Met appearing stronger, owing to close structural similarity of the lead compound to known pyridazin-3-one derivatives with potent c-Met inhibitory activity. RNA-seq analysis showed dramatic reduction of AR signalling pathway and/or target genes by the lead compound, subsequently confirmed by quantitative PCR analysis. The lead compound was highly inhibitory against HGF, the c-Met ligand, which fitted well with the computational target prediction and docking studies. These results suggest that this compound could be a promising starting point for the development of an effective therapy for the treatment of CRPC.

1-Benzyloxy-5-phenyltetrazole derivatives highly active against androgen receptor-dependent prostate cancer cells.

A series of 1-benzyloxy-5-phenyltetrazole derivatives and similar compounds were synthesized and evaluated for their in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) prostate cancer cells. The most active compounds had in vitro IC50 values against 22Rv1 cells of <50 nM and showed apparent selectivity for this cell type over PC3 cells; however, these active compounds had short half-lives when incubated with mouse liver microsomes and/or when plasma concentration was monitored during in vivo pharmacokinetic studies in mice or rats. Importantly, lead compound 1 exhibited promising inhibitory effects on cell proliferation, expression of AR and its splicing variant AR-v7 as well as AR regulated target genes in 22Rv1 cells, which are so called castration-resistant prostate cancer (CRPC) cells, and a 22Rv1 CRPC xenograft tumour model in mice. Structural changes which omitted the N-O-benzyl moiety led to dramatic or total loss of activity and S-benzylation of a cysteine derivative, as a surrogate for in vivo S-nucleophiles, by representative highly active compounds, suggested a possible chemical reactivity basis for this "activity cliff" and poor pharmacokinetic profile. However, representative highly active compounds did not inhibit a cysteine protease, indicating that the mode of activity is unlikely to be protein modification by S-benzylation. Despite our efforts to elucidate the mode of action, the mechanism remains unclear.

KIRA8 attenuates non-alcoholic steatohepatitis through inhibition of the IRE1α/XBP1 signalling pathway.

Endoplasmic reticulum (ER) stress is enhanced in non-alcoholic steatohepatitis (NASH). Among three signalling pathways, the IRE1α/XBP1 signalling pathway is strongly implicated in the pathogenesis of NASH but its significance is still largely uncharacterised. In this report, we constructed a hepatocyte-specific XBP1-Luciferase knock-in mouse model that allows in vivo monitoring of the IRE1α/XBP1 activity in hepatocytes. Using this mouse model, we found that IRE1α/XBP1 was activated within hepatocytes during the pathogenesis of NASH. Significantly, a specific IRE1α kinase-inhibiting RNase attenuator, KIRA8, attenuated NASH in mice. In conclusion, our hepatocyte-specific XBP1 splicing reporter mouse represents a valid model for research and drug development of NASH, which showed that the IRE1α-induced XBP splicing is potentiated in hepatocytes during pathogenesis of NASH. Furthermore, we carried out the proof-of-concept study to demonstrate that the allosteric IRE1α RNase inhibitor serves as a promising therapeutic agent for the treatment of NASH.

Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2.

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1ß was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.

Characterization of the metabolism of aloin A/B and aloesin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.

Extracellular matrix regulates force transduction at VE-cadherin junctions.

Increased tension on VE-cadherin (VE-cad) complexes activates adaptive cell stiffening and local cytoskeletal reinforcement--two key signatures of intercellular mechanotransduction. Here we demonstrate that tugging on VE-cad receptors initiates a cascade that results in downstream integrin activation. The formation of new integrin adhesions potentiates vinculin and actin recruitment to mechanically reinforce stressed cadherin adhesions. This cascade differs from documented antagonistic effects of integrins on intercellular junctions. We identify focal adhesion kinase, Abl kinase, and RhoA GTPase as key components of the positive feedback loop. Results further show that a consequence of integrin involvement is the sensitization of intercellular force transduction to the extracellular matrix (ECM) not by regulating junctional tension but by altering signal cascades that reinforce cell-cell adhesions. On type 1 collagen or fibronectin substrates, integrin subtypes α2ß1 and α5ß1, respectively, differentially control actin remodeling at VE-cad adhesions. Specifically, ECM-dependent differences in VE-cad force transduction mirror differences in the rigidity sensing mechanisms of α2ß1 and α5ß1 integrins. The findings verify the role of integrins in VE-cad force transduction and uncover a previously unappreciated mechanism by which the ECM impacts the mechanical reinforcement of interendothelial junctions.

Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-ß/Smad signaling pathway in breast cancer cells.

Cancer-associated fibroblasts (CAFs) represent one of the main components in the tumor stroma and play a key role in breast cancer progression. Transforming growth factor-ß (TGF-ß) has been established to mediate breast cancer metastasis by regulating the epithelial-mesenchymal transition (EMT) and stemness of cancer cells. Caveolin-1 (CAV-1) is a scaffold protein of caveolae that is related to the proliferation and metabolism of cancer cells. It is now well demonstrated that CAV-1 deficiency in the tumor stroma is positively correlated with distant metastasis, but the mechanism remains unclear. Here, we explore whether CAV-1-deficient fibroblasts play an essential role in the EMT and stemness of breast cancer cells (BCCs) through TGF-ß signaling. We establish a specific small interfering RNA (siRNA) to inhibit CAV-1 expression in fibroblasts and coculture them with BCCs to investigate the effect of CAV­1-deficient fibroblasts and the tumor microenvironment on breast cancer progression. This study refreshingly points out that CAV-1 deficiency in fibroblasts enhances TGF-ß1 secretion and then activates the TGF-ß1/Smad signaling pathway of BCCs, thus promoting the metastasis and stemness of BCCs. Collectively, our findings indicate an unexpected role of CAV-1 deficiency in fibroblasts and the tumor microenvironment as a permissive factor, which is regulated by the TGF-ß1 signaling pathway in BCCs.

Current Knowledge of Long Non-Coding RNA HOTAIR in Breast Cancer Progression and Its Application.

Breast cancer is one of the most devastating cancers with high morbidity and mortality in females worldwide. Breast tumorigenesis and further development present great uncertainty and complexity, and efficient therapeutic approaches still lack. Accumulating evidence indicates HOX transcript antisense intergenic RNA (HOTAIR) is dysregulated in cancers and has emerged as a novel hotspot in the field. In breast cancer, aberrant HOTAIR expression is responsible for advanced tumor progression by regulating multifarious signaling pathways. Besides, HOTAIR may act as competitive endogenous RNA to bind to several microRNAs and suppress their expressions, which can subsequently upregulate the levels of targeted downstream messenger RNAs, thereby leading to further cancer progression. In addition, HOTAIR works as a promising biomarker and predictor for breast cancer patients' diagnosis or outcome prediction. Recently, HOTAIR is potentially considered to be a drug target. Here, we have summarized the induction of HOTAIR in breast cancer and its impacts on cell proliferation, migration, apoptosis, and therapeutic resistance, as well as elucidating the underlying mechanisms. This review aims to provide new insights into investigations between HOTAIR and breast cancer development and inspire new methods for studying the association in depth.

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance.

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

Epidermal growth factor receptor and integrins control force-dependent vinculin recruitment to E-cadherin junctions.

This study reports novel findings that link E-cadherin (also known as CDH1)-mediated force-transduction signaling to vinculin targeting to intercellular junctions via epidermal growth factor receptor (EGFR) and integrins. These results build on previous findings that demonstrated that mechanically perturbed E-cadherin receptors activate phosphoinositide 3-kinase and downstream integrins in an EGFR-dependent manner. Results of this study show that this EGFR-mediated kinase cascade controls the force-dependent recruitment of vinculin to stressed E-cadherin complexes - a key early signature of cadherin-based mechanotransduction. Vinculin targeting requires its phosphorylation at tyrosine 822 by Abl family kinases (hereafter Abl), but the origin of force-dependent Abl activation had not been identified. We now present evidence that integrin activation, which is downstream of EGFR signaling, controls Abl activation, thus linking E-cadherin to Abl through a mechanosensitive signaling network. These findings place EGFR and integrins at the center of a positive-feedback loop, through which force-activated E-cadherin signals regulate vinculin recruitment to cadherin complexes in response to increased intercellular tension.This article has an associated First Person interview with the first author of the paper.

Salt bridges gate α-catenin activation at intercellular junctions.

Cadherin complexes transduce force fluctuations at junctions to activate signals that reinforce stressed intercellular contacts. α-Catenin is an identified force transducer within cadherin complexes that is autoinhibited under low tension. Increased force triggers a conformational change that exposes a cryptic site for the actin-binding protein vinculin. This study tested predictions that salt bridges within the force-sensing core modulate α-catenin activation. Studies with a fluorescence resonance energy transfer (FRET)-based α-catenin conformation sensor demonstrated that each of the salt-bridge mutations R551A and D503N enhances α-catenin activation in live cells, but R551A has a greater impact. Under dynamic force loading at reannealing cell-cell junctions, the R551A mutant bound more vinculin than wild-type α-catenin. In vitro binding measurements quantified the impact of the R551A mutation on the free-energy difference between the active and autoinhibited α-catenin conformers. A 2-µs constant-force, steered molecular dynamics simulation of the core force-sensing region suggested how the salt-bridge mutants alter the α-catenin conformation, and identified a novel load-bearing salt bridge. These results reveal key structural features that determine the force-transduction mechanism and the force sensitivity of this crucial nanomachine.

Direct Imaging of Protein Stability and Folding Kinetics in Hydrogels.

We apply fast relaxation imaging (FReI) as a novel technique for investigating the folding stability and dynamics of proteins within polyacrylamide hydrogels, which have diverse and widespread uses in biotechnology. FReI detects protein unfolding in situ by imaging changes in fluorescence resonance energy transfer (FRET) after temperature jump perturbations. Unlike bulk measurements, diffraction-limited epifluorescence imaging combined with fast temperature perturbations reveals the impact of local environment effects on protein-biomaterial compatibility. Our experiments investigated a crowding sensor protein (CrH2) and phosphoglycerate kinase (PGK), which undergoes cooperative unfolding. The crowding sensor quantifies the confinement effect of the cross-linked hydrogel: the 4% polyacrylamide hydrogel is similar to aqueous solution (no confinement), while the 10% hydrogel is strongly confining. FRAP measurements and protein concentration gradients in the 4% and 10% hydrogels further support this observation. PGK reveals that noncovalent interactions of the protein with the polymer surface are more important than confinement for determining protein properties in the gel: the mere presence of hydrogel increases protein stability, speeds up folding relaxation, and promotes irreversible binding to the polymer even at the solution-gel interface, whereas the difference between the 4% and the 10% hydrogels is negligible despite their large difference in confinement. The imaging capabilities of FReI, demonstrated to be diffraction limited, further revealed spatially homogeneous protein unfolding across the hydrogels at 500 nm length scales and revealed differences in protein properties at the gel-solution boundary.

E-cadherin-mediated force transduction signals regulate global cell mechanics.

This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.

Overwintering of Puccinia striiformis f. tritici on Winter Wheat at Varying Altitudes in Gansu and Qinghai Provinces.

Stripe rust, caused by Puccinia striiformis f. tritici, is an important wheat disease in China. P. striiformis f. sp. tritici overwintering and nonoverwintering regions based on the temperature were described elsewhere ( Shi et al. 2005 ). The temperature limit for P. striiformis f. sp. tritici overwintering is derived from field observations. However, P. striiformis f. sp. tritici has recently been observed to overwinter at sites where overwintering is predicted to be unlikely. We studied P. striiformis f. sp. tritici overwintering across several sites in regions close to or further away from the current P. striiformis f. sp. tritici "overwintering boundary" in China. Plants with P. striiformis f. sp. tritici symptoms and uredinia were tagged in late autumn and moved to the laboratory in early spring the following year for quantification of P. striiformis f. sp. tritici biomass via a quantitative reverse-transcription polymerase chain reaction method and for assessment of P. striiformis f. sp. tritici symptoms and sporulation after incubation in a greenhouse. The molecular method detected P. striiformis f. sp. tritici in leaves and sheath in most samples, much greater than the observed incidence of P. striiformis f. sp. tritici symptoms and sporulation after incubation. Thus, further refinement may been necessary to calibrate this molecular method in order to avoid overestimating P. striiformis f. sp. tritici overwintering potential. Active sporulation (hence, successful overwintering) was observed for all sites except one. Increasing altitude led to decreasing incidence of visible P. striiformis f. sp. tritici symptoms and sporulation; in addition to lower temperatures in high altitudes, wind chill may also explain this negative relationship between P. striiformis f. sp. tritici overwinter potential and altitude. P. striiformis f. sp. tritici sporulation on plants subjected to different treatments (control, two oldest leaves, or all leaves removed) indicated that P. striiformis f. sp. tritici overwinters in young green leaves as latent infection established in late autumn. The present study suggests that using only temperature to predict overwintering potential of P. striiformis f. sp. tritici at a given site is insufficient for mountainous regions.

Effect of Low Temperature and Wheat Winter-Hardiness on Survival of Puccinia striiformis f. sp. tritici under Controlled Conditions.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat worldwide. Understanding the survival of Pst during the overwintering period is critical for predicting Pst epidemics in the spring. Real-time quantitative PCR (qPCR) methods quantifying Pst DNA and RNA (cDNA) were developed and compared for the ability to quantify viable Pst in leaf tissues. Both qPCR of DNA and RNA can provide reliable measurement of viable Pst in plant tissues prior to the late sporulation stage for which qPCR of DNA gave a much higher estimate of fungal biomass than qPCR of RNA. The percentage of Pst biomass that was viable in detached and attached leaves under low temperatures decreased over time. Pst survived longer on attached leaves than on detached leaves. The survival of Pst in cultivars with strong winter-hardiness at 0°C and -5°C was greater than those with weak winter-hardiness. However, such differences in Pst survival among cultivars were negligible at -10, -15 and -20°C. Results indicated that Pst mycelia inside green leaves can also be killed by low temperatures rather than through death of green leaves under low temperatures. The relationship of Pst survival in attached leaves with temperature and winter-hardiness was well described by logistic models. Further field evaluation is necessary to assess whether inclusion of other factors such as moisture and snow cover could improve the model performance in predicting Pst overwintering potential, and hence the epidemic in spring.

Dynamic visualization of α-catenin reveals rapid, reversible conformation switching between tension states.

The cytosolic protein α-catenin is a postulated force transducer at cadherin complexes. The demonstration of force activation, identification of consequent downstream events in live cells, and development of tools to study these dynamic processes in living cells are central to elucidating the role of α-catenin in cellular mechanics and tissue function. Here we demonstrate that α-catenin is a force-activatable mechanotransducer at cell-cell junctions by using an engineered α-catenin conformation sensor based on fluorescence resonance energy transfer (FRET). This sensor reconstitutes α-catenin-dependent functions in α-catenin-depleted cells and recapitulates the behavior of the endogenous protein. Dynamic imaging of cells expressing the sensor demonstrated that α-catenin undergoes immediate, reversible conformation switching in direct response to different mechanical perturbations of cadherin adhesions. Combined magnetic twisting cytometry with dynamic FRET imaging revealed rapid, local conformation switching upon the mechanical stimulation of specific cadherin bonds. At acutely stretched cell-cell junctions, the immediate, reversible conformation change further reveals that α-catenin behaves like an elastic spring in series with cadherin and actin. The force-dependent recruitment of vinculin­a principal α-catenin effector­to junctions requires the vinculin binding site of the α-catenin sensor. In cells, the relative rates of force-dependent α-catenin conformation switching and vinculin recruitment reveal that α-catenin activation and vinculin recruitment occur sequentially, rather than in a concerted process, with vinculin accumulation being significantly slower. This engineered α-catenin sensor revealed that α-catenin is a reversible, stretch-activatable sensor that mechanically links cadherin complexes and actin and is an indispensable player in cadherin-specific mechanotransduction at intercellular junctions.

Super-resolution imaging and tracking of protein-protein interactions in sub-diffraction cellular space.

Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein-protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB-EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB-EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB-EF-Tu interactions.