MtrAB two-component system is crucial for the intrinsic resistance and virulence of Mycobacterium abscessus.

Mycobacterium abscessus (Mab) poses serious therapeutic challenges, largely due to its intrinsic resistance to many antibiotics. The development of targeted therapeutic strategies necessitates the identification of bacterial factors that contribute to its reduced susceptibility to antibiotics and/or to the killing by its host cells. In this study, we discovered that Mab strains with disrupted mtrA, mtrB or both, or a gene-edited mtrA encoding MtrA with Tyr102Cys mutation, exhibited highly increased sensitivity to various drugs compared to the wild-type Mab.

Arbuscular mycorrhizal fungi mitigate cadmium stress in maize.

Soil cadmium (Cd) pollution poses a significant environmental threat, impacting global food security and human health. Recent studies have highlighted the potential of arbuscular mycorrhizal (AM) fungi to protect crops from various heavy metal stresses, including Cd toxicity. To elucidate the tolerance mechanisms of maize in response to Cd toxicity under AM symbiosis, this study used two maize genotypes with contrasting Cd tolerance: Zhengdan958 (Cd-tolerant) and Zhongke11 (Cd-sensitive).

EmbB and EmbC regulate the sensitivity of to echinomycin.

Treatment of (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti-Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH).

Investigating the role of in intrinsic resistance to multiple drugs in .

Unlabelled: The increasing clinical significance of is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat infections. This study is inspired by the drug-hypersensitive profile of a mutant (U14) with transposon insertion in .

From phenotyping to genetic mapping: identifying water-stress adaptations in legume root traits.

Background: Climate change induces perturbation in the global water cycle, profoundly impacting water availability for agriculture and therefore global food security. Water stress encompasses both drought (i.e.

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis.

As an obligate aerobe, relies on its branched electron transport chain (ETC) for energy production through oxidative phosphorylation. Regimens targeting ETC exhibit promising potential to enhance bactericidal activity against and hold the prospect of shortening treatment duration. Our previous research demonstrated that the bacteriostatic drug candidate TB47 (T) inhibited the growth of by targeting the cytochrome complex and exhibited synergistic activity with clofazimine (C).

Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in .

Tuberculosis (TB) is the leading infectious disease caused by and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against and .

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from , as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/-catenin pathway.

Variability in cadmium stress tolerance among four maize genotypes: Impacts on plant physiology, root morphology, and chloroplast microstructure.

Cadmium (Cd) is detrimental to both plants and humans. Maize (Zea mays L.) genotypes exhibit variations in Cd accumulations.

The role of arbuscular mycorrhizal fungi in the alleviation of cadmium stress in cereals: A multilevel meta-analysis.

The symbiotic relationships between crop species and arbuscular mycorrhizal fungi (AMF) are crucial for plant health, productivity, and environmental sustainability. The roles of AMF in reducing crop stress caused by cadmium (Cd) toxicity and in the remediation of Cd-contaminated soil are not fully understood. Here we report on a meta-analysis that sought to identify the functions of AMF in cereals under Cd stress.

Additive screening and formula optimization of microbial inhibitor having disease prevention and growth promotion effects on .

In order to develop environment friendly microbial inhibitor that can also control disease and promote oat () growth, the growth rate method and response surface methodology were used to screen wetting agents, preservatives and protective agents at optimal concentrations in this study. Antagonistic activity of the tested bacterium and cell-free fermentation liquid against pathogenic fungi was evaluated on potato dextrose agar (PDA) substratum plates by dual culture technique. Oxford cup method was used to measure antagonistic reaction between screened bacteria.

3-Methoxy-2-phenylimidazo[1,2-b]pyridazines highly active against Mycobacterium tuberculosis and Mycobacterium marinum.

A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives which were highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm) in an in vitro assay were identified. SAR analysis showed that the most active compounds, which included a phenyl group bearing fluoro substituent(s) at C2, a methoxy function at C3, and a benzyl-heteroatom moiety at C6, exhibited in vitro MIC values generally around 0.63-1.

Synthesis and biological evaluation of 2-(Tetrazol-5-yl)sulfonylacetamides as inhibitors of Mycobacterium tuberculosis and Mycobacterium marinum.

A series of 2-(tetrazol-5-yl)sulfonylacetamide derivatives were synthesized and evaluated for their in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). The most active compounds exhibited in vitro MIC values of 1.25 μg/mL against Mtb, but they were less effective against Mm (MIC ≥ 10 μg/mL).

Structure-Activity Relationship of Novel Pyrimidine Derivatives with Potent Inhibitory Activities against .

Discovery of novel antitubercular drugs is an effective strategy against drug-resistant tuberculosis (TB). Our previous study has identified as a novel antitubercular compound. Herein, we perform a comprehensive structure-activity relationship (SAR) based on , indicating that the central pyrimidine ring moiety was crucial for the antitubercular activities of its derivatives, and replacing the naphthyl group with hydrophobic substitutes was well tolerated.

Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of subsp MF GZ001.

Introduction: Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals.

Genotypic variation in the tolerance to moderate cadmium toxicity among 20 maize genotypes with contrasting root systems.

Background: Cadmium (Cd) contamination in farmland is a serious environmental and safety issue affecting plant growth, crop productivity, and human health. This study aimed to investigate genotypic variation in root morphology and Cd accumulations under moderate Cd stress among diverse maize genotypes. Twenty maize genotypes with contrasting root systems were assessed for Cd tolerance 39 days after transplanting (V6, six-leaf stage) under 20 μmol L CdCl using a semi-hydroponic phenotyping platform in a glasshouse.

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Clinical Isolates Collected in Guangzhou Chest Hospital, China.

Objective: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the gene. We aimed to investigate the prevalence of mutations pattern in the entire gene of clinical isolates and their association with resistance level to RIF.

Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed strains was performed via the proportion method and Bactec MGIT 960 system.

Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus.

Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics available and so can be a nightmare. Mechanisms of its intrinsic resistance remain not fully understood. Here, we selected and confirmed an M.

A Caps-Ubi Model for Protein Ubiquitination Site Prediction.

Ubiquitination, a widespread mechanism of regulating cellular responses in plants, is one of the most important post-translational modifications of proteins in many biological processes and is involved in the regulation of plant disease resistance responses. Predicting ubiquitination is an important technical method for plant protection. Traditional ubiquitination site determination methods are costly and time-consuming, while computational-based prediction methods can accurately and efficiently predict ubiquitination sites.

Transcriptomic and Metabolomic Analyses of the Effects of Exogenous Trehalose on Heat Tolerance in Wheat.

Trehalose can improve the tolerance of plants to various types of environmental stress. Nonetheless, information respecting the molecular networks of wheat seedlings to exogenous trehalose under heat stress is limited. Here, two wheat varieties pretreated with exogenous trehalose were selected to explore the molecular mechanism by which trehalose improves the heat tolerance of wheat ( L.

Stichoposide C Exerts Anticancer Effects on Ovarian Cancer by Inducing Autophagy via Inhibiting AKT/mTOR Pathway.

Purpose: Stichoposide C (STC) is a triterpene glycoside isolated from , which is previously demonstrated to wide spectrum of anticancer effects against various tumor cells. However, the antitumor effects and underlying molecular mechanisms in ovarian cancer (OC) cells are not fully understood. Here, we examined if and through which mechanisms STC exerts anticancer effects on OC.

Nutrients available in the soil regulate the changes of soil microbial community alongside degradation of alpine meadows in the northeast of the Qinghai-Tibet Plateau.

The alpine meadow in the Qinghai-Tibet Plateau has been seriously degraded due to human activities and climate change in recent decades. Understanding the changes of the soil microbial community in response to the degradation process helps reveal the mechanism underlying the degradation process of alpine meadows. We surveyed and analyzed changes of the vegetation, soil physicochemical properties, and soil microbial community in three degradation levels, namely, non-degradation (ND), moderate degradation (MD), and severe degradation (SD), of the alpine meadows in the northeastern Qinghai-Tibet Plateau.

Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for .

Buruli ulcer (BU), caused by , is currently treated with rifampin-streptomycin or rifampin-clarithromycin daily for 8 weeks recommended by World Health Organization (WHO). These options are lengthy with severe side effects. A new anti-tuberculosis drug, TB47, targeting QcrB in cytochrome bc1:aa3 complex is being developed in China.

Rapid visualized assessment of drug efficacy in live mice with a selectable marker-free autoluminescent Klebsiella pneumoniae.

Klebsiella pneumoniae is an opportunistic pathogen that is responsible for community acquired infections and nosocomial infections. Antibiotic-resistant K. pneumoniae and/or hypervirulent K.