Search Results (69)

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Silicon (Si) protects plants against insect herbivores; however, the underlying mechanisms remain unclear. Polyamines (PAs) play a crucial role in plant–insect interactions. Here, the involvement of Si in putrescine (Put) metabolism and its role in rice resistance against striped stem borer (SSB, Chilo suppressalis Walker) were investigated. The results showed that SSB larval infestation led to a substantial accumulation of free Put in rice seedlings. Si application increased rice resistance against SSB and repressed the SSB attack-induced accumulation of Put, in parallel with a decreased expression of Put biosynthesis genes encoding arginine decarboxylase (ADC1 and ADC2). Moreover, Si application had no significant effect on the wounding-induced expression of ADC1 and ADC2, but attenuated the further elevation in the transcription of ADC1 and ADC2 induced by SSB larvae oral secretion. Simultaneously, Si addition reduced the Put and spermidine contents in SSB-attacked plants. Furthermore, the exogenous application of Put attenuated Si-enhanced resistance against SSB larvae, whereas exogenous D-arginine, an inhibitor of ADC, showed similar effects to Si on rice resistance against SSB. Our findings indicate that Si improves rice resistance to SSB, at least partly by reducing herbivory-stimulated putrescine accumulation. Full article

Black garlic is a thermally processed product derived from fresh garlic through controlled high-temperature and -humidity conditions. During this process, the formation of 5-hydroxymethylfurfural (5-HMF), a potentially harmful byproduct, is a major quality and safety concern in food processing. This study systematically investigated the distributions of 5-HMF and key process-related biochemical components in black garlic samples from three major production regions in China—Jiangsu, Yunnan, and Shandong. Additionally, correlations between 5-HMF and biochemical components—reducing sugars, amino acids, and organic acids—were analyzed to inform process optimization strategies. Results showed significant regional variation in 5-HMF content, with Jiangsu black garlic exhibiting the highest levels, followed by Yunnan and Shandong (p < 0.05). Partial least squares regression analysis (PLSR) indicated that the key biochemical factors regulating 5-HMF accumulation are primarily organic acids. Among them, citric acid was identified as the most important negative regulator (VIP = 3.11). Although acetic acid (VIP = 1.38) and malic acid (VIP = 1.03) showed positive correlations with 5-HMF, aspartic acid (VIP = 0.41) and fructose (VIP = 0.43) exhibited a weak positive correlation, and arginine (VIP = 0.89) showed weak negative correlations, their effects were far less significant than that of citric acid. Based on these findings, we propose a potential strategy for reducing 5-HMF content in black garlic—selecting raw material cultivars with higher endogenous citric acid levels or exploring the exogenous addition and regulation of citric acid during processing. This study provides a theoretical foundation for understanding the accumulation mechanism of 5-HMF in black garlic and suggests new potential regulatory directions for controlling its content. Full article

Yeast cells are passively exposed to ethanol stress during alcoholic fermentation, ultimately impairing cell viability and reducing fermentation efficiency. Arginine, a versatile amino acid, plays a crucial role in regulating cellular responses to various stresses. This study aimed to explore the underlying mechanism by which arginine protects Wickerhamomyces anomalus against ethanol stress. The effects of arginine supplementation (5 mM) under ethanol stress (9% v/v) on cell survival, reactive oxygen species (ROS) production, cellular and mitochondrial membrane integrity, and nitric oxide synthesis were investigated using fluorescent staining methods. Furthermore, differentially expressed genes (DEGs) and metabolites (DEMs) were identified through transcriptomics and metabolomics analyses. The results demonstrated that exogenous arginine enhanced cell survival, reduced ROS levels, maintained cellular and mitochondrial membrane integrity, stimulated nitric oxide production, and modulated gene expression and metabolic pathways involved in pyruvate metabolism, yeast meiosis, fatty acid degradation, glycerophospholipid metabolism, and the biosynthesis of various secondary metabolites. These findings provide intriguing insights into the mechanistic role of arginine in enhancing the tolerance of W. anomalus to ethanol stress, and broaden its application in the fermentation industry for alcoholic beverages. Full article

The strain of Oceanobacillus picturae DY09, as a typical halophilic microorganism, possesses distinctive salt adaptation mechanisms that hold significant application value in the fields of agriculture, industry, and biomedicine. To deeply analyze the salt-tolerance molecular mechanism of this strain, this research disclosed its salt-tolerance strategies under diverse salt concentrations through transcriptomics. In a low-salt environment, the DY09 strain adopted a “metabolic simplification” strategy, significantly reducing the metabolic load by promoting lysine degradation and inhibiting the biosynthesis of branched-chain amino acids and glycine betaine (GB) but upregulating the expression of the GB transporter gene betH and preferentially utilizing exogenous GB to maintain basic osmotic balance. When exposed to high-salt stress, this strain activated multiple regulatory mechanisms: it upregulated the expression of Na⁺/K⁺ antiporter proteins to maintain ionic homeostasis; the synthesis genes of amino acids such as arginine and proline were significantly upregulated, and the GB synthesis genes betA/B and the transporter gene betH were upregulated concurrently, which realized the synergistic operation of endogenous synthesis and exogenous uptake of osmoprotective substances. The expression level of the antioxidant enzyme systems is upregulated to scavenge reactive oxygen species. Simultaneously, the molecular chaperones groES/groEL and GB cooperate to maintain the functional stability of the protein. In this study, a trinity salt-tolerance-integrated strategy of “dynamic perception–hierarchical response–system synergy” of halophilic bacteria was initially proposed, which provided a research idea for exploring the salt–alkali-tolerant mechanism of halophilic bacteria and a theoretical basis for the further development and application of this strain. Full article

Polyamines play a pivotal role in regulating the growth and metabolic adaptation of microalgae, yet their integrative regulatory roles remain underexplored. This review advances a comprehensive perspective of microalgae growth, integrating polyamine dynamics, amino acid metabolism, and redox balance. Polyamines (putrescine, spermidine, and spermine) biology in microalgae, particularly Chlamydomonas reinhardtii, is reviewed, exploring their critical function in modulating cell cycle progression, enzymatic activity, and stress responses through nucleic acid stabilization, protein synthesis regulation, and post-translational modifications. This review explores how the exogenous supplementation of polyamines modifies their intracellular dynamics, affecting growth phases and metabolic transitions, highlighting the complex regulation of internal pools of these molecules. Comparative analyses with Chlorella ohadii and Scenedesmus obliquus indicated species-specific responses to polyamine fluctuations, linking putrescine and spermine levels to important tunable metabolic shifts and fast growth phenotypes in phototrophic conditions. The integration of multi-omic approaches and computational modeling has already provided novel insights into polyamine-mediated growth regulation, highlighting their potential in optimizing microalgae biomass production for biotechnological applications. In addition, genomic-based modeling approaches have revealed target genes and cellular compartments as bottlenecks for the enhancement of microalgae growth, including mitochondria and transporters. System-based analyses have evidenced the overlap of the polyamines biosynthetic pathway with amino acids (especially arginine) metabolism and Nitric Oxide (NO) generation. Further association of the H₂O₂ production with polyamines metabolism reveals novel insights into microalgae growth, combining the role of the H₂O₂/NO rate regulation with the appropriate balance of the mitochondria and chloroplast functionality. System-level analysis of cell growth metabolism would, therefore, be beneficial to the understanding of the regulatory networks governing this phenotype, fostering metabolic engineering strategies to enhance growth, stress resilience, and lipid accumulation in microalgae. This review consolidates current knowledge and proposes future research directions to unravel the complex interplay of polyamines in microalgal physiology, opening new paths for the optimization of biomass production and biotechnological applications. Full article

For marine bacteria, the phycosphere is attractive as a major source of labile nutrients, but it also presents challenges due to the accumulation of stressors, such as reactive oxygen species (ROS) from algal metabolisms. Therefore, successful colonization of bacteria in the phycosphere requires an efficient mechanism to fight against oxidative stress, which is still a missing piece in studying bacteria–algae interactions. Here, we demonstrate that a common metabolite, indole acetic acid (IAA), enables the Roseobacter clade Sulfitobacter mediterraneus SC1-11, an IAA-producer, to resist hydrogen peroxide (H₂O₂) stress and that IAA biosynthesis can be activated by low concentrations of H₂O₂. Proteomics and metabolomics analyses revealed that bacteria consume high amino acid levels when exposed to H₂O₂ stress, while exogenous supplementation with IAA effectively protects bacteria from ROS damage and alleviates amino acid starvation by upregulating several proteins responsible for replication, recombination, and repair, as well as two proteins involved in amino acid transport and metabolism. Furthermore, the supplementation of some amino acids, such as arginine, also showed a significant protective effect on bacteria under H₂O₂ stress. This study highlights an unprecedented role of IAA in regulating amino acid metabolisms for resisting oxidative stress, which may be a specific strategy for adapting to the phycosphere. Full article

Microcystis aeruginosa (M. aeruginosa), a key species in cyanobacterial blooms, is notably concerning due to its production of harmful microcystins (MCs). In this study, the differences in the ability of MC-producing and MC-free strains of M. aeruginosa to respond to the exogenous MCs (MC-LR) were compared. The results showed that at higher concentrations, MC-LR affected cell morphology, cell growth, photosynthetic efficiency, and induced oxidative stress in M. aeruginosa. Under high MC-LR concentration exposure, MC-producing strains showed a 14.7% reduction in cell density, accompanied by a 32% elevation in Vj and a 63.1% decline in F_V/F_M. MC-free strains showed cell density decreasing by 22.5%, Vj increasing 2-fold, and F_V/F_M dropping by 69.5%. The inhibitory effect of MC-LR at higher concentrations was found to be stronger in MC-free compared to MC-producing strains. In addition, MC-LR reduced the efficiency of photosystem II by blocking electron transfer from QA to QB; for MC-free strains, MC-LR may have acted as a signaling molecule affecting the targeting of QB on the D1 protein, thus leading to QB detachment from the protein complex. Metabolomics analysis showed that MC-LR affects arginine synthesis in M. aeruginosa and thus the synthesis and release of MCs. Full article

In recent years, there have been many studies on the response of plants to heavy metal stress, but the metabolic changes in bryophytes, pioneer plants quickly responding to environmental changes, under exogenous cadmium (Cd) stress have yet to be explored. In this indoor experiment, the responses in the metabolome of bryophyte Tortella tortuosa (Hedw.) Limpr. to different Cd exposure levels (0 (CK), 5 (T1), and 10 (T2) mg·L⁻¹) were analyzed. The results showed that the number of differentially accumulated metabolites (DAMs) secreted by T. tortuosa increased with the increase in the Cd concentration, and the biosynthesis of cofactors, D-Amino acid metabolism, Arginine biosynthesis, ATP-binding cassette transporters (ABC transporters), and biosynthesis of alkaloids derived from shikimate pathway were the main pathways enriched by DAMs. The relative abundances of malic acid, N-Formylkynurenine, L-Glutamine, L-Histidine, LL-2,6-Diaminopimelic acid, and fusaric acid in the T2 treatment increased by 16.06%, 62.51%, 14.51%, 11.92%, 21.37%, and 35.79%, respectively (p < 0.05), compared with those of the CK, and the correlation analysis results showed that the above DAMs were closely related to the changes in plant antioxidant enzyme activity and Cd concentration. These results indicate that the secretion of amino acid (N-Formylkynurenine, L-Histidine) and organic acids (isocitric acid, LL-2,6-Diaminopimelic acid, malic acid) through the metabolic pathways, including biosynthesis of amino acids, biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, and ABC transporters, is the metabolic mechanism of T. tortuosa to resist exogenous Cd stress. This study will provide a reference for the monitoring and remediation of heavy metal pollution. Full article

Cardiovascular diseases (CVDs), which include multiple disorders of the heart and blood vessels, are the leading causes of death. Nitric oxide (NO) is a vasodilator that regulates vascular tension. Endogenous NO is produced via the L-arginine–nitric oxide synthase (NOS) pathway. In conditions of cardiovascular dysfunction, NOS activity is impaired, leading to NO deficiency. In turn, the reduction in NO bioactivity exacerbates the pathogenesis of CVDs. Exogenous intake of inorganic nitrate supplements endogenous production via the nitrate–nitrite–NO pathway to maintain the NO supply. Salivary glands play an essential role in the conversion of nitrate to NO, with approximately 25% of circulating nitrate being absorbed and secreted into saliva. As a result, salivary nitrate concentrations can exceed that in the blood by more than tenfold. This recycled nitrate in saliva serves as a reservoir for NO and performs NO-like functions when endogenous NO production is insufficient. In this review, we summarize the emerging benefits of dietary nitrate in CVDs, with a particular focus on salivary-gland-mediated nitrate recirculation in maintaining NO bioavailability and cardiovascular homeostasis. Salivary-gland-mediated nitrate recirculation provides a novel perspective for potential intervention of CVDs. Full article

Black spot, one of the major diseases of kiwifruit, is caused by Alternaria alternata. A comprehensive investigation into its pathogenicity mechanism is imperative in order to propose a targeted and effective control strategy. The effect of L-arginine on the pathogenicity of A. alternata and the underlying mechanisms were investigated. The results showed that treatment with 5 mM L⁻¹ of L-arginine promoted spore germination and increased the colony diameter and lesion diameter of A. alternata in vivo and in vitro, which were 23.1% and 9.3% higher than that of the control, respectively. Exogenous L-arginine treatment also induced endogenous L-arginine and nitric oxide (NO) accumulation by activating nitric oxide synthase (NOS), arginine decarboxylase (ADC) and ornithine decarboxylase (ODC). In addition, exogenous L-arginine triggered an increase in reactive oxygen species (ROS) levels by activating the activity and inducing gene expression upregulation of NADPH oxidase. The hydrogen peroxide (H₂O₂) and superoxide anion (O₂^.−) levels were 15.9% and 2.2 times higher, respectively, than in the control group on the second day of L-arginine treatment. Meanwhile, antioxidant enzyme activities and gene expression levels were enhanced, including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione reductase (GR). In addition, exogenous L-arginine stimulated cell wall-degrading enzymes in vivo and in vitro by activating gene expression. These results suggested that exogenous L-arginine promoted the pathogenicity of A. alternata by inducing the accumulation of polyamines, NO, and ROS, and by activating systems of antioxidants and cell wall-degrading enzymes. The present study not only revealed the mechanism by which low concentrations of L-arginine increase the pathogenicity of A. alternata, but also provided a theoretical basis for the exclusive and precise targeting of A. alternata in kiwifruit. Full article

Background: Cancer is one of the leading causes of death worldwide. The tumor microenvironment makes the tumor difficult to treat, favoring drug resistance and the formation of metastases, resulting in death. Methods: Stimuli-responsive nanoparticles have shown great capacity to be used as a powerful strategy for cancer treatment, diagnostic, as well as theranostic. Nanocarriers are not only able to respond to internal stimuli such as oxidative stress, weakly acidic pH, high temperature, and the high expression of particular enzymes, but also to external stimuli such as light and paramagnetic characteristics to be exploited. Results: In this work, stimulus-responsive nanocarriers functionalized with arginine-glycine-aspartic acid (Arg-Gly-Asp) sequence as well as mimetic sequences with the capability to recognize integrin receptors are analyzed. Conclusions: This review highlights the progress that has been made in the development of new nanocarriers, capable of responding to endogenous and exogenous stimuli essential to combat cancer. Full article

Marine-derived fungi are assuming an increasingly central role in the search for natural leading compounds with unique chemical structures and diverse pharmacological properties. However, some gene clusters are not expressed under laboratory conditions. In this study, we have found that a marine-derived fungus Aspergillus sp. SYPUF29 would survive well by adding an exogenous nitric oxide donor (sodium nitroprusside, SNP) and nitric oxide synthetase inhibitor (L-NG-nitroarginine methyl ester, L-NAME) in culture conditions. Moreover, using the LC-MS/MS, we initially assessed and characterized the difference in metabolites of Aspergillus sp. SYPUF29 with or without an additional source of nitrogen. We have found that the metabolic pathway of Arginine and proline metabolism pathways was highly enriched, which was conducive to the accumulation of alkaloids and nitrogen-containing compounds after adding an additional source of nitrogen in the cultivated condition. Additionally, the in vitro anti-neuroinflammatory study showed that the extracts after SNP and L-NAME were administrated can potently inhibit LPS-induced NO-releasing of BV2 cells with lower IC₅₀ value than without nitric oxide. Further Western blotting assays have demonstrated that the mechanism of these extracts was associated with the TLR4 signaling pathway. Additionally, the chemical investigation was conducted and led to nine compounds (SF1–SF9) from AS1; and six of them belonged to alkaloids and nitrogen-containing compounds (SF1–SF6), of which SF1, SF2, and SF8 exhibited stronger activities than the positive control, and showed potential to develop the inhibitors of neuroinflammation. Full article

This study aimed to evaluate the effects of arginine (0.5%, 1%, 1.5%, 2%, and 2.5% arginine supplementation levels were selected) on the ovarian development of Pacific white shrimp (Litopenaeus vannamei). The analyzed arginine supplementation levels in each diet were 2.90%, 3.58%, 4.08%, 4.53%, 5.04%, and 5.55%, respectively. A total of 540 shrimp (an initial weight of approximately 14 g) with good vitality were randomly distributed into six treatments, each of which had three tanks (300 L in volume filled with 200 L of water), with 30 shrimp per duplicate. Shrimp were fed three times a day (6:00 a.m., 11:00 a.m., and 6:00 p.m.). The results showed that after the 12-week raring cycle, shrimp fed with 4.08% and 4.53% Arg achieved better ovary development, which was identified by ovarian stage statistics, ovarian morphology observation, serum hormone levels (methylfarneside (MF); 5-hydroxytryptamine (5-HT); estradiol (E2); and gonadotropin-releasing hormone (GnRH)), gene expression (DNA meiotic recombinase 1 (dmc1), proliferating cell nuclear antigen (pcna), drosophila steroid hormone 1 (cyp18a), retinoid X receptor (rxra), and ecdysone receptor (ecr)). Further in-depth analysis showed that 4.08% and 4.53% Arg supplementation increased the concentration of vitellogenin in hepatopancreas and serum (p < 0.05) and upregulated the expression level of hepatopancreatic vg and vgr (p < 0.05), which promoted the synthesis of hepatopancreas exogenous vitellogenin and then transported it into the ovary through the vitellogenin receptor and further promoted ovarian maturation in L. vannamei. Meanwhile, compared with the control group, the expression level of vg in the ovary of the 4.53% Arg group was significantly upregulated (p < 0.05), which indicated endogenous vitellogenin synthesis in ovarian maturation in L. vannamei. Moreover, the expression of genes related to the mechanistic target of the rapamycin complex 1 (mTORC1) pathway and protein levels was regulated by dietary arginine supplementation levels. Arginine metabolism-related products, including nitric oxide synthase (NOS), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP), were also affected. RNA interference was applied here to study the molecular regulation mechanism of arginine on ovarian development in L. vannamei. A green fluorescent protein (GFP)-derived double-stranded RNA (dsGFP) is currently commonly used as a control, while TOR-derived dsRNA (dsTOR) and NOS-derived dsRNA (dsNOS) were designed to build the TOR and NOS in vivo knockdown model. The results showed that the mTORC1 and NO-sGC-cGMP pathways were inhibited, while the vitellogenin receptor and vitellogenin gene expression levels were downregulated significantly in the hepatopancreas and ovary. Overall, dietary arginine supplementation could enhance endogenous and exogenous vitellogenin synthesis to promote ovary development in L. vannamei, and the appropriate dosages were 4.08% and 4.53%. The NO-sGC-cGMP and mTORC1 signaling pathways mediated arginine in the regulation of ovary development in L. vannamei. Full article

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism. Full article