Altered Cell Membrane Research Articles

Nanovibrational Stimulation of Escherichia coli Mitigates Surface Adhesion by Altering Cell Membrane Potential.

Mechanical forces shape living matter from the macro- to the microscale as both eukaryotic and prokaryotic cells are force wielders and sensors. However, whereas such forces have been used to control mechanically dependent behaviors in mammalian cells, we lack the same level of understanding in bacteria. Surface adhesion, the initial stages of biofilm formation and surface biofouling, is a mechanically dependent process, which makes it an ideal target for mechano-control. In this study, we employed nanometer surface vibrations to mechanically stimulate bacteria and investigate their effect on adhesion. We discovered that vibrational stimulation at the nanoscale consistently reduces surface adhesion by altering cell membrane potential. Our findings identify a link between bacteria electrophysiology and surface adhesion and provide evidence that the nanometric mechanical "tickling" of bacteria can inhibit surface adhesion.

Fish Oil Supplement Mitigates Muscle Injury In Vivo and In Vitro: A Preliminary Report.

Background: Following injury, older adults exhibit slow recovery of muscle function. Age-related impairment of sarcolemmal membrane repair may contribute to myocyte death, increasing the need for myogenesis and prolonging recovery. Dietary fish oil (FO) is a common nutritional supplement that may alter plasma membrane composition to enhance the response to membrane injury. Methods: We assessed effects of an 8-week dietary intervention on muscle contractile recovery in aged (22 mo.) rats on control (n = 5) or FO (control + 33 g/kg FO (45% eicosapentaenoic acid; 10% docosahexaenoic acid); n = 5) diets 1-week after contusion injury, as well as adult (8 mo., n = 8) rats on the control diet. Results: Recovery was reduced in aged rats on the control diet vs. adults (63 vs. 80%; p = 0.042), while those on the FO diet recovered similarly to (78%) adults. To directly assess sarcolemma injury, C2C12 cells were cultured in media with and without FO (1, 10, and 100 μg/mL; 24 or 48 h) and injured with an infrared laser in medium containing FM4-64 dye as a marker of sarcolemmal injury. FO reduced the area under the FM4-64 fluorescence-time curve at all concentrations after both 24 and 48 h supplementation. Conclusions: These preliminary data suggest FO might aid recovery of muscle function following injury in older adults by enhancing membrane resealing and repair.

Cestrum tomentosum L.f. Extracts against Colletotrichum scovillei by Altering Cell Membrane Permeability and Inducing ROS Accumulation.

Chili pepper anthracnose, caused by Colletotrichum spp., is a significant biotic stress affecting chili fruits globally. While fungicide application is commonly used for disease management due to its efficiency and costeffectiveness, excessive use poses risks to human health and the environment. Botanical fungicides offer advantages such as rapid degradation and low toxicity to mammals, making them increasingly popular for sustainable plant disease control. This study investigated the antifungal properties of Cestrum tomentosum L.f. crude extracts (CTCE) against Colletotrichum scovillei. The results demonstrated that CTCE effectively inhibited conidia germination and germ tube elongation at 40 µg/ml concentrations. Moreover, CTCE exhibited strong antifungal activity against C. scovillei mycelial growth, with an EC50 value of 18.81 µg/ml. In vivo experiments confirmed the protective and curative effects of CTCE on chili pepper fruits infected with C. scovillei. XTT analysis showed that the CTCE could significantly inhibit the cell viability of C. scovillei. Mechanistic studies revealed that CTCE disrupted the plasma membrane integrity of C. scovillei and induced the accumulation of reactive oxygen species in hyphal cells. These findings highlight CTCE as a promising eco-friendly botanical fungicide for managing C. scovillei infections in chili peppers.

Aluminium bioavailability and toxicity disrupted chloroplast structure and inhibited inorganic carbon utilization and nutrient uptake in Vallisneria natans at acidic and alkaline pH

Vallisneria natans, as submerged aquatic plants, face significant threats from aluminium (Al) toxicity. While the effects of Al at low pH on terrestrial plants have been extensively studied, there is a lack of research on the impacts of both low and high pH on chloroplast ultrastructure and nutrient uptake in submerged plants. This research is important as it aims to fill this gap by exposing the leaves of Vallisneria natans to 100 μM Al at varying pH levels (4.5, 5.5, 7.5, and 9.5) for 48 hours. The results showed that inorganic carbon (CT), CO2, and HCO3 content increased at extreme pH levels (4.5 and 9.5), suggesting decreased inorganic carbon utilization under Al stress. Additionally, photosystem II efficiency and electron transport rate were significantly reduced at extreme pH levels, highlighting the sensitivity of V. natans to Al. Chlorophyll a and total chlorophyll content were significantly lower at pH 4.5 compared to pH 7.5. Chloroplast structural disruptions were evident at extreme pH levels coupled with Al exposure, whereas minimal injury was observed at pH 5.5 and 7.5. The study also noted vacuole enlargement, altered plasma membrane permeability, and hematoxylin staining, indicating Al accumulation in leaves. ICP analysis revealed increased Al content at extreme pH levels, underscoring heightened Al bioavailability and toxicity. Significant reductions in macro and micronutrient content (P, Mg, K, Fe, Zn, B, Mn) were observed, likely due to Al-induced root and cell damage and altered nutrient uptake. These findings emphasize the complex interplay between Al exposure, pH fluctuations, and their cascading effects on the physiology and elemental composition of Vallisneria natans, highlighting the need for further research and environmental management strategies.

Combinatorial Effects of Ursodeoxycholic Acid and Antibiotic in Combating Staphylococcus aureus Biofilm: The Roles of ROS and Virulence Factors.

Staphylococcus aureus is a biofilm-forming bacterium responsible for various human infections, one particularly challenging to treat due to its antibiotic resistance. Biofilms can form on both soft tissues and medical devices, leading to persistent and hard-to-treat infections. Combining multiple antimicrobials is a potential approach to overcoming this resistance. This study explored the effects of ursodeoxycholic acid (UDCA) combined with the antibiotic ciprofloxacin against S. aureus biofilms, aiming to evaluate any synergistic effects. Results showed that UDCA and ciprofloxacin co-treatment significantly reduced biofilm formation and disrupted pre-formed biofilms more effectively than either agent alone (p < 0.01). The combination also displayed a slight synergistic effect, with a fractional inhibitory concentration of 0.65. Additionally, the treatment reduced the production of extracellular polymeric substances, increased reactive oxygen species production, decreased metabolic activity, altered cell membrane permeability, and lowered cell surface hydrophobicity in S. aureus. Furthermore, it diminished biofilm-associated pathogenic factors, including proteolytic activity and staphyloxanthin production. Overall, the UDCA-ciprofloxacin combination shows considerable promise as a strategy to combat infections related to staphylococcal biofilms, offering a potential solution to the healthcare challenges posed by antibiotic-resistant S. aureus.

Enhancing phenylethyl alcohol production in Pichia fermentans via adaptive laboratory evolution under NaCl stress

Our previous research demonstrated phenylethyl alcohol was the key aroma in fermented chili peppers, identifying Pichia fermentans as the primary strain responsible for its production. However, the regulatory mechanisms underlying its production remained unclear. To address this, adaptive laboratory evolution against NaCl was utilized in this study to enhance the production of phenethyl and reveal the mechanism of metabolic regulatory of phenethyl alcohol in Pichia fermentans. Under high NaCl stress, the evolved strains increased phenylethyl alcohol production capacity by up to 64.01%. The improved NaCl tolerance of the strains contributes to the higher phenylethyl alcohol yield, primarily because phenylethyl alcohol, like NaCl, causes high osmotic pressure on the strain. The strain responds to NaCl stress by altering cell membrane components and related transport proteins through relevant gene mutations. Additionally, it enhances phenylethyl alcohol production efficiency by upregulating key enzyme-encoding genes (ARO8 and ADHs) in the Ehrlich pathway.

Effect of Synthetic Vitreous Fiber Exposure on TMEM16A Channels in a Xenopus laevis Oocyte Model.

Many years ago, asbestos fibers were banned and replaced by synthetic vitreous fibers because of their carcinogenicity. However, the toxicity of the latter fibers is still under debate, especially when it concerns the early fiber interactions with biological cell membranes. Here, we aimed to investigate the effects of a synthetic vitreous fiber named FAV173 on the Xenopus laevis oocyte membrane, the cell model we have already used to characterize the effect of crocidolite asbestos fiber exposure. Using an electrophysiological approach, we found that, similarly to crocidolite asbestos, FAV173 was able to stimulate a chloride outward current evoked by step membrane depolarizations, that was blocked by the potent and specific TMEM16A channel antagonist Ani9. Exposure to FAV173 fibers also altered the oocyte cell membrane microvilli morphology similarly to crocidolite fibers, most likely as a consequence of the TMEM16A protein interaction with actin. However, FAV173 only partially mimicked the crocidolite fibers effects, even at higher fiber suspension concentrations. As expected, the crocidolite fibers' effect was more similar to that induced by the co-treatment with (Fe3+ + H2O2), since the iron content of asbestos fibers is known to trigger reactive oxygen species (ROS) production. Taken together, our findings suggest that FAV173 may be less harmful that crocidolite but not ineffective in altering cell membrane properties.

Safety of low-intensity extracorporeal shock wave therapy in prostate disorders: in vitro and in vivo evidence.

Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Combination of Cinnamaldehyde/β-cyclodextrin inclusion complex and L-phenylalanine effectively reduces the postharvest green mold in citrus fruit

The essential oil and β-cyclodextrin inclusion complex was able to inhibit the growth of Penicillium digitatum, a damaging pathogen that causes green mold in citrus fruit. In this study, cinnamaldehyde-β-cyclodextrin inclusion complex (β-CDCA) for controlling citrus green mold was synthesized by the co-precipitation method. Characterization of β-CDCA revealed that the aromatic ring skeleton of cinnamaldehyde (CA) was successfully embedded into the cavity of β-CD to form the inclusion complex. β-CDCA inhibited P. digitatum at a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 4.0 g/L. FT-IR spectroscopy analysis, calcofluor white staining, extracellular alkaline phosphatase (AKP) activity and propidium iodide (PI) staining of hyphae morphology showed that β-CDCA may damage the cell ultrastructure and membrane permeability of P. digitatum. The study further demonstrated that hydrogen peroxide (H2O2), malondialdehyde (MDA), and reactive oxygen species (ROS) markedly accumulated in 1/2 MIC β-CDCA treated hyphae. This implied that β-CDCA inhibited growth of P. digitatum by the triggering oxidative stress, which may have caused cell death by altering cell membrane permeability. In addition, in vivo results showed that β-CDCA alone or combined with L-phenylalanine (L-PHe) displayed a comparable level to that of prochloraz. Therefore, β-CDCA combined with L-PHe can thus be used as an eco-friendly preservative for the control green mold in postharvest citrus fruit.

The Role of Alpha Linolenic Acid on Neuroinflammation: A Systemic Review

Neuroinflammation, an inflammatory response within the central nervous system (CNS), plays a critical role in various neurological disorders, including neurodegenerative diseases. Alpha linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid, has shown promising health benefits due to its antioxidant and anti-inflammatory properties. This article aims to thoroughly examine the potential effects of ALA in reducing neuroinflammation, emphasizing its roles as an anti-inflammatory and antioxidant agent. The review focuses on studies published between 2018 and 2023, sourced from reputable academic databases such as PubMed, Semantic Scholar, Google Scholar, and ScienceDirect, with nine key papers selected. The findings indicate that ALA significantly mitigates neuroinflammation by decreasing reactive oxygen species (ROS) via the Nrf-2/HO-1/JNK signaling pathway. Additionally, ALA reduces inflammatory cytokines by inhibiting p-JNK activation, disrupting lipid rafts, blocking the pro-inflammatory transcription factor NF-κB, and altering cell membrane phospholipid composition. The review concludes that ALA may have potential therapeutic effects in reducing neuroinflammation through its antioxidant and anti-inflammatory actions, offering possible benefits for various neurological conditions, including Alzheimer's and Parkinson's diseases.

Effect of surfactant's charge properties on behavior, physiology, and biochemistry and the release of microcystins of Microcystis aeruginosa

Surfactant pollution is escalatitheng in eutrophic waters, but the effect of surfactant charge properties on the physiological and biochemical properties of toxin-producing microalgae remains inadequately explored. To address this gap, this study explores the effects and mechanisms of three common surfactants―cetyltrimethylammonium bromide (CTAB, cationic), sodium dodecyl sulfate (SDS, anionic), and Triton X-100 (nonionic)―found in surface waters, on the agglomeration behavior, physiological indicators, and Microcystin-LR (MC-LR) release of Microcystis aeruginosa (M. aeruginosa) by using UV–visible spectroscope, Malvern Zetasizer, fluorescence spectrometer, etc. Results suggest that charge properties significantly affect cyanobacterial aggregation and cellular metabolism. The CTAB-treated group demonstrates a ∼5.74 and ∼9.74 times higher aggregation effect compared to Triton X-100 and SDS (300 mg/L for 180 min) due to strong electrostatic attraction. Triton X-100 outperforms CTAB and SDS in polysaccharide extraction, attributed to its higher water solubility and lower critical micelle concentration. CTAB stimulates cyanobacteria to secrete proteins, xanthohumic acid, and humic acids to maintain normal physiological cells. Additionally, the results of SEM and ion content showed that CTAB damages the cell membrane, resulting in a ∼90% increase in the release of intracellular MC-LR without cell disintegration. Ionic analyses confirm that all three surfactants alter cell membrane permeability and disrupt ionic metabolic pathways in microalgae. This study highlights the relationship between the surface charge properties of typical surfactants and the dispersion/agglomeration behavior of cyanobacteria. It provides insights into the impact mechanism of exogenous surfactants on toxic algae production in eutrophic water bodies, offering theoretical references for managing surfactant pollution and treating algae blooms.

Enhanced degradation of enrofloxacin in mariculture wastewater based on marine bacteria and microbial carrier

This study aimed to isolate marine bacteria to investigate their stress response, inhibition mechanisms, and degradation processes under high-load conditions of salinity and enrofloxacin (ENR). The results demonstrated that marine bacteria exhibited efficient pollutant removal efficiency even under high ENR stress (up to 10 mg/L), with chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN) and ENR removal efficiencies reaching approximately 88%, 83%, 61%, and 73%, respectively. The predominant families of marine bacteria were Bacillaceae (50.46%), Alcanivoracaceae (32.30%), and Rhodobacteraceae (13.36%). They responded to ENR removal by altering cell membrane properties, stimulating the activity of xenobiotic-metabolizing enzymes and antioxidant systems, and mitigating ENR stress through the secretion of extracellular polymeric substance (EPS). The marine bacteria exhibited robust adaptability to environmental factors and effective detoxification of ENR, simultaneously removing carbon, nitrogen, phosphorus, and antibiotics from the wastewater. The attapulgite carrier enhanced the bacteria's resistance to the environment. When treating actual mariculture wastewater, the removal efficiencies of COD and TN exceeded 80%, TP removal efficiency exceeded 90%, and ENR removal efficiency approached 100%, significantly higher than reported values in similar salinity reactors. Combining the constructed physical and mathematical models of tolerant bacterial, this study will promote the practical implementation of marine bacterial-based biotechnologies in high-loading saline wastewater treatment.

Protease SfpB plays an important role in cell membrane stability and immune system evasion in Streptococcus agalactiae

Bacteria possess the ability to develop diverse and ingenious strategies to outwit the host immune system, and proteases are one of the many weapons employed by bacteria. This study sought to identify S. agalactiae additional serine protease and determine its role in virulence. The S. agalactiae THN0901 genome features one S8 family serine peptidase B (SfpB), acting as a secreted and externally exposed entity. A S8 family serine peptidase mutant strain (ΔsfpB) and complement strain (CΔsfpB) were generated through homologous recombination. Compared to the wild-type strain THN0901, the absorption of EtBr dyes was significantly reduced (P < 0.01) in ΔsfpB, implying an altered cell membrane permeability. In addition, the ΔsfpB strain had a significantly lower survival rate in macrophages (P < 0.01) and a 61.85 % lower adhesion ability to the EPC cells (P < 0.01) compared to THN0901. In the in vivo colonization experiment using tilapia as a model, 210 fish were selected and injected with different bacterial strains at a concentration of 3 × 106 CFU/tail. At 6, 12, 24, 48, 72 and 96 h post-injection, three fish were randomly selected from each group and their brain, liver, spleen, and kidney tissues were isolated. Subsequently, it was demonstrated that the ΔsfpB strain exhibited a markedly diminished capacity for colonization in tilapia. Additionally, the cumulative mortality of ΔsfpB in fish after intraperitoneal injection was reduced by 19.92–23.85 %. In conclusion, the findings in this study have demonstrated that the SfpB plays a significant role in S. agalactiae cell membrane stability and immune evasion. The immune evasion is fundamental for the development and transmission of invasive diseases, the serine protease SfpB may be a promising candidate for the development of antimicrobial agents to reduce the transmission of S. agalactiae.

Altered Plasma Membrane Lipid Composition in Hypertensive Neutrophils Impacts Epithelial Sodium Channel (ENaC) Endocytosis.

Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.

New strain Brevibacillus laterosporus TSA31-5 produces both brevicidine and brevibacillin, exhibiting distinct antibacterial modes of action against Gram-negative and Gram-positive bacteria.

The growing prevalence of antibiotic resistance has made it imperative to search for new antimicrobial compounds derived from natural products. In the present study, Brevibacillus laterosporus TSA31-5, isolated from red clay soil, was chosen as the subject for conducting additional antibacterial investigations. The fractions exhibiting the highest antibacterial activity (30% acetonitrile eluent from solid phase extraction) were purified through RP-HPLC. Notably, two compounds (A and B) displayed the most potent antibacterial activity against both Escherichia coli and Staphylococcus aureus. ESI-MS/MS spectroscopy and NMR analysis confirmed that compound A corresponds to brevicidine and compound B to brevibacillin. Particularly, brevicidine displayed notable antibacterial activity against Gram-negative bacteria, with a minimum inhibitory concentration (MIC) range of 1-8 μg/mL. On the other hand, brevibacillin exhibited robust antimicrobial effectiveness against both Gram-positive bacterial strains (MIC range of 2-4 μg/mL) and Gram-negative bacteria (MIC range of 4-64 μg/mL). Scanning electron microscopy analysis and fluorescence assays uncovered distinctive morphological alterations in bacterial cell membranes induced by brevicidine and brevibacillin. These observations imply distinct mechanisms of antibacterial activity exhibited by the peptides. Brevicidine exhibited no hemolysis or cytotoxicity up to 512 μg/mL, comparable to the negative control. This suggests its promising therapeutic potential in treating infectious diseases. Conversely, brevibacillin demonstrated elevated cytotoxicity in in vitro assays. Nonetheless, owing to its noteworthy antimicrobial activity against pathogenic bacteria, brevibacillin could still be explored as a promising antimicrobial agent.

Design, Synthesis and Antifungal Activity of Nootkatone Derivatives Containing Acylhydrazone and Oxime Ester.

In an attempt to search for new natural products-based antifungal agents, fifty-three nootkatone derivatives were designed, synthesized, and evaluated for their antifungal activity against Phytophthora parasitica var nicotianae, Fusarium oxysporum, Fusarium graminearum and Phomopsis sp. by the mycelium growth rate method. Nootkatone derivatives N17 exhibited good inhibitory activity against Phomopsis. sp. with EC50 values of 2.02 μM. The control effect of N17 against Phomopsis. sp. on kiwifruit showed that N17 exhibited a good curative effect in reducing kiwifruit rot at the concentration of 202 μM(100×EC50 ), with the curative effect of 41.11 %, which was better than commercial control of pyrimethanil at the concentration of 13437 μM(100×EC50 ) with the curative effect of 38.65 %. Phomopsis. sp. mycelium treated with N17 showed irregular surface collapse and shrinkage, and the cell membrane crinkled irregularly, vacuoles expanded significantly, mitochondria contracted, and organelles partially swollen by the SEM and TEM detected. Preliminary pharmacological experiments show that N17 exerted antifungal effects by altering release of cellular contents, and altering cell membrane permeability and integrity. The cytotoxicity test demonstrated that N17 showed almost no toxicity to K562 cells. The presented results implied that N17 may be as a potential antifungal agents for developing more efficient fungicides to control Phomopsis sp.

Integrative chemical and multiomics analyses of tetracycline removal mechanisms in Pseudomonas sp. DX-21

Tetracycline (TC), widely found in various environments, poses significant risks to ecosystems and human health. While efficient biodegradation removes TC, the mechanisms underlying this process have not been elucidated. This study investigated the molecular mechanisms underlying TC biosorption and transfer within the extracellular polymeric substances (EPS) of strain DX-21 and its biodegradation process using fourier transform infrared spectroscopy, molecular docking, and multiomics. Under TC stress, DX-21 increased TC biosorption by secreting more extracellular polysaccharides and proteins, particularly the latter, mitigating toxicity. Moreover, specialized transporter proteins with increased binding capacity facilitated TC movement from the EPS to the cell membrane and within the cell. Transcriptomic and untargeted metabolomic analyses revealed that the presence of TC led to the differential expression of 306 genes and significant alterations in 37 metabolites. Notably, genes related to key enzymes, such as electron transport, peroxidase, and oxidoreductase, exhibited significant differential expression. DX-21 combated and degraded TC by regulating metabolism, altering cell membrane permeability, enhancing oxidative defense, and enhancing energy availability. Furthermore, integrative omics analyses indicated that DX-21 degrades TC via various enzymes, reallocating resources from other biosynthetic pathways. These results advance the understanding of the metabolic responses and regulatory mechanisms of DX-21 in response to TC.

Antibacterial Activities and Underlying Mechanisms of the Compound SYAUP-491 against Xanthomonas oryzae pv. oryzae.

SYAUP-491 is a novel alkyl sulfonamide. In this study, in vivo and in vitro tests were performed along with a proteomic analysis to determine the effects and underlying mechanisms of the antibacterial activity of SYAUP-491 against the causative agent of bacterial leaf blight in rice. The antibacterial test results suggested that SYAUP-491 exhibited significant activities against Xanthomonas oryzae pv. oryzae (Xoo) in vitro and in vivo. The minimal EC50 values reached 6.96 μg/mL and the curative activity reached 74.1%. Detailed studies demonstrated that SYAUP-491 altered membrane permeability and caused morphological changes. Based on proteomics results, SYAUP-491 might inhibit bacterial protein synthesis. SYAUP-491 may disrupt and alter cell membrane permeability and could further act on ribosomes in the bacterial body. Given the above results, SYAUP-491 could serve as a new lead compound in the research of antibacterial control of plant pathogenic bacterial disease.

One-Pot Microfluidics to Engineer Chitosan Nanoparticles Conjugated with Antimicrobial Peptides Using "Photoclick" Chemistry: Validation Using the Gastric Bacterium Helicobacter pylori.

Surface bioconjugation of antimicrobial peptides (AMP) onto nanoparticles (AMP-NP) is a complex, multistep, and time-consuming task. Herein, a microfluidic system for the one-pot production of AMP-NP was developed. Norbornene-modified chitosan was used for NP production (NorChit-NP), and thiolated-AMP was grafted on their surface via thiol-norbornene "photoclick" chemistry over exposure of two parallel UV LEDs. The MSI-78A was the AMP selected due to its high activity against a high priority (level 2) antibiotic-resistant gastric pathogen: Helicobacter pylori (H. pylori). AMP-NP (113 ± 43 nm; zeta potential 14.3 ± 7 mV) were stable in gastric settings without a cross-linker (up to 5 days in pH 1.2) and bactericidal against two highly pathogenic H. pylori strains (1011 NP/mL with 96 μg/mL MSI-78A). Eradication was faster for H. pylori 26695 (30 min) than for H. pylori J99 (24 h), which was explained by the lower minimum bactericidal concentration of soluble MSI-78A for H. pylori 26695 (32 μg/mL) than for H. pylori J99 (128 μg/mL). AMP-NP was bactericidal by inducing H. pylori cell membrane alterations, intracellular reorganization, generation of extracellular vesicles, and leakage of cytoplasmic contents (transmission electron microscopy). Moreover, NP were not cytotoxic against two gastric cell lines (AGS and MKN74, ATCC) at bactericidal concentrations. Overall, the designed microfluidic setup is a greener, simpler, and faster approach than the conventional methods to obtain AMP-NP. This technology can be further explored for the bioconjugation of other thiolated-compounds.

ACSL4-Mediated Membrane Phospholipid Remodeling Induces Integrin β1 Activation to Facilitate Triple-Negative Breast Cancer Metastasis.

ACSL4 upregulation in triple-negative breast cancer alters cell membrane phospholipid composition to increase integrin β1 activation and drive metastasis, indicating that targeting ACSL4 could potentially block metastasis and improve patient outcomes.