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Biology subjects

Mehta, D.

Publications and source records attributed to Mehta, D..

At least 19 recordsLinked to original sources

Quantitative proteomics uncovers a role for REVEILLE8- like clock genes in osmotic and salt stress response in Arabidopsis

The plant circadian clock governs the precise regulation of plant developmental and environmental responses within a 24 h photoperiod. Consisting of a series of interconnected transcription factor moderated feedback loops, each operating at specific times of day within the photoperiod, more than 30% of Arabidopsis genes show circadian regulation. REVEILLE (RVE) genes exhibit highest expression in the afternoon, and act as activators of afternoon-expressed clock genes, including TOC1 and PRR5. Specifically, RVE4, 6 and 8 have been identified as regulators of both plant growth and development, along with temperature responses. Previous work using Arabidopsis has implicated soybean RVE8-like proteins in drought responses, however, there remains a lack of understanding of how these RVEs control abiotic stress responses, particularly relating to proteome-level regulation. Here, using quantitative proteomics, we resolve how the rve4 6 8 proteome responds to osmotic and salt stress at end-of-day and end-of-night timepoints. Our results indicate that rve4 6 8 plants have substantially altered regulation of proteins related to osmotic stress, photosynthesis and phenylpropanoid metabolism, particularly at end-of-day. Further, we resolve new drought-responsive targets impacted by the loss of RVE4, 6, and 8 that are involved in vesicle transport, fatty acid metabolism and abscission. Overall, our data provide a new resource for understanding how RVE8-like proteins impact plant drought-like responses, offering opportunities for future chronoculture-informed breeding of climate-resilient crops.

Plant Biology↗

PathPinpointR: Predicting the progression of sc-RNAseq samples through reference trajectories.

Single-cell RNA sequencing (scRNA-seq) has transformed our ability to analyse cellular heterogeneity, enabling detailed mapping of cellular progression. Trajectory inference tools construct trajectories from scRNA-seq data, facilitating the tracing of cellular progression through developmental pathways. PathPinpointR (PPR) is a lightweight and user-friendly R package developed to predict and compare the positions of scRNA-seq samples along reference biological trajectories, such as those created from large cell atlas projects. PPR utilises sets of switching-gene events from reference trajectories as indicators of cellular progression. By applying these positional indicators to query datasets, each cell can be accurately assigned a pseudo-time value, providing predictive insight into its position along a trajectory. This information can be used to stage cells within an established developmental process, or to evaluate how different patient samples compare when mapped onto reference disease or drug response trajectories. AvailabilityPathPinpointR is available at https://github.com/moi-taiga/PathPinpointR. Contacto.j.l.rackham@soton.ac.uk

bioinformatics↗

Withania somnifera root extract reduces susceptibility of the model worm Caenorhabditis elegans to different types of stressors

BackgroundWithania somnifera, commonly known as Ashwagandha, is one of the most widely prescribed plants in the Indian system of traditional medicine. Its roots are believed to impart comprehensive health benefits supporting lifespan and healthspan through its anti-stress, immunomodulatory, and neuroprotective activity. Scientific validation of its claimed biological effects is warranted. MethodsThe nematode worm Caenorhabditis elegans was challenged with heat or certain neurotoxic/mitotoxic chemical stressors, and worm activity (healthspan) was compared between W. somnifera root extract (WSRE)-exposed and control worm populations, through an automated worm tracker. ResultsPrevious exposure of worms to WSRE conferred prophylactic benefit on them in face of subsequent challenge with rotenone, MnCl2, or levamisole. Worms pre-exposed to either of these toxins were able to recover faster in presence of WSRE. This extract was also able to reduce the susceptibility of wild type worms to heat-induced paralysis, and that of transgenic worms to beta-amyloid mediated paralysis. ConclusionsAdaptogenic potential of W. somnifera roots was demonstrated in worm model. WSRE can be said to possess a wide anti-stress spectrum as it protected the worms against different stressors inducing toxicity through different mechanisms including interference with acetylcholine and dopamine neurons and function. Our results support the candidature of W. somnifera roots as a potent nutraceutical.

pharmacology and toxicology↗

The plant circadian clock exerts stronger control over the diel proteome than the transcriptome

AbstractThe plant circadian clock is a genetic circuit composed of multiple mutually-regulating transcription factors that together synchronize internal biological rhythms to the [~]24-hour period of planetary rotation. While it has been known for over a decade that nearly 40% of the transcriptome in the model plant Arabidopsis oscillates with a circadian rhythm, it is yet unclear to what extent this translates to the proteome. Here, through parallel quantitative proteome and transcriptome time-course profiling of Arabidopsis wild-type plants and a panel of clock deficient plant lines, we show that specific clock genes exercise extensive control over diel proteome rhythmicity, and to a much greater extent than they do the transcriptome. This control results in a clock-dependent synchronization of rhythmic proteins along a bimodal phase distribution that is lost in circadian clock deficient plants. This suggests pervasive post-translational control of gene expression by specific elements of the circadian system, notably the morning expressed LHY/CCA1 module. Our findings imply that the circadian clock exercises much greater control of gene expression through proteostasis mechanisms than previously recognised, necessitating a recalibration of our current understanding of clock proteins as primarily transcriptional regulators.

plant biology↗

Nanodomain formation in lipid bilayers I: Quantifying the nanoscopic miscibility transition with FRET

We present a robust and easy-to-use methodology for determining the nanoscopic miscibility transition temperature, nm-Tmix, of lipid bilayer mixtures from FRET measurements. The method relies on the use of freely diffusing fluorescent donor and acceptor lipids that partition non-uniformly between coexisting phases. When this condition is met, changes in lipid clustering that occur as the sample passes through the transition result in abrupt changes in the spatial distribution of probes and consequently, abrupt changes in the FRET signal. FRET vs. temperature data can then be modeled with a phenomenological piecewise function that describes how the signal changes above and below nm-Tmix. Using lattice simulations, we show that the transition between these regimes occurs when the size of lipid clusters surpasses a critical threshold that is approximately equal to twice the Forster distance of the donor/acceptor pair, or about 10 nm. Because other, temperature-dependent factors unrelated to lateral organization--such as changes in lipid molecular area and donor photophysics--can also influence the FRET signal, we also fit the data using a simpler model of uniform mixing. An information theory-based test comparing the fit quality of the uniform and phase separated models provides a straightforward and robust criterion for objectively assessing whether a given sample undergoes a nanoscopic miscibility transition within a temperature range of interest. We highlight the distinction between nm-Tmix determined by FRET (or methods with comparable spatial resolution) and the micron-scale transition temperature, m-Tmix, determined from diffraction-limited optical techniques. The analysis software is freely available from an online repository.

biophysics↗

Nanodomain formation in lipid bilayers II: The influence of mixed-chain saturated lipids

An important class of lipids found in biological membranes are composed of two structurally different hydrocarbon chains. Among these, low-melting lipids possessing both a saturated and unsaturated chain have been intensely studied because of their biological abundance and influence on lipid rafts. In contrast, much less is known about the biophysical effects of mixed chains in high-melting lipids. Here, we investigated two such lipids--MSPC (14:0-18:0 PC) and SMPC (18:0-14:0 PC)--to determine how chain length mismatch and acyl chain position on the glycerol backbone influence lateral organization. We studied the temperature-and composition-dependent phase behavior of liposomes composed of either mixed-chain or symmetric-chain high-melting lipids plus DOPC and cholesterol, using techniques sensitive to domain formation at both microscopic and nanoscopic length scales. All studied mixtures exhibited liquid-ordered (Lo) + liquid-disordered (Ld) phase coexistence with domains that were visible in confocal microscopy experiments. FRET measurements showed that all mixtures also exhibited nanoscopic heterogeneity at temperatures above the microscopic miscibility transition temperature, and cryo-EM imaging further revealed bilayer thickness variation consistent with coexisting Ld and Lo phases. Both the microscopic miscibility transition temperature, m-Tmix, and its nanoscopic counterpart, nm-Tmix, were strongly correlated with the melting transition temperature of the saturated lipid; the sole exception was SMPC/DOPC/Chol, whose m-Tmix showed a significant negative deviation from the expected value, implying an enhanced propensity for nanoscopic phase separation in mixtures containing this high-melting species. These results point to strong effects of acyl chain position within mixed-chain high-TM lipids on the microscopic phase behavior of ternary mixtures.

biophysics↗

Engineered RVG29-Conjugated Chitosan for Enhanced Brain Delivery of Kisspeptin Agonists and Antagonists in Reproductive Health.

Efficient delivery of intact therapeutic peptides across the blood-brain barrier (BBB) remains a central obstacle in translating neuroendocrine modulators to clinical practice. Kisspeptin receptor (KISS1R) agonists and antagonists precisely regulate gonadotropin-releasing hormone (GnRH) pulsatility, thereby controlling luteinizing hormone (LH) release, steroidogenesis, and fertility. While the KISS1R agonist KP10 accelerates GnRH-LH pulses to promote ovulation, the antagonist KP234 suppresses pulse generation, inducing reversible infertility. However, their poor BBB permeability limits clinical application. Here, we engineered a non-invasive brain delivery platform by covalently coupling the rabies virus glycoprotein-derived peptide RVG29 to oxidized chitosan nanoparticles via Schiff base chemistry. Sodium periodate oxidation introduced aldehyde groups, FT-IR confirmed aldehyde formation, and UV-Vis spectroscopy validated RVG29 conjugation through characteristic absorbance shifts. The resulting RVG29 - chitosan carriers demonstrated biocompatibility, enhanced neuronal uptake [~]2.1-fold in vitro, and achieved [~]2.5-fold higher brain accumulation in vivo compared to unconjugated controls. Systemic delivery of RVG29-chitosan-KP10 restored and amplified LH pulsatility in ovariectomized mice, accelerated estrous cycling, increased preovulatory follicle numbers, and enhanced litter size. In contrast, RVG29-chitosan-KP234 abolished LH pulses, maintained animals in persistent diestrus, depleted corpora lutea, and produced complete yet reversible infertility. Longitudinal dosing demonstrated stable neuroendocrine modulation without systemic toxicity, and ovarian histology confirmed ovulatory arrest in antagonist-treated animals. By enabling programmable, bidirectional control of a central hypothalamic circuit through systemic delivery of unmodified peptides, this platform addresses a long-standing barrier in neuroendocrine therapeutics. Beyond fertility regulation, this approach can be adapted to other hypothalamic-driven processes, including metabolic, stress-axis, and circadian control.

bioengineering↗

Genome-wide identification of conserved RNA structure in plastids

Plastid genomes are deeply evolutionary conserved. RNA structures within the primary or mature transcript play central role in plastid regulation of RNA processing, stability, and translation. However, the identity and conservation of RNA structures selected in plastid's evolution are still largely elusive. Here, we developed a stringent, covariation-based pipeline that perform an unbiased screen for conserved RNA secondary structures across entire plastid genomes. We analysed ~14,000 plastid genomes and identified a repertoire of 57 high-confidence conserved structures. We recovered known functional classes, e.g., 16S rRNA, tRNA, group II intron, and 3' end stem-loop, evidencing that our genome-wide analysis is reliable. We further uncovered novel putative cis-acting structures within the UTRs and introns of key photosynthetic genes, including psbN, clpP, and atpF, as well as putative trans-acting antisense RNAs to petB and psbT, suggesting uncharacterized elements with major regulatory function. Experimental in vivo RNA probing demonstrated that nearly half of the conserved structures adopt the predicted conformation in Arabidopsis plastid. Our comprehensive, yet stringent atlas of conserved plastid RNA structures provides the foundations for new regulatory discoveries in plastid biology.

plant biology↗

Phosphate resupply differentially impacts the shoot and root proteomes of Arabidopsis thaliana seedlings

Phosphate (Pi) is an essential macronutrient for plant development that is often limited in soil environments. Plants have evolved myriad dynamic biochemical, physiological, and morphological adaptations to cope with nutritional Pi deficiency, collectively known as the Pi starvation response (PSR). While many components of the PSR have been well-characterized, much less is known about how metabolic homeostasis is re-established upon Pi resupply, particularly with respect to tissue- and time-specific adaptations. Here, we applied label-free quantitative proteomics to quantify protein-level changes in Arabidopsis thaliana shoots and roots following Pi resupply after prolonged Pi deprivation, quantifying a total of [~]2,700 differentially abundant proteins (DAPs). Sampling at early (1 h) and late (48 h) time-points, we captured a combination of immediate signaling and metabolic responses, along with longer-term recovery processes. Early responses prioritized metabolic adjustments to restore Pi pools via enhanced glycolysis and energy production, followed by later shifts toward anabolism, including nucleotide production, membrane remodeling, and protein synthesis. Several key enzymes, including ALTERNATIVE OXIDASE 1A, FRUCTOSE- BISPHOSPHATE ALDOLASE 5, and subunits of PHOTOSYSTEM I exhibited unique tissue-specific and time-dependent regulation. Overall, our findings reveal dynamic temporal phases of metabolic reprogramming during recovery from Pi starvation, and identify candidate proteins involved in orchestrating this transition, ultimately identifying potential targets for enhancing Pi uptake- and use-efficiency in crops. While hydroponic liquid culture enabled precise control of Pi availability, soil responses may be further influenced by heterogeneity and other root interactions.

plant biology↗

An inducible tethered function assay reveals differential regulatory effects for the RNA-binding protein YBX3 and its domains.

RNA-binding protein (RBP) regulation is widespread across biology from development to learning and memory. Often RBPs contain multiple modular domains, which contribute to distinct RNA- binding activity or interactions necessary for regulation. However, assays to determine specific regulatory activity of individual domains are limited. The tethered function assay (TFA) provides a direct method to assess the functional activity of RBPs and their domains. The assay consists of two key components: (i) a reporter plasmid that encodes an mRNA, such as luciferase or GFP, engineered with high-affinity binding sites for an exogenous RNA-binding factor, and (ii) an effector construct that expresses a chimera of the RBP fused to the RNA-binding factor. Co- transfection of these constructs allows for measurement of reporter activity as a quantitative readout for RBP regulatory function. We developed an inducible TFA (iTFA) system through generation of a stable inducible mammalian cell line to express a reporter mRNA encoding nanoluciferase (nLuc) with six high-affinity MS2 binding sites within its 3 untranslated region. These cells can be transfected with a single plasmid that expresses an RBP fused to the MS2 coat protein. This approach enhances efficiency and reproducibility through reduction of transfection burden to a single plasmid and simplified normalization. We used this platform to dissect the individual and combined regulatory effects of YBX3 domains, a modular RBP with differential regulatory activity. The iTFA system provides a streamlined, tunable platform for functional analysis of RBPs that facilitates rapid interrogation of RBP or domain-specific activities in mammalian cells.

molecular biology↗

A Single Mutation in TRPC6 Protects Mice from Acute Lung Injury by Regenerating Endothelium

Regenerating vascular endothelium under sepsis, trauma, and viral infections is vital for promoting the resolution of inflammatory diseases such as acute lung injury (ALI). Transient receptor potential canonical (TRPC) channels mediated Ca2+ entry compromises organ functions and survival from lung injury. Through decoding the domain in TRPC6 responsible for vascular injury, we unveiled the intricate molecular mechanisms underlying vascular regeneration in injured tissue. We found that the substitution of isoleucine111 within the Ist ankyrin domain of TRPC6 for its isomer 111leucine (I111L-TRPC6) altered channel localization at the membrane, blocked TRPC6-mediated Ca2+ entry and cation currents without affecting TRPC6 protein expression. Next, we delivered WT-TRPC6 and I111L-TRPC6 to the endothelial cells (ECs) of TRPC6 knockout mice using liposomes and found that while WT-TRPC6 induced lung vascular inflammatory injury and EC death these responses were blocked in lungs expressing I111L-TRPC6 mutant. Instead, the I111L-TRPC6 mutant promoted lung EC proliferation and prevented vascular injury. These responses were recapitulated in a preclinical mouse model of ALI after injection of engineered TRPC6-blocking peptide, suggesting a novel strategy for regenerating anti-inflammatory vascular niche and preventing ALI therapeutically.

cell biology↗

Halogenated cholesterol alters the phase behavior of ternary lipid membranes

Eukaryotic plasma membranes exhibit nanoscale lateral lipid heterogeneity, a feature that is thought to be central to their function. Studying these heterogeneities is challenging since few biophysical methods are capable of detecting domains at sub-micron length scales. We recently showed that cryogenic electron microscopy (cryo-EM) can directly image nanoscale liquid-liquid phase separation in extruded liposomes due to its ability to resolve the intrinsic thickness and electron density differences of ordered and disordered phases. However, the intensity contrast between these phases is poor compared to conventional fluorescence microscopy and is thus both a limiting factor and a focal point for optimization. Because the fundamental source of intensity contrast is the spatial variation in electron density within the bilayer, lipid modifications aimed at selectively increasing the electron density of one phase might enhance the ability to resolve coexisting phases. To this end, we investigated model membrane mixtures of DPPC/DOPC/cholesterol in which one hydrogen of cholesterols C19 methyl group was replaced by an electron-rich halogen atom (either bromine or iodine). We characterized the phase behavior as a function of composition and temperature using fluorescence microscopy, FRET, and cryo-EM. Our data suggest that halogenated cholesterol variants distribute approximately evenly between liquid-ordered and liquid-disordered phases and are thus ineffective at enhancing the intensity difference between them. Furthermore, replacing more than half of the native cholesterol with halogenated cholesterol variants dramatically reduces the size of membrane domains. Our results reinforce how small changes in sterol structure can have a large impact on the lateral organization of membrane lipids.

biophysics↗

Quantitative proteomic analysis of soil-grown Brassica napus responses to nutrient deficiency

ABSTRACTMacronutrients such as nitrogen (N), phosphorus (P), potassium (K), and sulphur (S) are critical for plant growth and development. Field-grown canola (Brassica napus L.) is supplemented with fertilizers to maximize plant productivity, while deficiency in these nutrients can cause significant yield loss. A holistic understanding of the interplay between these nutrient deficiency responses in a single study and canola cultivar is thus far lacking, hindering efforts to increase the nutrient use efficiency of this important oil seed crop. To address this, we performed a comparative quantitative proteomic analysis of both shoot and root tissue harvested from soil-grown canola plants experiencing either nitrogen, phosphorus, potassium, or sulphur deficiency. Our data provide critically needed insights into the shared and distinct molecular responses to macronutrient deficiencies in canola. Importantly, we find more conserved responses to the four different nutrient deficiencies in canola roots, with more distinct proteome changes in aboveground tissue. Our results establish a foundation for a more comprehensive understanding of the shared and distinct nutrient deficiency response mechanisms of canola plants and pave the way for future breeding efforts.

plant biology↗

Withania somnifera root extract (LongeFera-TM) confers beneficial effects on health and lifespan of the model worm Caenorhabditis elegans

Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans. Extract-exposed worms registered longer lifespan, higher fertility, better motility and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt- 1, dpy-4, dpy-13, and col-17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy-13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through cooccurrence analysis to have their homologous counterpart in humans. Our results validate the potential of W. somnifera extract as a phytopharmaceutical.

molecular biology↗

Importin alpha inhibitors act against the differentiated stages of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii

Protozoan parasites of the phylum Apicomplexa, including Plasmodium falciparum and Toxoplasma gondii, cause widespread disease in humans. New drugs and protein targets are required for the treatment of these diseases, particularly therapies targeting multiple stages of the parasite life cycles. Nuclear import, carried out by the transporters importin (IMP) and {beta} subunits, is a valid target for the discovery of lead compounds against these protozoan parasites: small molecules were identified that inhibit interactions between IMP and nuclear localisation signals in vitro and also inhibit the growth of the rapidly-dividing stages of P. falciparum and T. gondii (asexual stages and tachyzoites) in culture. In this report, we add another small molecule (Bay 11-7082) to the panel of inhibitors of IMP and test the ability of these inhibitors to first, inhibit nuclear transport in the rapidly dividing stages and, next, the maturation of differentiated stages of both parasites. We show that GW5074 and CAPE inhibit nuclear transport in the P. falciparum blood stages, while Bay 11-7085 inhibits nuclear transport in T. gondii tachyzoites. Interestingly, CAPE strongly inhibits gametocyte maturation, the sexual stages of P. falciparum, and Bay 11-7085 weakly inhibits bradyzoite differentiation, the latent stages of T. gondii. As differentiation of both these stages is dependent on activation of gene expression, triggered by the nuclear translocation of transcription factors, our work provides a "proof of concept" that targeting nuclear import is a viable strategy for the development of therapeutics against multiple stages of apicomplexan parasites, some of them recalcitrant to existing drugs.

molecular biology↗

B4 Raf-like MAPKKK RAF24 regulates Arabidopsis thaliana flowering time through HISTONE MONO-UBIQUITINATION 2

The timing of flowering is a critical agronomic trait governed by a number of external cues. Despite our genetic understanding of flowering time being well established, we have a limited understanding of how these signals are transmitted to different flowering genes through protein phosphorylation. Here, we characterize a novel B4 Raf-like MAPKKK protein kinase called RAF24, whose mutation results in an early flowering phenotype. Comparative analysis to related B4 Raf-like MAPKKKs indicates that RAF24 uniquely affects flowering time, while phosphoproteome analyses found RAF24 impacts the phosphorylation status of proteins involved in distinct flowering pathways. In particular, we found the RING-type ubiquitin ligase HISTONE MONO-UBIQUITINATION 2 (HUB2) to possess the largest phosphorylation change in raf24 deficient plants relative to wild-type Arabidopsis and that RAF24 suppresses ligase activity of HUB2 in order to maintain appropriate levels of H2Bub1. Furthermore, we found that RAF24 regulates HUB2 phosphorylation through subclass I and III SUCROSE NON-FERMENTING KINASE 2 (SnRK2) protein kinases; known substrates of B4 RAF-like MAPKKKs. Lastly, using a combination of phospho-mimetic and -ablative plant lines, we validate the importance of HUB2 phosphorylation at S314 in regulating flowering time. Collectively, our findings implicate RAF24 as a higher-order flowering regulator, while further implicating HUB2 as a centerpiece of flowering regulation.

plant biology↗

Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients. We show that ERG loss in ECs rewired PMN-transcriptome, enriched for genes associated with the CXCR2-CXCR4 signaling. Rewired PMNs compromise mice survival after pneumonia and induced lung vascular inflammatory injury following adoptive transfer into naive mice, indicating their longevity and inflammatory activity memory. Mechanistically, EC-ERG restricted PMN extravasation and activation by upregulating the deubiquitinase A20 and downregulating the NF{kappa}B-IL8 cascade. Rescuing A20 in EC-Erg-/- endothelium or suppressing PMN-CXCR2 signaling rescued EC control of PMN activation. Findings deepen our understanding of EC control of PMN-mediated inflammation, offering potential avenues for targeting various inflammatory diseases. HighlightsO_LIERG regulates trans-endothelial neutrophil (PMN) extravasation, retention, and activation C_LIO_LILoss of endothelial (EC) ERG rewires PMN-transcriptome C_LIO_LIAdopted transfer of rewired PMNs causes inflammation in a naive mouse C_LIO_LIERG transcribes A20 and suppresses CXCR2 function to inactivate PMNs C_LI In brief/blurbThe authors investigated how vascular endothelial cells (EC) control polymorphonuclear neutrophil (PMN) extravasation, retention, and activation to strengthen tissue homeostasis. They showed that EC-ERG controls PMN transcriptome into an anti-adhesive and anti-inflammatory lineage by synthesizing A20 and suppressing PMNs-CXCR2 signaling, defining EC-ERG as a target for preventing neutrophilic inflammatory injury.

immunology↗

Silversol (a colloidal nanosilver formulation) inhibits growth of antibiotic-resistant Staphylococcus aureus by disrupting its physiology in multiple ways

Antibacterial effect of a colloidal nanosilver formulation Silversol(R) was investigated against an antibiotic-resistant strain of Staphylococcus aureus. Lower concentrations of the test formulation exerted bacteriostatic and, its higher concentrations exerted bactericidal effect against this pathogen. Silversol(R) at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed the genes coding for transcriptional regulators, efflux machinery, transferases, {beta}-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis to get expressed differently under influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol(R) in S. aureus.

microbiology↗