Biology subjects

Santiago, M.

Publications and source records attributed to Santiago, M..

13 recordsLinked to original sources

bioRxiv2026

(+)-trans-Cannabidiol is a CB2 receptor agonist

3:(-)-trans-Cannabidiol ((-)-CBD) is a principal phytocannabinoid from Cannabis sativa. (-)-CBD has complex pharmacology but is a relatively weak inhibitor of CB1 and CB2 receptor signalling. Cannabidiol has two chiral centres and thus four stereoisomers. (+)-trans-CBD ((+)-CBD) has a higher affinity than (-)-CBD at CB1 and CB2, but its pharmacodynamic effects at these receptors are incompletely described. We examined the activity of (+)-CBD at human CB1 and CB2 receptors using a fluorescence-based assay of membrane potential in AtT20 cells stably expressing CB1 or CB2 receptors. (+)-CBD produced a rapid, concentration-dependent hyperpolarization in CB2-expressing cells (pEC50 6.63 {+/-} 0.08) with a maximal effect [~]90% of the response to CP55940. The CB2 response was blocked by pertussis toxin pretreatment and competitively inhibited by the CB2 antagonist AM630 (Schild slope 1.1 {+/-} 0.1). (+)-CBD was a low-efficacy, low-potency CB1 agonist and inhibited somatostatin-receptor effects at high concentrations (10-30 {micro}M). It had no effect on the membrane potential of AtT20 wild-type cells. In silico modelling of ligand interactions with CB2 indicated that (+)-CBD but not (-)-CBD formed an H-bond with Ser285, a residue crucial for agonist activation of CB2. Our data suggests (+)-CBD acted as a CB2 agonist via the orthosteric binding site on the receptor. Synthetic CBD, including (+)-CBD, has previously been administered in clinical trials, presumably without consideration of its potential CB2 agonist activity. Given the relative safety of (-)-CBD in people, (+)-CBD may be a useful drug to explore CB2-sensitive disease states, should it prove similarly safe.

pharmacology and toxicology↗

bioRxiv2026

Tetracycline-Regulated Inducible CB2 Expression in AtT20 Cells: A Functional Assay for Quantifying Ligand Efficacy

IntroductionCannabinoid receptor-2 (CB2) is an emerging therapeutic target for chronic and inflammatory pain, cancer, and neurological disorders. Understanding the efficacy of CB2 ligands is crucial for future drug design and development. AimsWe aimed to establish a simple and robust system to control CB2 expression using a tetracycline-regulated mammalian expression system (T-REx), to enable application of the Black and Leff operational model to measure the operational efficacy ({tau}) of CB2 ligands. MethodsLigand-induced hyperpolarisation of AtT20 cells transfected with T-REx and human CB2 was measured by FLIPR membrane potential assay. Maximal and submaximal responses of the CB2 ligands were produced by regulating CB2 expression using tetracycline. Data were fitted to the operational model of receptor depletion to quantify the efficacy of seven ligands. Additionally, the maximal initial rate of signalling (IRmax), another putative measure of ligand efficacy, was determined. ResultsAK-F-064, CP55940 and 2-AG exhibited similar efficacy with a {tau} values of 11.4, 11 and 10.4 respectively, while anandamide (AEA) had the lowest efficacy ({tau}=1.07) among the tested agonists. The rank order of operational efficacy and IRmax was similar and was estimated as: AK-F-064 = CP55940 = 2-AG > 5F-AB-PICA = WIN55212-2 > HU-308 = AEA. ConclusionThis inducible expression system provides a reliable platform for quantifying and comparing CB2 ligand efficacy using the operational model. This approach may facilitate more precise CB2-targeted drug development and can be readily extended to other GPCR targets.

pharmacology and toxicology↗

bioRxiv2025

Dietary α-Ketoglutarate delays lung adenocarcinoma in females and modulates TBX5-associated transcriptional programs and the immune microenvironment

Lung adenocarcinoma (LUAD) is the most common form of lung cancer and a leading cause of cancer-related mortality, underscoring the need for new chemopreventive strategies. -Ketoglutarate (-KG), a tricarboxylic acid cycle metabolite and dioxygenase cofactor, links cellular metabolism to chromatin regulation. Here, we show that dietary -KG remodels LUAD in a sex-dependent manner. In female mice, -KG reduced tumor area, decreased repressive histone marks (H3K27me3, H3K9me3), and upregulated TBX5 and myogenesis-associated genes. In male mice, -KG-treated male mice exhibited increased tumor area, elevated H3K27me3, and immune remodeling characterized by CD8 T cell expansion and transcriptomic signatures of T cell exhaustion. Analysis of human LUAD revealed that TBX5 expression is enriched in female tumors and associated with improved survival, suggesting it may serve as a marker of favorable outcome. Together, these findings support -KG as an epigenetic modulator with potential chemopreventive activity in lung cancer and highlight the importance of incorporating sex as a biological variable in preclinical studies. SummaryOral -Ketoglutarate (-KG) has a known anti-aging effect and has been suggested to inhibit cancer development. However, the role of -KG in lung cancer is not known. Here, we investigated the effect of oral -KG on the development of lung adenocarcinoma in a KrasG12D-driven murine model. In females, -KG reduced lung tumor growth, accompanied by TBX5 induction, activation of a myogenesis transcriptional program, and loss of repressive histone methylation. In males, -KG increased tumor growth, coinciding with TBX5 repression, suppression of myogenesis programs, and accumulation of repressive histone methylation. -Ketoglutarate also remodeled the tumor immune microenvironment in a sex-dependent manner, with divergent effects on T cell infiltration. HIGHLIGHTSO_LIOral -Ketoglutarate reduces lung adenocarcinoma development in a genetically engineered murine model in a sex-dependent manner C_LIO_LIIn females, -Ketoglutarate reduces repressive histone marks and induces TBX5/myogenesis C_LIO_LIIn males, -Ketoglutarate increases repressive histone marks and suppresses TBX5/myogenesis C_LIO_LI-Ketoglutarate remodels the tumor immune microenvironment with sex-specific effects C_LIO_LITBX5 is enriched in female LUAD patients and predicts improved survival in human datasets C_LI CONTEXT AND SIGNIFICANCELung adenocarcinoma (LUAD) is the most common form of lung cancer and a leading cause of cancer mortality worldwide. Preventive strategies are limited, highlighting the need for safe approaches that can intercept tumor progression. Metabolic cofactors are increasingly recognized as modulators of the cancer epigenome. Among these, -Ketoglutarate (-KG), a central metabolite of the tricarboxylic acid cycle, functions as a cofactor for chromatin-modifying enzymes. Here, we demonstrate that dietary -KG supplementation limits LUAD progression in female mice, reduces repressive histone methylation, and activates TBX5-associated transcriptional programs. These effects are sex dependent, underscoring the importance of biological context in shaping metabolic responses. In human LUAD, TBX5 is enriched in females and predicts improved survival, suggesting that it may serve as a marker of favorable outcome and help guide future studies of -KG. Together, this work identifies -KG as an epigenetically active metabolite with translational promise for lung cancer chemoprevention. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/677388v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1615a31org.highwire.dtl.DTLVardef@68884corg.highwire.dtl.DTLVardef@cc5ed1org.highwire.dtl.DTLVardef@1652c60_HPS_FORMAT_FIGEXP M_FIG C_FIG One-sentence summary-Ketoglutarate remodels lung adenocarcinoma through sex-dependent epigenetic, transcriptional, and immune reprogramming.

cancer biology↗

bioRxiv2024

Polyunsaturated fatty acids and their endocannabinoid-related metabolites activity at human TRPV1 and TRPA1 ion channels expressed in HEK-293 cells.

BackgroundPolyunsaturated fatty acids (PUFAs), particularly Omega-3 ({omega}-3) and Omega-6 ({omega}-6) PUFAs, may exert neuroprotective effects via the endocannabinoid system (ECS) and are promoted as brain health supplements. However, despite their potential role in endocannabinoid biosynthesis, the impact of PUFAs on ion channels such as TRPV1 and TRPA1, which are modulated by endocannabinoids, remains incompletely understood. Furthermore, the potential in vitro actions of {omega}-6 to {omega}-3 PUFA combined in the ratios available in supplements remains uncertain. Therefore, the objective of this study is to evaluate the functional activity of individual PUFAs, their combination in a specific ratio, and their endocannabinoid-related derivatives on TRPV1 and TRPA1 ion channels. MethodologyWe employed a fluorescent Ca-sensitive dye in HEK-293 Flp-In T-REx cells expressing human TRPV1, TRPA1, or an empty vector to measure changes in intracellular calcium concentration ([Ca2+]i). ResultsCapsaicin and certain PUFA derivatives such as DHEA, {gamma}-LEA and AEA stimulate TRPV1 activity directly, whereas EPA, DHA, {gamma}-LA, and their 9:3:1 ratio triggered TRPV1 response via a mechanism dependent on prior exposure to phorbol ester. Similarly, cinnamaldehyde and selected PUFA derivatives such as EPEA, DHEA, {gamma}-LEA, 2-AG, 2-AG ether and AEA triggered TRPA1 response, with EPA, DHA, {gamma}-LA, and the 9:3:1 ratio showing significant effects at higher concentrations. ConclusionsPUFAs alone and their combined form in 9:3:1 ratio stimulate TRPA1 activity, whereas their metabolites trigger both TRPV1 and TRPA1 response. These findings suggest new avenues to explore for research into potential mechanisms underlying the neurological benefits of PUFAs and their metabolites.

pharmacology and toxicology↗

bioRxiv2024

Potency, dissociation kinetics and reversibility of fentanyls and nitazenes by naloxone at the μ opioid receptor

Background and PurposeFentanyls and nitazenes are opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we compared the potency, dissociation kinetics and antagonism by naloxone at the receptor of several fentanyl and nitazene analogues and compared them to morphine and DAMGO. Experimental ApproachIn vitro assays of G protein activation and signalling and arrestin recruitment were performed. AtT20 cells expressing receptors were loaded with a membrane potential dye and changes in fluorescence used to determine agonist potency, dissociation kinetics and susceptibility to antagonism by naloxone. BRET experiments were undertaken in HEK293T cells expressing opioid receptors, to assess Gi protein activation and {beta}-arrestin 2 recruitment. Key ResultsThe rate of agonist dissociation from the receptor varied, with morphine, DAMGO, alfentanil and fentanyl dissociating rapidly whereas isotonitazene, etonitazene, ohmefentanyl and carfentanil dissociated slowly. Slowly dissociating agonists were more resistant to antagonism by naloxone. For carfentanil, the slow rate of dissociation was not due to G protein receptor kinase-mediated arrestin recruitment as its rate of dissociation was not affected by inhibition of GRKs with Compound 101. The in vitro relative potencies of fentanyls and nitazenes compared to morphine were much lower than that previously observed in in vivo experiments. Conclusions and ImplicationsWith fentanyls and nitazenes, that slowly dissociate from the opioid receptor, antagonism by naloxone is pseudo competitive. In overdoses involving fentanyls and nitazenes higher doses of naloxone may be required for reversal than those normally used to reverse heroin overdose. What is already knownO_LI"Fentanyls" and "nitazenes" are potent agonists at the opioid receptor. C_LI What does this study addO_LISome fentanyls and nitazenes dissociate slowly and are less sensitive to naloxone antagonism C_LI What is the clinical significanceO_LIMore naloxone may be required to reverse overdoses involving fentanyls and nitazenes C_LI

pharmacology and toxicology↗

bioRxiv2023

Activation of cannabinoid CB2 receptors by (-)-cannabichromene but not (+)-cannabichromene

IntroductionCannabichromene (CBC) is a minor constituent of Cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC (or both) can mediate these effects. In this study we investigate the activity of the CBC enantiomers at CB1, CB2 and TRPA1 in vitro. Materials and MethodsCBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results(-)-CBC activated CB2 with an EC50 of 1.5 {micro}M, to a maximum of 60 % of CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 {micro}M. Only 30 {micro}M (-)- CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)- CBC activated TRPA1; at 30 {micro}M (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 {micro}M), 30 {micro}M (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. DiscussionIt is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in Cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.

pharmacology and toxicology↗

bioRxiv2023

Histidine and its uptake are essential for the growth of Staphylococcus aureus at low pH

Staphylococcus aureus is an opportunistic pathogen capable of causing many different human diseases. During colonization and infection, S. aureus will encounter a range of hostile environments, including acidic conditions such as those found on the skin and within macrophages. However, little is known about the mechanisms that S. aureus uses to detect and respond to low pH. Here, we employed a transposon sequencing approach to determine on a genome-wide level the genes required or detrimental for growth at low pH. We identified 31 genes that were essential for the growth of S. aureus at pH 4.5 and confirmed the importance of many of them through follow up experiments using mutant strains inactivated for individual genes. Most of the genes identified code for proteins with functions in cell wall assembly and maintenance. These data suggest that the cell wall has a more important role than previously appreciated in promoting bacterial survival when under acid stress. We also identified several novel processes previously not linked to the acid stress response in S. aureus. These include aerobic respiration and histidine transport, the latter by showing that one of the most important genes, SAUSA300_0846, codes for a previously uncharacterized histidine transporter. We show that an S. aureus SAUSA300_0846 mutant is unable to maintain its cytosolic pH, thereby revealing an important function for histidine and its transport in buffering the intracellular pH in bacteria. Author summaryStaphylococcus aureus is an important human bacterial pathogen that can cause a range of diseases. During infection, the pathogen will encounter a hostile environment within the human host, including acidic conditions such as those found on the skin and within macrophages. The bacterium has developed sophisticated strategies to survive and grow under such harsh conditions. Here we performed a genome wide screen to identify factors that are required by this pathogen to survive under acid stress conditions and identified several novel processes including histidine uptake. Understanding the response of S. aureus to deal with acid stress conditions will help us better manage infections.

microbiology↗

bioRxiv2021

Interferon Resistance of Emerging SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and four major variants of concern. Our data reveal increased interferon resistance in emerging SARS-CoV-2 variants, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections. Author SummaryIn less than 2 years since its spillover into humans, SARS-CoV-2 has infected over 220 million people, causing over 4.5 million COVID-19 deaths. High infection rates provided substantial opportunities for the virus to evolve, as variants with enhanced transmissibility, pathogenesis, and resistance to vaccine-elicited neutralizing antibodies have emerged. While much focus has centered on the Spike protein which the virus uses to infect target cells, mutations were also found in other viral proteins that might inhibit innate immune responses. Specifically, viruses encounter a potent innate immune response mediated by the interferons, two of which, IFN2 and IFN{beta}, are being repurposed for COVID-19 treatment. Here, we compared the potency of human interferons against ancestral and emerging variants of SARS-CoV-2. Our data revealed increased interferon resistance in emerging SARS-CoV-2 strains that included the alpha, beta, gamma and delta variants of concern, suggesting a significant, but underappreciated role for innate immunity in driving the next phase of the COVID-19 pandemic.

microbiology↗

bioRxiv2020

Modulation of Recombinant Human T-type calcium channels by Δ9-tetrahydrocannabinolic acid in vitro

IntroductionLow voltage-activated T-type calcium channels (T-type ICa), CaV3.1, CaV3.2, and CaV3.3 are opened by small depolarizations from the resting membrane potential in many cells and have been associated with neurological disorders including absence epilepsy and pain. {Delta}9-tetrahydrocannabinol (THC) is the principal psychoactive compound in Cannabis and also directly modulates T-type ICa, however, there is no information about functional activity of most phytocannabinoids on T-type calcium channels, including {Delta}9-tetrahydrocannabinol acid (THCA), the natural non-psychoactive precursor of THC. The aim of this work was to characterize THCA effects on T-type calcium channels. Materials and MethodsWe used HEK293 Flp-In-TREx cells stably expressing CaV3.1, 3.2 or 3.3. Whole-cell patch clamp recordings were made to investigate cannabinoid modulation of ICa. ResultsTHCA and THC inhibited the peak current amplitude CaV3.1 with a pEC50s of 6.0 {+/-} 0.7 and 5.6 {+/-} 0.4, respectively. 1M THCA or THC produced a significant negative shift in half activation and inactivation of CaV3.1 and both drugs prolonged CaV3.1 deactivation kinetics. THCA (10 M) inhibited CaV3.2 by 53% {+/-} 4 and both THCA and THC produced a substantial negative shift in the voltage for half inactivation and modest negative shift in half activation of CaV3.2. THC prolonged the deactivation time of CaV3.2 while THCA did not. THCA inhibited the peak current of CaV3.3 by 43% {+/-} 2 (10M) but did not notably affect CaV3.3 channel activation or inactivation, however, THC caused significant hyperpolarizing shift in CaV3.3 steady state inactivation. DiscussionTHCA modulated T-type ICa currents in vitro, with significant modulation of kinetics and voltage dependence at low M concentrations. This study suggests that THCA may have potential for therapeutic use in pain and epilepsy via T-type channel modulation without the unwanted psychoactive effects associated with THC.

pharmacology and toxicology↗

bioRxiv2020

Modulation of Human T-type Calcium Channels by Synthetic Cannabinoid Receptor Agonists in vitro

BACKGROUND AND PURPOSEConsumption of Synthetic Cannabinoid Receptor agonists (SCRAs) is associated with severe adverse reactions including seizures, arrhythmias and death, but the molecular mechanisms surrounding SCRA toxicity are not yet established. These disease-like symptoms are also synonymous with altered T-type calcium channel activity which controls rhythmicity in the heart and brain. This study examined whether SCRAs alter T-type activity and whether this represents a possible mechanism of toxicity. EXPERIMENTAL APPROACHFluorescence-based and electrophysiology assays were used to screen 16 structurally related synthetic cannabinoids for their ability to inhibit human T-type calcium channels expressed in HEK293 cells. The most potent compounds were then further examined using patch clamp electrophysiology. KEY RESULTSMDMB-CHMICA and AMB-CHMINACA potently blocked Cav3.2 with IC50 values of 1.5 and 0.74 M respectively. Current inhibition increased from 47 to 80% and 45 to 87% respectively when the channel was in slow-inactivated state. Both SCRAs had little effect on steady state inactivation, however MDMB-CHMICA significantly shifted the half activation potential by -7mV. Neither drug produced frequency dependent block, in contrast to the phytocannabinoid {Delta}9-THC. CONCLUSIONS and IMPLICATIONSSCRAs are potent agonists of CB1 receptors and can be extremely toxic, but observed toxicity also resembles symptoms associated with altered Cav3.2 activity. Many SCRAs tested were potent modulators of Cav3.2, raising the possibility that SC toxicity may be due in part to Cav3.2 modulation. This potent T-type channel modulation suggests the possibility of SCRAs as a new drug class with potential to treat diseases associated with altered T-type channel activity.

pharmacology and toxicology↗

bioRxiv2020

Structure and reconstitution of a hydrolase complex that releases peptidoglycan from the membrane after polymerization

Bacteria are surrounded by a peptidoglycan cell wall that is essential for their survival1. During cell wall assembly, a lipid-linked disaccharide-peptide precursor called Lipid II is polymerized and crosslinked to produce mature peptidoglycan. As Lipid II is polymerized, nascent polymers remain membrane-anchored at one end and the other end becomes crosslinked to the matrix2-4. A longstanding question is how bacteria release newly synthesized peptidoglycan strands from the membrane to complete the synthesis of mature peptidoglycan. Here we show that a Staphylococcus aureus cell wall hydrolase and a membrane protein containing eight transmembrane helices form a complex that acts as a peptidoglycan release factor. The complex cleaves nascent peptidoglycan internally to produce free oligomers as well as lipid-linked oligomers that can undergo further elongation. The polytopic membrane protein, which is similar to a eukaryotic CAAX protease, controls the length of these products. A 2.6 [A] resolution structure of the complex shows that the membrane protein scaffolds the hydrolase to orient its active site for cleavage of the glycan strand. We propose that this complex serves to detach newly-synthesized peptidoglycan polymer from the cell membrane to complete integration into the cell wall matrix.

microbiology↗

bioRxiv2019

Differential activation of G protein-mediated signalling by synthetic cannabinoid receptor agonists

Synthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear - including the potential differential activation of G protein subtypes by CB1, a major target of SCRA. We measured CB1-mediated activation of Gs and Gi/o proteins by SCRAs by examining stimulation (PTX-treated) as well as inhibition (non-PTX treated) of forskolin-induced cAMP accumulation in HEK cells stably expressing CB1. Real-time measurements of stimulation and inhibition of cAMP levels were made using a BRET biosensor. We found that the maximum concentration of SCRAs tested (10 M), increased cAMP levels 12 to 45% above that produced by forskolin alone, while the phytocannabinoid THC did not significantly alter cAMP levels in PTX-treated HEK-CB1 cells. All SCRAs had greater potency to inhibit of forskolin-induced cAMP levels than to stimulate cAMP levels. The rank order of potencies for SCRA stimulation of cAMP (Gs) was PB-22 > 5F-MDMB-PICA > JWH-018 > AB-FUBINACA > XLR-11. By contrast, the potency of SCRAs for inhibition of cAMP (Gi/o) was 5F-MDMB-PICA > AB-FUBINACA > PB-22 > JWH-018 > XLR-11. The different rank order of potency of the SCRAs to stimulate Gs-like signalling compared to Gi/o signalling suggests differences in G protein preference between SCRAs. Understanding the apparent differences among these drugs may contribute to unravelling their complex effects in humans.

pharmacology and toxicology↗

bioRxiv2019

High-throughput transposon sequencing highlights cell wall as an important barrier for osmotic stress in methicillin resistant Staphylococcus aureus and underlines a tailored response to different osmotic stressors

Staphylococcus aureus is an opportunistic pathogen that can cause soft tissue infections but is also a frequent cause of foodborne illnesses. One contributing factor for this food association is its high salt tolerance allowing this organism to survive commonly used food preservation methods. How this resistance is mediated is poorly understood, particularly during long-term exposure. In this study, we used TN-seq to understand how the responses to osmotic stressors differ. Our results revealed distinctly different long-term responses to NaCl, KCl and sucrose stresses. In addition, we identified the DUF2538 domain containing gene SAUSA300_0957 (gene 957) as essential under salt stress. Interestingly, a 957 mutant was less susceptible to oxacillin and showed increased peptidoglycan crosslinking. The salt sensitivity phenotype could be suppressed by amino acid substitutions in the transglycosylase domain of the penicillin binding protein Pbp2, and these changes restored the peptidoglycan crosslinking to WT levels. These results indicate that increased crosslinking of the peptidoglycan polymer can be detrimental and highlight a critical role of the bacterial cell wall for osmotic stress resistance. This study will serve as a starting point for future research on osmotic stress response and help develop better strategies to tackle foodborne staphylococcal infections.

microbiology↗