Comparing Gene Expression Between Planktonic and Biofilm Cells of Foodborne Bacterial Pathogens Through RT-qPCR.

Like most microorganisms, important foodborne pathogenic bacteria, such as Salmonella enterica, Listeria monocytogenes, and several others as well, can attach to surfaces, of either abiotic or biotic nature, and create biofilms on them, provided the existence of supportive environmental conditions (e.g., permissive growth temperature, adequate humidity, and nutrient presence). Inside those sessile communities, the enclosed bacteria typically present a gene expression profile that differs from the one that would be displayed by the same cells growing planktonically in liquid media (free-swimming cells). This altered gene expression has important consequences on cellular physiology and behavior, including stress tolerance and induction of virulence. In this chapter, the methodology to use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to monitor and comparatively quantify expression changes in preselected genes of bacteria between planktonic and biofilm growth modes is presented.

Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity.

BACKGROUND & AIMS: Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic OXPHOS capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases. METHODS: We analysed 65 humans without diabetes (BMI 50±7 kg/m2, HbA1c 5.5±0.4%) undergoing bariatric surgery. MASLD stages were assessed by histology, whole-body insulin sensitivity (PREDIcted-M index) by oral glucose tolerance tests, and maximal ADP-stimulated mitochondrial OXPHOS capacity by high-resolution respirometry of liver samples. RESULTS: Prediabetes was present in 30 participants, and MASLD in 46 participants. Thereof, 25 had metabolic dysfunction-associated steatohepatitis (MASH), and seven had F2-F3 fibrosis. While simple regression did not detect an association of insulin sensitivity with hepatic OXPHOS capacity, interaction analyses revealed that the regression coefficient of OXPHOS capacity depended on fasting plasma glucose (FPG) and liver lipid content. Interestingly, the respective slopes were negative for FPG ≤100 mg/dl, but positive for FPG >100 mg/dl. Liver lipid content displayed similar behavior, with a threshold value of 24%. Post-challenge glycemia affected the association between insulin sensitivity and OXPHOS capacity normalized for citrate synthase activity. Presence of prediabetes affected hepatic insulin signaling, mitochondrial dynamics and fibrosis prevalence, while the presence of MASLD related to higher biomarkers of hepatic inflammation, cell damage and lipid peroxidation in people with normal glucose tolerance. CONCLUSIONS: Rising liver lipid contents and plasma glucose concentrations, even in the non-diabetic range, are associated with a progressive decline of hepatic mitochondrial adaptation in people with obesity and insulin resistance. CLINTRIALS. GOV IDENTIFIER: NCT01477957.

Antimicrobial Tolerance in Cross-Kingdom Dual-Species Biofilms Formed by Fungi and Bacteria.

Candida albicans, the most common pathogenic fungus, can form biofilms on the surface of medical devices and often causes bloodstream infections. Biofilms have a complex structure composed of microorganisms and a surrounding extracellular matrix. Biofilms are difficult to treat because they are resistant to antifungal drugs and the host environment. Nearly one in four patients with candidemia have a polymicrobial infection. These polymicrobial biofilms, especially those comprising cross-kingdom species of fungi and bacteria, can lead to long hospital stays and high mortality rates. This review outlines the unique interactions of dual-species biofilms with Candida albicans and the clinically important bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

The Intake of Dietary Lipids Improves Glucose Tolerance via Modulating Gut Microbiota.

The composition of gut microbiota is determined not only by genetic factors but also by environmental factors, such as diet, exercise, and disease conditions. Among these factors, diet is crucial in changing the gut microbial composition. Dietary lipids composed of different fatty acids not only alter host metabolism but also have a significant impact on the composition of gut microbiota. However, the molecular mechanisms underlying the relationship between these host effects and their impact on gut microbiota remain unclear. Here, we demonstrated that intake of different dietary lipids improved glucose tolerance by modulating gut microbiota. The results of our analysis show that the taxa of bacteria that increase in number as a result of dietary lipid intake play an important role in glucose metabolism. Thus, we have identified a new mechanism underlying the function of dietary lipids in regulating glucose homeostasis. Our findings contribute to possible new methods to prevent and treat metabolic disorders by modifying the composition of gut microbiota.

Quinolone antibiotics stimulate bacterial mercury methylation by Geobacter metallireducens GS-15.

Bacterial mercury (Hg) methylation is critical for bioremediating Hg pollution, but the impact of emerging antibiotics on this process has rarely been reported. This study innovatively investigated the interactions between Hg-methylating bacteria of Geobacter metallireducens GS-15 and two quinolone antibiotics: lomefloxacin (LOM) and ciprofloxacin (CIP) at 5 µg/L. Short-term LOM exposure increased methylmercury (MeHg) yield by 36 % compared to antibiotic-free conditions, caused by hormesis to alter bioactivities of single GS-15 cells. Long-term CIP exposure led to more antibiotic resistance and mercury tolerance in GS-15 cells, doubling MeHg productivity and significantly increasing expression of Hg methylation (hgcA by 95 folds) and antibiotic resistance (gyrA by 54 folds) genes, while mercury resistance gene merA only increased by 2.5 folds than without selective pressure. These results suggest quinolone antibiotics at environmentally contaminated concentrations stimulate bacterial Hg methylation to form highly toxic MeHg, raising considerable concern for the Hg-antibiotic complex in contaminated environments.

Distinct Immune Homeostasis Remodeling Patterns after HLA-Matched and Haploidentical Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely used treatment for a variety of hematopoietic disorders, and also provides a valuable platform for investigating the development of donor-derived immune cells in recipients post-HSCT. The immune system remodels from the donor to the recipient during allo-HSCT. However, little is known about the cell profile alterations as donor homeostasis rebalances to recipient homeostasis following HSCT. Here, multi-omics technology is applied at both the single cell and bulk sample levels, as well as spectrum flow cytometry and fluorescent transgenic mouse models, to dissect the dynamics of the rebalanced homeostatic immune system in recipients after allo-HSCT. The data reveal that all immune subpopulations observed in donors are successfully restored in recipients, though with varying levels of abundance. The remodeling of immune homeostasis exhibits different patterns in HLA-matched and haploidentical HSCT, highlighting distinct biases in T cell reconstitution from the central and peripheral pathways. Furthermore, ZNF683 is critical for maintaining the persistence and quiescence of CD8 T-cell in haploidentical HSCT. The research can serve as a foundation for developing novel strategies to induce immune tolerance.

Low-dose interleukin-2 in patients with bipolar depression: A phase 2 randomised double-blind placebo-controlled trial.

Immune abnormalities including an insufficiency of regulatory T cells (Treg) and increased blood-based inflammatory markers have been observed in bipolar disorders (BD), particularly during depression. As Tregs are pivotal to control inflammation, Treg stimulation by low-dose IL-2 (IL-2LD) could have a therapeutic impact on bipolar depression. We performed a randomized, double-blind, placebo-controlled (2 active: 1 placebo) proof-of-concept trial of add-on IL-2LD in patients with bipolar depression. Patients received a placebo or IL-2LD (1MIU) once a day for 5 days, and then once a week for 4 weeks starting on week 2. The primary objective was to demonstrate a biological Treg response to IL-2LD assessed by fold increase in Treg percentage of CD4 + cells from baseline to day 5. Secondary objectives included safety assessment and mood improvement throughout the study period. This trial is registered with ClinicalTrials.gov, number NCT04133233. Fourteen patients with bipolar depression were included, with 4 receiving placebo and 10 IL-2LD. Baseline clinical and biological characteristics were balanced between groups. The primary evaluation criterion was met, with IL-2LD expanding 1.17 [95 % CI 1.01-1.34] vs 1.01 [95 % CI 0.90-1.12] (p = 0.0421) and activating Tregs. Secondary evaluation criteria were also met with significant improvements of depressive symptoms and global functioning from day-15 onwards in the IL-2LD treated patients. The treatment was well-tolerated, with no serious adverse events related to treatment. This proof-of-concept trial shows that stimulating Tregs in patients with bipolar depression is safe and associated with clinical improvements. This supports a pathophysiological role of inflammation in BD and warrants pursuing the evaluation of IL-2LD as an adjunct treatment of major mood disorders.

Zinc and methyl jasmonate improve sugar beet tolerance to high boron stress by enhanced leaf photochemical performance.

Nutrient imbalances, such as high boron (B) stress, occur within, as well as across, agricultural systems worldwide and have become an important abiotic factor that reduces soil fertility and inhibits plant growth. Sugar beet is a B-loving crop and is better suited to be grown in high B environments, but the methods and mechanisms regarding the enhancement of high-B stress tolerance traits are not clear. The main objective of this research was to elucidate the effects of the alone and/or combined foliar spraying of zinc sulfate (ZnSO4) and methyl jasmonate (MeJA) on the growth parameters, tolerance, and photochemical performance of sugar beet under high-B stress. Results demonstrated that the photosynthetic performance was inhibited under high-B stress, with a reduction of 11.33% in the net photosynthetic rate (Pn) and an increase of 25.30% in the tolerance index. The application of ZnSO4, MeJA, and their combination enhanced sugar beet's adaptability to high-B stress, with an increase in Pn of 9.22%, 4.49%, and 2.85%, respectively, whereas the tolerance index was elevated by 15.33%, 8.21%, and 5.19%, respectively. All three ameliorative treatments resulted in increased photochemical efficiency (Fv/Fm) and the photosynthetic performance index (PIABS) of PSII. Additionally, they enhanced the light energy absorption (ABS/RC) and trapping capacity (DIO/RC), reduced the thermal energy dissipation (TRO/RC), and facilitated the QA to QB transfer in the electron transport chain (ETC) of PSII, which collectively improved the photochemical performance. Therefore, spraying both ZnSO4 and MeJA can better alleviate high-B stress and promote the growth of sugar beet, but the combined spraying effect of ZnSO4 and MeJA is lower than that of individual spraying. This study provides a reference basis for enhancing the ability of sugar beet and other plants to tolerate high-B stress and for sugar beet cultivation in high B areas.

Early-age heat exposure improved growth performance and heat tolerance in broilers.

A total of 440 one-day-old healthy male Arbor Acres broilers were equally assigned to a control group (CTL) and an early-age high-temperature exposure (EHT) group (4 replicates per group, 55 chickens per replicate). At d 3, the broilers in CTL group were reared in the normal temperature 33 ± 1°C, while the broilers in EHT group were exposed to 36 ± 1°C for 24 h. At d 43, all broilers were treated with an acute high temperature 35 ± 1°C for 5 h. The results showed that average daily gain in EHT group was decreased at d 3, but average daily gain in EHT group was increased at d 36 to 42 (P < 0.05). Plasma GLU level in EHT group was lower in broilers at d 7 or facing subsequently high temperature for 5 h (P < 0.05). The relative expression of myogenic differentiation (MyoD) gene in pectoralis major and myogenic factor 5 (Myf5) gene in biceps femoris were significantly improved at d 42 after early-age heat exposure (P < 0.05). Broilers in EHT group have a higher temperature tolerance with a lower mortality than control broilers (P < 0.05). Broilers in EHT group have a lower rectal temperature and a higher comb and ear temperature when facing subsequently acute high temperature than control broilers (P < 0.05). In addition, our study demonstrated that early-age heat exposure significantly decreased the mortality and increased the heat tolerance of broilers when facing an acute short-term heat exposures. Early-age heat exposure increased the process of myogenesis via up-regulating the MyoD and Myf5 gene expression in skeletal muscle, which accelerated average daily gain.

Harnessing the potential of red blood cells in immunotherapy.

Red blood cell (RBC) transfusion represents one of the earliest and most widespread forms of cellular therapy. While the primary purpose of RBC transfusions is to enhance the oxygen-carrying capacity of the recipient, RBCs also possess unique properties that make them attractive vehicles for inducing antigen-specific immune tolerance. Preclinical studies have demonstrated that RBC transfusion alone, in the absence of inflammatory stimuli, often fails to elicit detectable alloantibody formation against model RBC antigens. Several studies also suggest that RBC transfusion without inflammation may not only fail to generate a detectable alloantibody response but can also induce a state of antigen-specific non-responsiveness, a phenomenon potentially influenced by the density of the corresponding RBC alloantigen. The unique properties of RBCs, including their inability to divide and their stable surface antigen expression, make them attractive platforms for displaying exogenous antigens with the goal of leveraging their ability to induce antigen-specific non-responsiveness. This could facilitate antigen presentation to the host's immune system without triggering innate immune activation, potentially enabling the induction of antigen-specific tolerance for therapeutic applications in autoimmune disorders, preventing immune responses against protein therapeutics, or reducing alloreactivity in the setting of transfusion and transplantation.

Octocoral growth rate and mortality along a eutrophication gradient in Cuban reefs.

Octocorals are showing resilience to local and global stressors, while the decline in zooxanthellate corals continues. One of the processes that helps explain this ecological succession is the vertical growth of octocorals, which allows colonies to avoid stressors occurring at the substrate level. However, the growth and survival of octocorals could be affected by eutrophication, similar to what has happened with zooxanthellate corals. For this reason, the growth rate, mortality and survival of two octocoral species were determined along a eutrophication gradient in Cuba. A permanent band transect (250 × 2 m) was established on seven frontal reefs, and marked colonies were monitored for one year. The growth rates in height, width and colony area of Eunicea flexuosa and Plexaura kükenthali were significantly greater in the reefs near the polluted river basins. The eutrophication gradient, water visibility, and sediment accumulation on the bottom explained 36-78% of the variability in the growth of both species. The positive and significant correlations between the growth rate and stable nitrogen isotopes in both species and the microbiological variables, suggest that the contributions of dissolved inorganic nitrogen and organic matter from sewage discharge favor the growth of colonies. The eutrophication gradient did not explain the variability in mortality of either species in the short term, while hydrodynamic stress did. The results of this research highlight the resilience of both species and their ability to grow more rapidly in areas with eutrophic conditions, low water visibility, and greater sediment accumulation on the bottom, which may help explain the abundance of octocorals in the western tropical Atlantic.

Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface.

Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.

MYB Transcription Factor CDC5 Activates CBF3 Expression to Positively Regulates Freezing Tolerance via Cooperating With ICE1 and Histone Modification in Arabidopsis.

The freezing temperature greatly limits the growth, development and productivity of plants. The C-repeat/DRE binding factor (CBF) plays a major role in cold acclimation, enabling plants to increase their freezing tolerance. Notably, the INDUCER OF CBF EXPRESSION1 (ICE1) protein has garnered attention for its pivotal role in bolstering plants' resilience against freezing through transcriptional upregulation of DREB1A/CBF3. However, the research on the interaction between ICE1 and other transcription factors and its function in regulating cold stress tolerance is largely inadequate. In this study, we found that a R2R3 MYB transcription factor CDC5 interacts with ICE1 and regulates the expression of CBF3 by recruiting RNA polymerase II, overexpression of ICE1 can complements the freezing deficient phenotype of cdc5 mutant. CDC5 increases the expression of CBF3 in response to freezing. Furthermore, CDC5 influences the expression of CBF3 by altering the chromatin status through H3K4me3 and H3K27me3 modifications. Our work identified a novel component that regulates CBF3 transcription in both ICE1-dependent and ICE1-independent manner, improving the understanding of the freezing signal transduction in plants.

Research progress on plant stress-associated protein (SAP) family: Master regulators to deal with environmental stresses.

Every year, unfavorable environmental factors significantly affect crop productivity and threaten food security. Plants are sessile; they cannot move to escape unfavorable environmental conditions, and therefore, they activate a variety of defense pathways. Among them are processes regulated by stress-associated proteins (SAPs). SAPs have a specific zinc finger domain (A20) at the N-terminus and either AN1 or C2H2 at the C-terminus. SAP proteins are involved in many biological processes and in response to various abiotic or biotic constraints. Most SAPs play a role in conferring transgenic stress resistance and are stress-inducible. The emerging field of SAPs in abiotic or biotic stress response regulation has attracted the attention of researchers. Although SAPs interact with various proteins to perform their functions, the exact mechanisms of these interactions remain incompletely understood. This review aims to provide a comprehensive understanding of SAPs, covering their diversity, structure, expression, and subcellular localization. SAPs play a pivotal role in enabling crosstalk between abiotic and biotic stress signaling pathways, making them essential for developing stress-tolerant crops without yield penalties. Collectively, understanding the complex regulation of SAPs in stress responses can contribute to enhancing tolerance against various environmental stresses through several techniques such as transgenesis, classical breeding, or gene editing.

Unravelling the secrets of soil microbiome and climate change for sustainable agroecosystems.

The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.

Evaluation of probiotic efficacy of indigenous yeast strain, Saccharomyces cerevisiae Y-89 isolated from a traditional fermented beverage of West Bengal, India having protective effect against DSS-induced colitis in experimental mice.

Increasing awareness regarding health promotion and disease prevention has driven inclusion of fermented foods and beverages in the daily diet. These are the enormous sources of beneficial microbes, probiotics. This study aims to isolate yeast strains having probiotic potential and effectivity against colitis. Initially, ninety-two yeast strains were isolated from Haria, an ethnic fermented beverage of West Bengal, India. Primary screening was done by their acid (pH 4) and bile salt (0.3%) tolerance ability. Four potent isolates were selected and found effective against Entamoeba histolytica, as this human pathogen is responsible to cause colitis. They were identified as Saccharomyces cerevisiae. They showed luxurious growth even at 37 oC, tolerance up to 5% of NaCl, resistance to gastric juice and high bile salt (2.0%) and oro-gastrointestinal transit tolerance. They exhibited good auto-aggregation and co-aggregation ability and strong hydrophobicity. Finally, heat map and principal component analysis revealed that strain Y-89 was the best candidate. It was further characterised and found to have significant protective effects against DSS-induced colitis in experimental mice model. It includes improvement in colon length, body weight and organ indices; reduction in disease activity index; reduction in cholesterol, LDL, SGPT, SGOT, urea and creatinine levels; improvement in HDL, ALP, total protein and albumin levels; decrease in coliform count and restoration of tissue damage. This study demonstrates that the S. cerevisiae strain Y-89 possesses remarkable probiotic traits and can be used as a potential bio-therapeutic candidate for the prevention of colitis.

Multi-metal tolerant Porostereum umbrinoalutaceum isolated from Pleurotus ostreatus fruit body showing root colonization, growth promotion of chilli (Capsicum annuum L.) plant and antagonism against fungal pathogens.

Mushroom associated microbes could be utilized to improve crop productivity providing nutrients, plant growth promoting substances, production of hydrolytic enzymes and protecting plant from biotic and abiotic stress. An endophyte designated as KUFC101 was isolated from fruit body of Pleurotus ostreatus and identified as Porostereum umbrinoalutaceum based on nuclear-rRNA gene sequence analysis. Growth in different culture media, metal tolerance, biochemical characterization and effect on chilli plant growth promotion were studied. The isolate showed best growth in Malt extract medium and least growth in synthetic media. It could tolerate toxic metals (Mg, Ca, Fe, Cu, Mn, Zn and Cd each at 100 ppm concentration). It produced amylase, cellulase, chitinase, pectinase, catecholate type of siderophore and indole acetic acid, and inhibited growth of Alternaria solani and Penicillium citrinum. It could colonize in the rhizosphere of chilli plant and influence growth of chilli plant by improving biomass and metabolite content. Porostereum umbrinoalutaceum KUFC101 could be utilized in formulation of biofertiliser under sustainable agricultural system.

Higher fasting glucose is associated with poorer survival in non-diabetic subjects having ischemia with non-obstructive coronary arteries.

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival.

The bacterial quorum sensing signal 2'-aminoacetophenone rewires immune cell bioenergetics through the Ppargc1a/Esrra axis to mediate tolerance to infection.

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2'-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in murine macrophages' mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (Mpc1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (Esrra). Consequently, Esrra exhibits weakened binding to the Mpc1 promoter. This outcome arises from the impaired interaction between Esrra and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized murine and human macrophages. Exogenously added ATP in infected macrophages restores the transcript levels of Mpc1 and Esrra and enhances cytokine production and intracellular bacterial clearance. Consistent with the in vitro findings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association with PA persistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations and PA persistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the Ppargc1a/Esrra axis in its influence on Mpc1/OXPHOS-dependent energy production and PA clearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.

Identification of Shaker Potassium Channel Family Members and Functional Characterization of SsKAT1.1 in Stenotaphrum secundatum Suggest That SsKAT1.1 Contributes to Cold Resistance.

Stenotaphrum secundatum is an excellent shade-tolerant warm-season turfgrass. Its poor cold resistance severely limits its promotion and application in temperate regions. Mining cold resistance genes is highly important for the cultivation of cold-resistant Stenotaphrum secundatum. Although there have been many reports on the role of the Shaker potassium channel family under abiotic stress, such as drought and salt stress, there is still a lack of research on their role in cold resistance. In this study, the transcriptome database of Stenotaphrum secundatum was aligned with the whole genome of Setaria italica, and eight members of the Shaker potassium channel family in Stenotaphrum secundatum were identified and named SsKAT1.1, SsKAT1.2, SsKAT2.1, SsKAT2.2, SsAKT1.1, SsAKT2.1, SsAKT2.2, and SsKOR1. The KAT3-like gene, KOR2 homologous gene, and part of the AKT-type weakly inwardly rectifying channel have not been identified in the Stenotaphrum secundatum transcriptome database. A bioinformatics analysis revealed that the potassium channels of Stenotaphrum secundatum are highly conserved in terms of protein structure but have more homologous members in the same group than those of other species. Among the three species of Oryza sativa, Arabidopsis thaliana, and Setaria italica, the potassium channel of Stenotaphrum secundatum is more closely related to the potassium channel of Setaria italica, which is consistent with the taxonomic results of these species belonging to Paniceae. Subcellular location experiments demonstrate that SsKAT1.1 is a plasma membrane protein. The expression of SsKAT1.1 reversed the growth defect of the potassium absorption-deficient yeast strain R5421 under a low potassium supply, indicating that SsKAT1.1 is a functional potassium channel. The transformation of SsKAT1.1 into the cold-sensitive yeast strain INVSC1 increased the cold resistance of the yeast, indicating that SsKAT1.1 confers cold resistance. The transformation of SsKAT1.1 into the salt-sensitive yeast strain G19 increased the resistance of yeast to salt, indicating that SsKAT1.1 is involved in salt tolerance. These results suggest that the manipulation of SsKAT1.1 will improve the cold and salt stress resistance of Stenotaphrum secundatum.