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18 recordsLinked to original sources
PubMed2024

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δagr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived "memory" of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Staphylococcus aureus↗
PubMed2024

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Staphylococcus aureus↗
PubMed2026

Inhibitory mechanism of phloretin on the AgrA LytTR domain-agr operon complex formation and its application in beef.

Staphylococcus aureus (S. aureus) represents a major foodborne pathogen whose enterotoxin production poses significant challenges to food safety due to its high environmental resistance and limited efficacy of conventional sterilization. Since the expression of enterotoxins is predominantly governed by the agr quorum sensing system, targeting this regulatory pathway has become a strategic choice for virulence control. This study elucidated the mechanism by which phloretin, a potential quorum sensing inhibitor, interferes with the agr system to attenuate virulence. To achieve this, the recombinant AgrA LytTR domain was expressed and purified, and its interaction with phloretin was characterized using thermal shift assays (TSA), electrophoretic mobility shift assays (EMSA), and molecular dynamics (MD) simulations. The results showed that phloretin specifically binds to the AgrA LytTR domain, enhancing its thermal stability and disrupting AgrA LytTR-agr operon binding by reducing the free energy of interaction between them, without causing significant structural rearrangement. Mechanistic analysis indicated that phloretin sterically hinders key β-sheet turn residues (HIS169, ASN201, ARG233), thereby impairing DNA recognition, downregulating RNAIII transcription, and inhibiting agr signaling. In cooked beef, phloretin significantly inhibited the secretion of enterotoxins and α-hemolysin, while delaying lipid oxidation and protein degradation, and maintaining the meat texture. These findings suggested that phloretin is a multifunctional substance with anti-virulence, antioxidant, and preservative properties, demonstrating its potential as a natural food preservative.

Phloretin↗
PubMed2022

Genomic Study on Blood Culture Isolates From Patients With Staphylococcus Infection-associated Glomerulonephritis.

INTRODUCTION: Staphylococcus infection-associated glomerulonephritis (SAGN), is an autoimmune sequela of infection affecting a subset of infected patients without specific predictive factors, frequently presenting with acute nephritic syndrome and propensity for chronic kidney disease. We performed a comparative genotypic and phenotypic analysis of S. aureus isolates from patients that did and those that did not develop SAGN. METHODS: We had 22 culture-proven cases of SAGN from Ohio State University Wexner Medical Center (OSUWMC) from 2004 to 2016, 9 of 22 being blood cultures, with archived isolates. These, along with blood culture isolates from 12 patients with no clinical evidence of SAGN (between ages 40 to 80 years) over the same period were used for genotyping. For host demographic comparison, we used all available SAGN cases (n = 85, including those with positive cultures other than blood; and patients with kidney biopsies received from referring hospitals) and all OSUWMC patients with positive Staphylococcus cultures without glomerulonephritis (GN) (n = 23,496). RESULTS: Multiple sequence types (STs) suggesting strain diversity was seen in the GN isolates with mainly clonal complexes (CC) 5 and 59. Mutations in the agr operon were identified in significantly higher number of the GN isolates (83%) than non-GN isolates (16%). Significant differences in β-hemolysis and biofilm formation was also observed between the groups. CONCLUSION: The functionality of these agr mutants remains to be seen, but the presently known effects of reduced agr function, namely increased surface adhesins, biofilm formation, and persistent bacteremia could be important microbial factors predisposing to SAGN and testing for them early during infection could help to predict its development.

MRSA↗
PubMedDate not supplied

[New genus of actinomycetes: Excellospora gen. nov].

Morphological, cultural and physiological properties of two strains of soil thermophilic actinomycetes were studied. These strains were compared to the actinomycetes of related genera and were found to be close to Micropolyspora and Actinomadura. However, they differed from both genera by the structure of the sporiferous apparatus, from Micropolyspora by the type of the cell wall, and from Actinomadura by the fatty acid composition of lipids of the mycelium. A new genus of actinomycetes, Excellospora Agre a. Guzeva gen. nov., is suggested on the basis of this study. Two species belonging to the genus Micropolyspora are proposed to assign to the new genus as Excellospora viridinigra and Excellospora rubrobrunea. Since these strains differ from the aforementioned species by the traits used for differentiation of the species of actinomycetes, they are described as a new species of the new genus Excellospora Agre a. Guzeva gen. nov. sp. nov.

Hot Temperature↗
PubMed2026

Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.

UNLABELLED: Catheter-associated urinary tract infections (CAUTIs) are one of the most common hospital-associated infections in the United States, accounting for >1 million cases annually. One CAUTI pathogen, Staphylococcus aureus, is commonly found persisting asymptomatically in the bladder of catheterized individuals, increasing these individuals' risk of developing infection. Importantly, S. aureus is not only associated with severe symptoms during CAUTI, including bacteremia and septic shock, but it also produces a common uropathogen-associated virulence factor, urease. Despite its importance, urease has only been well-studied in another uropathogen, Proteus mirabilis. While previous studies identified three S. aureus urease regulators, including CodY, CcpA, and Agr, the environmental signals required for expression and activity, and the enzyme's contribution to CAUTI have not been explored. In this study, we demonstrate that post-exponential growth and growth in the urinary tract environment significantly induce S. aureus urease expression and activity. Additionally, we identify SigB, SaeR, and SrrA as novel regulators of urease, and further explore the role of CodY, CcpA, and Agr-previously implicated in urease expression-in urease regulation in the urinary tract environment. Impactfully, we found that the urease promoters of clinical isolates contain genomic changes that enhance urease expression. Furthermore, urease contributes to biofilm formation under catheterized urinary tract-like conditions in vitro and dissemination from the bladder to the kidneys in a mouse CAUTI model. Together, our data not only provide insight into the regulatory pathway controlling S. aureus urease but also emphasize the importance of studying these mechanisms in a model that mimics the urinary environment. IMPORTANCE: In this study, we investigate how regulatory pathways coordinate the expression and activity of urease in response to environmental signals present within the catheterized urinary tract. We show that growth during the post-exponential phase and in conditions that mimic the urinary tract increases urease expression and activity. This finding challenges the dogma that Staphylococcus aureus is a "weak" urease producer. We also identified three novel regulators of S. aureus urease-SigB, SrrA, and SaeR-and show that their respective activation signals can modulate urease expression. Additionally, single-nucleotide changes identified in the urease regulatory pathway of clinical urinary catheter-associated isolates enhance urease expression. Finally, urease promotes biofilm formation under conditions that mimic the catheterized urinary tract and dissemination during catheter-associated urinary tract infections (CAUTIs). Our study provides insight into the complex regulatory mechanisms controlling urease in the urinary tract and highlights the role urease plays in S. aureus CAUTI.

Urease↗
PubMed1978

Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion.

The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.

Adolescent↗
PubMed2026

Reconstruction of ancestral plant genomes for inter-crop translational research.

We present Ancestral Genome Reconstruction (AGR), an exploratory framework for the automated inference of "paleogenomes" from large-scale comparative datasets. By analyzing 84 extant angiosperm species, we reconstructed 10 key ancestral angiosperm genomes millions of years old. These reconstructed ancestors were instrumental in (1) estimating when angiosperms emerged, when major botanical families originated, and when shared ancestral whole-genome duplication events occurred; and (2) tracing the evolutionary trajectories of ancestral chromosomes and genes, especially those that may have driven the emergence of key life-history traits (e.g., woody vs. herbaceous, aquatic vs. terrestrial, C3 vs. C4, and symbiotic root-nodulating vs. non-nodulating species). We demonstrated that these paleogenomes serve as tractable backbones for inter-crop translational research. Through an open-access web tool, OrthoViewer, we identified orthologs that have retained the same ancestral genomic context, favoring the identification of genes associated with "phenologs"- orthologous genes across species driving analogous phenotypes, traits, or processes-exemplified by FUWA for yield components, FLC for flowering time, and DDM1 for DNA methylation. Taken together, this study provides a testable paleogenomic workflow, opening novel avenues for integrating evolutionary genomics data into modern climate-smart crop breeding and supporting the agroecological transition.

Genome, Plant↗
PubMed1976

Amino acid transport in isolated rat thymocytes. Effects of divalent cations and ethanol.

In dispersed rat thymocytes neither basal alpha-aminoisobutyric acid influx nor influx stimulated by insulin, prostaglandin theophylline, or butyryl adenosine 3':5'-monophosphate (cyclic AMP) depended on extracellular calcium or magnesium. The divalent cation ionophore A23187 inhibited both basal and stimulated alpha-aminoisobutyric acid influx. The extent to which influx was inhibited depended on ionophore concentration, extracellular calcium concentration, and time but did not depend on extracellular magnesium. Significant inhibition could be detected at an ionophore concentration of 1 muM and maximal inhibition occurred with 6 muM A23187. A23187 increased cellular uptake of calcium and there was good agred calcium uptake and that for ionophore inhibition of alpha-aminoisobutyric acid influx. Incubating cells with A23187 and then adding ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid completely reversed ionophore-stimulated cellular calcum uptake but did not reverse inhibition of alpha-aminoisobutyric acid influx. Thus, A23187 produces irreversible inhibition of alpha-aminoisobutyric acid transport in dispersed rat thymocytes. Ethanol abolished insulin-stimulated alpha-aminoisobutyric acid influx but did not alter basal influx or that stimulated by prostaglandin E1, theophylline, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate. Inhibition could be detected with 0.2% (v/v) ethanol and insulin-stimulated alpha-aminoisobutyric influx was abolished with 1% ethanol. The effect of ethanol occurred immediately and could be reversed completely. This ability of ethanol to inhibit selectively insulin-stimulated alpha-aminoisobutyric acid influx indicates that the mechanism through which insulin stimulates alpha-aminoisobutyric acid influx is functionally distinct from the stimulation produced by cyclic AMP.

Aminoisobutyric Acids↗
PubMed1977

[B-lymphocyte origin of the Reed-Sternberg cell. Immunoelectronmicroscopical arguments (author's transl)].

Some direct and indirect arguments are at present in favour of the B-lymphocyte origin of the Reed-Sternberg (R.S.) cell. Immunoperoxidase methods applied to paraffin sections permit to identify immunoglobulin components in their cytoplasm, but these results are not suffisant to prove that the R.S. cell synthesizes immunoglobulins. We have applied immunoelectronmicroscopic methods to a lymph node in a case of Hodgkin's disease. The results permit us to found intracellular immunoglobulins in the R.S. cell and to evoke a probable synthesis of immunoglobulin by free ribosomes, thus agreing the B-lymphocyte nature hypothesis of the R.S. cell.

B-Lymphocytes↗
PubMed2026

Genome-wide association identifies and validates genomic region controlling grain yield and agronomic traits in extra-early orange maize inbred lines under drought.

In order to meet the expected maize yield by 2050, breeders must work to improve breeding program efficiency by intensifying the implementation of new and improved technologies such as marker-assisted selection (MAS). Dissecting the genomic regions associated with drought tolerance is the first step forward in MAS program deployment for maize improvement under drought stress. Genome-wide association studies (GWAS) were used to investigate and identify quantitative trait loci (QTLs) associated with six traits under drought stress. One hundred and eighty-seven extra-early orange maize inbred lines were evaluated under managed drought stress at Ikenne, in Nigeria, during the 2022 and 2023 dry seasons. The materials were also genotyped using 9355 DArTseq SNP markers and analyzed using the enriched compressed mixed linear model (ECMLM). Enriched compressed mixed linear model was used for association-trait analysis. The ECMLM-based GWAS identified 45 candidate genomic loci associated with the six traits, including five for grain yield, with R2 ranging from 8.79 to 25.3%. Independent validation using the multi-locus 3VmrMLM approach confirmed seven high-confidence genomic loci consistently detected by both methods across grain yield, anthesis-silking interval, ear aspect, and ears per plant, providing additional statistical support for these genomic regions. Candidate gene annotation identified biologically relevant genes underlying the validated loci, including Zm00001eb238250 (protein-serine/threonine phosphatase), Zm00001eb040940 (trehalose-phosphatase), Zm00001eb117820 (homeobox protein knotted-1-like 4), Zm00001eb145560 (zinc ion-binding protein), and Zm00001eb294180 (WRKY DNA-binding domain protein), suggesting their potential roles in drought adaptation and grain productivity. These findings improve our understanding of the genetic architecture of drought tolerance in extra-early orange maize and provide valuable genomic resources for accelerating drought-resilient maize breeding.

Zea mays↗
PubMedDate not supplied

[Origin of adifferentiated variants of Streptomyces roseoflavus in submerged culture].

Adifferentiated Nocardia-like variants (Nv) of Streptomyces roseoflavus var. roseofungini, similar in their cultural characteristics with the variant 1-68 described elsewhere (Nikitina, 1968; Kalakoutskii a. Nikitina, 1976), can be obtained not only in the course of growth of the parent culture on a solid medium containing fructose in the form of secondary colonies, but also during submerged cultivation with stirring. Interruptions in aeration do not affect accumulation of the cells of such variants in the medium. A direct correlation has been established between the amount of biomass and the number of Nv colonies when submerged mycelium is inoculated into a solid medium.

Culture Media↗
PubMedDate not supplied

Conditions for the appearance of adifferentiated nocardioform variants of Streptomyces roseoflavus var. roseofungini.

It was shown that adifferentiated nocardioform variants (NV) of Streptomyces roseoflavus var. roseofungini 1128 may appear in mycelial cell suspensions of submerged actinomycete cultures in water, phosphate buffer, and water with fructose (1%) or glucose (1%), as well as in mycelia of old (10-30 days) cultures on different carbon sources. When sugars, alcohols, or amino acids were added to a medium with fructose, NV formation was inhibited, but not completely suppressed. Fructose was shown to be the most potent factor in the appearance of NV.

Culture Media↗
PubMedDate not supplied

[New elementary structures of actinomycete spores of the genera Actinomadura and Streptomyces].

The structure of spore surfaces was studied by electron microscopy in five species of actinomycetes, and two new types of elementary surface structures were discovered. The surface of spores in Streptomyces regensis consists of long flexible, closely interwoven, band-like structures 25 A wide. Ring-like structures 140--150 A in diameter can be observed on spores of Actinomadura verrucosospora; their clusters resemble grapes and the spore silhouette looks like a cone. Rod-like structures of spores in Streptomyces cavourensis and Str. streptomycini which form an ornament resembling the surface of a basket and tubular strucutres in Str. acrimycini of which hair-shaped spore protrusions are made are similar to the elementary structures of spore surfaces in other actinomycetes.

Microscopy, Electron↗