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BioEMMA: Automated Generation of Model-Specific Escher-Compatible Maps from KEGG Pathways.

Genome-scale metabolic models are widely used to investigate cellular metabolism, but their interpretation and comparison are limited by the lack of reproducible pathway-level visualizations with a common spatial organization. This study presents BioEMMA, a Python-based tool for the automated generation of model-specific metabolic pathway maps in the Escher JSON format using coordinate information from curated KEGG pathway maps. BioEMMA parses KGML files, map reaction and metabolite identifiers to model database namespaces, filters pathway elements according to an input SBML model, adds non-primary metabolites, reconstructs Escher-compatible layouts, and supports flux visualization. The tool was integrated into a reproducible BioUML workflow for metabolic model reconstruction. BioEMMA was evaluated using the e_coli_core model and the KEGG glycolysis/gluconeogenesis pathway while generating a model-specific map with overlaid FBA fluxes. It was then applied to compare E. coli reconstructions generated by gapseq, ModelSEEDpy, and Reconstructor across three central carbon metabolism pathways. To broaden the evaluation, BioEMMA was applied using 87 prokaryotic BiGG models and three eukaryotic models. The analysis revealed pathway-specific differences in reaction coverage, shared and model-specific reactions, and predicted flux activity. BioEMMA therefore provides a reproducible framework for pathway-level visualization and comparison of genome-scale metabolic reconstructions within a common spatial coordinate system.

Escher maps

[Mathematical model of tryptophan synthesis and excretion into the environment by E. coli cells].

A quantitative kinetic model is suggested for the auto-regulated tryptophan synthesis by E. coli trp-operon system and for tryptophan excretion from the cell mediated by transport systems. Applications of the model for the calculation of several parameters characterizing tryptophan metabolism are considered. In order to explain experimental data it is suggested that a system of tryptophane excretion from the cell exists which is induced by high tryptophan concentrations. The rate of tryptophan excretion was studied as a function of various genetic effects (derepression or reduction of retroinhibition) as well as of changes in intracellular concentrations of substrates of tryptophan synthesis (chorismic acid and serine). Possible ways of making the cell to excrete markedly higher quantities of tryptophan without changing the genotype are discussed.

Biological Transport

Modelling peak microbial pollution events caused by combined sewer overflows in a source-to-sea system.

Predicting peak microbial pollution events in downstream coastal bathing waters caused by combined sewer overflows (CSOs) is essential for protecting public health. In urban areas, wastewater effluents, CSOs, and surface runoff can contribute to elevated microorganism loads to downstream waters. These pressures are likely to be intensified by growing population density and more frequent heavy rainfalls due to climate change. This study developed a process-based model to simulate Escherichia coli (E. coli) emissions, transport, and fate from the initial sources to coastal beaches. A three-year retrospective simulation (2017-2019) shows that E. coli concentrations in CSO discharges varied widely across the catchment (4.6 - 7.3 (log10 CFU 100 ml-1)). 99th percentile E. coli concentrations (4.0 (log10 CFU 100 ml-1)) at the inland water outlet were dominated by local CSO emissions, whereas 90th percentile E. coli concentrations (3.6 (log10 CFU 100 ml-1)) reflected cumulative upstream contributions from both CSO and effluent emissions. With the simulation accuracy of 89%, the model reliably reproduced the E. coli dynamics on the downstream beach and showed strong performance in representing peak concentrations based on Complementary Cumulative Distribution Function (CCDF) analysis. The process-based model enables quantitative tracking of source contributions and identification of pollution hotspots, providing support for mitigation measures. The study lays down a source-to-sea modelling framework for representing pollution transport across the aquatic continuum and provides a transferable tool for microbial pollution forecasting and climate adaptation planning.

Climate projection

Experimental E. coli arthritis in the rabbit. A model of infectious and post-infectious inflammatory synovitis.

Rabbit knee joints challenged with E. coli 06 underwent a self-limited infection lasting several weeks followed by a prolonged post-infectious inflammatory arthritis. The E. coli used did not possess collagenolytic activity nor did a variety of common aerobic clinical isolates. Articular cartilage destruction occurred by two basically different mechanisms: u) direct invasion of pannus at the juxtaarticular margins, and 2) fibrillation in cartilage to cartilage contact areas. Weekly measurement of intra-articular pH and temperature were correlated with bacteriologic findings and groww and microscopic pathologic events.

Animals

Probiotic Lacticaseibacillus casei 2S-1 Attenuates Escherichia coli-Induced Enteritis via Gut Microbiota Modulation and Host Gene Regulation.

Maintaining gut microbial homeostasis is crucial for host health, whereas infection with Escherichia coli (E. coli) is a major contributor to intestinal inflammation and microbial dysbiosis. Recent research has focused on probiotic strategies for managing enteric inflammatory disorders. Previous studies have shown that beneficial microorganisms show protection through modulating host immune responses, enhancing intestinal epithelial barrier integrity, and inhibiting pathogenic bacteria. To evaluate the prophylactic effectiveness of a recently isolated strain, Lacticaseibacillus casei 2S-1, in a murine model of E. coli-induced enteritis, this study focuses on interactions within the microbiota-intestinal-immune axis, together with host transcriptional responses and pathway enrichment associated with oxidative stress and mitochondrial function. In vitro analysis of probiotic features, including growth dynamics, acidogenic capacity, and tolerance to acidic and bile salt environments, as well as genetic safety profiling, followed the methodical isolation and taxonomic identification of L. casei 2S-1. A preventive intervention protocol was established, and a murine model of enteritis was induced by exposure to E. coli. Histopathological analyses were performed to observe in vivo safety and protective efficacy. Changes in gut microbial structure were characterized by 16S rRNA gene sequencing, while host responses were identified by intestinal immunohistochemistry and transcriptome profiling. L. casei 2S-1 showed probiotic properties. In vitro analyses showed that the strain exhibited tolerance to acidic and bile salt conditions, and its untreated culture supernatant showed antimicrobial activity against pathogenic bacteria. Its safety profile was supported by genomic analysis, which verified the lack of virulence-associated genes and antibiotic resistance factors. In vivo, L. casei 2S-1 pretreatment reduced mortality and intestinal inflammation, modulated gut microbial composition, and preserved intestinal barrier-associated protein expression in infected mice. This study provides experimental evidence supporting the prophylactic effects of L. casei 2S-1 and its associations with gut microbiota modulation and host transcriptional responses, providing a foundation for further investigation of probiotic-based preventive strategies against intestinal infections.

Animals

Fluorine-19 nuclear magnetic resonance studies of Escherichia coli membranes.

Several fluorinated fatty acids of the general structure CH3(CH2)13--mCF2(CH2)m--2COOH are incorporated biosynthetically as unsaturated fatty acid analogues into the phospholipids of Escherichia coli. Under optimum conditions an unsaturated fatty acid autotroph, K1060B5, can be grown so that 50% of the total phospholipid fatty acids are 8,8-difluoromyristate. Conditions are found for which more than 20% of the fatty acids are fluorinated before a decrease in growth rate is observed. We have used 19F nuclear magnetic resonance to examine membranes isolated from E. coli grown under the latter conditions. A comparison is made with spectra of aqueous dispersions of extracted E. coli phospholipids and model multilayer phospholipid membranes. An explanation of the 19F resonance line shape in these membrane systems and the relationship to a molecular order parameter is given. It is apparent that 19F nuclear magnetic resonance is more sensitive to the degree of ordering or fluidity of phospholipids than spin labels or fluorescent probes. For instance, a dramatic effect of membrane protein on lipid fluidity can be seen. Finally, this method can be used to measure the proportion of frozen and fluid lipid in biological membranes at temperatures within the span of the gel-to-lipid phase transition.

Cell Membrane

Antibiotic activity of cefazedone in experimental pyelonephritis.

The new cephalosporin derivative (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) has been tested for antibacterial activity in the infection and therapy model of acute E. coli pyelonephritis in rats. The reference substance was cephalothin. The tests showed a superiority of cefazedone which, however, could not be clearly confirmed by the significance test. Owing to its favourable pharmacokinetics in combination with good antibacterial activity, cefazedone can be added to the cephalosporins considered for use in clinical practice, especially so as the statistics for 1977 show that the causative agents of pyelonephritis which these drugs can often combat effectively are present in the majority of the urine strains: E. coli accounted for 45%, enterococci for 18%, and Proteus for 15% out of a total number of 6100 urine strains.

Animals

[Significance of the ability of E. coli to alter capillary permeability for the reproduction of pyelonephritis in mice].

Experiments in a number of biological models showed that the cultures of E. coli isolated from the urine of children with pyelonephritis had a varied spectrum of pathogenic properties. Histologically confirmed pyelonephritis induced by intravenous infection in CBA mice, treated with 5% glucose by the method of Montgomerie et al., correlated with the bacterial adhesiveness to the epithelium and the interference with capillary permeability, registered in experiments on the pulmonary model with Evans blue used for control. The criterion for the development of pyelonephritis in mice, which was based, in the opinion of Mintogemerie et al., on the positive results, indicating the presence of the infecting agent in the culture obtained by inoculation with the samples of urine and kidney tissue, was found to be insufficient, as only 28 out of 45 cultures of E. coli isolated from the kidneys coincided with histologically confirmed cases of pyelonephritis.

Animals

Neonatal meningitis due of Escherichia coli K1.

Human neonates are uniquely susceptible to serious infections due to Escherichia coli. Investigation of the serotypes of E. coli isolated from neonates with meningitis revealed that greater than 80% of the isolates possessed the capsular polysaccharide antigen designated K1. Cultures of stool from healthy infants, children, and adults have shown that K1 organisms are commonly found in individuals of all ages. Studies of mother-infant pairs have demonstrated transmission of K1 strains from mother to infant shortly after birth. In the rare infant who develops meningitis due to E. coli K1, serotype analysis frequently reveals that the same organism was isolated from the infant's cerebrospinal fluid and from the stools of both mother and infant. Preliminary investigations of humoral immunity demonstrated an age-related acquisition of antibodies to the capsular polysaccharide of E. coli K1 in healthy infants and children. An animal model was developed in which feeding of E. coli K1 to infant rats resulted in colonization, bacteremia, and meningitis in the animals.

Adult

3'End labelling of RNA with 32P suitable for rapid gel sequencing.

A new general method of labelling the 2',3'-diol end of RNA with 32P has been devised suitable for gel sequencing. Poly(A) polymerase (E. coli) is incubated with the RNA and limiting amounts of alpha-32P-ATP. The mono-addition product is then cleaved with periodate and beta-eliminated with aniline, leaving the RNA terminally labelled with 3' 32P-phosphate. When applied to a model compound, tRNAPhe from E. coli, over 28 residues could be read from the 3' end.

Adenosine Triphosphate

[Use of mathematical recombination models for mapping Escherichia coli K-12 markers].

The possibility is discussed of mapping the E. coli K-12 markers on the basis of mathematical models of recombination previously developed by the authors. The analysis showed that it is advisable to use the symmetrical crossing-over model for mapping the genes close to the selective marker. The stochastic model of recombination gives good results also for genes located in the proximal part of the chromosome.

Chromosome Mapping

The activity of polymyxins against Escherichia coli in an in-vitro model of the urinary bladder.

The activities against a strain of Escherichia coli of polymyxin B, colistin (polymyxin E) and their sulphomethyl derivatives sulphomyxin and colistin sulphomethate have been examined in an in-vitro model of the urinary bladder under conditions similar to those that may operate in the therapeutic situation. In the dynamic conditions of the model, polymyxins exhibited a reduced activity against E. coli in comparison with activity against exponentially growing cultures in a static system. Nevertheless, long-term suppression of bacterial growth was achieved with levels of polymyxin B and colistin that can be attained during therapy, whereas sulphomethylpolymyxins had little effect on bacterial growth even on prolonged exposure.

Bacteriolysis

Some characteristics of Escherichia coli strains isolated from extraintestinal infections of humans.

Escherichia coli strains isolated from extraintestinal infections of humans possess a constellation of phenotypes not usually found in random fecal isolates, enteropathogenic strains, or the laboratory strain E. coli K12. The phenotypes found more commonly in extraintestinal strains include hemolysin production, the biosynthesis of colicin V, and the hemagglutination of human erythrocytes in the presence of D-mannose (HAh). Hemolysin is assumed to be a cytotoxic factor, colicin V is assumed to interfere with host defense mechanisms, and HAh is assumed to play a role in specific tissue adherence. In addition, greater than or equal to 50% of E. coli strains from extraintestinal infections kill allantoically inoculated 13-day-old chick embryos. Some (20%) of the fecal E. coli also kill embryos, but E. coli K12 is innocuous in this virulence model. The plasmids for hemolysin and colicin V production have been transmitted to E. coli K12 derivatives but are not sufficient to convert laboratory strains to a form virulent for the chick embryo.

Adhesiveness

Metagenomic analyses reveal E. coli-derived siderophores as potential signatures for breast cancer.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality in women. Recent evidence implicates the gut microbiome and metabolites in breast cancer pathogenesis. This study explores associations between gut microbial species, their predicted metabolites, and breast cancer to uncover potential mechanistic insights. METHODS: Comprehensive metagenomic analyses were conducted on the gut microbiome of pre- and postmenopausal breast cancer patients, where microbial species were profiled through AMPHORA2 and metabolites were predicted through antiSMASH. Multivariate association analysis was used to identify significant associations between specific microbial species, predicted metabolites, and breast cancer status. A custom ensemble machine learning classifier was developed to classify pre- and postmenopausal breast cancer cases and controls based on microbial and predicted metabolite features. Additionally, a synthetic microbiome dataset was generated through MIDASim to validate the reproducibility of the ML results. Using our results, we explored the underlying dynamics of identified taxa and metabolite in breast cancer through literature and statistical support. RESULTS: Our analysis identified 471 microbial species and predicted 40 key metabolites in the metagenomic data. Multivariate analysis identified significant positive associations (p-value&#x2009;<&#x2009;0.05) of E. coli, siderophore, and thiopeptide with breast cancer. The custom ensemble model achieved accuracy and AUC as high as 78% and 90%, respectively, in classifying pre- and postmenopausal cases and controls. The high-ranking features i.e., E. coli, siderophore, and thiopeptide were consistent with the results of the multivariate association analysis, thereby substantiating their biological significance. Using these findings, we propose a mechanistic model in which E. coli secretes siderophores under iron-limited conditions in breast cancer patients, for iron sequestration from the host, which can potentially promote angiogenesis and tumor progression. CONCLUSION: Our findings suggest that microbial iron acquisition mechanisms may play a critical role in breast cancer pathophysiology. Functional validation of these mechanisms is needed to assess therapeutic potential. This study highlights gut microbiota and their metabolites as promising targets for breast cancer research and intervention.

Breast Neoplasms

Lidocaine treatment following baboon endotoxin shock improves survival.

Baboons treated with lidocaine (2 mg/kg/hr) after shock from endotoxin were compared to untreated controls in an LD70 E coli endotoxin (4 mg/kg) model. Survival, systemic and pulmonary arterial pressures, cardiac output, white blood cell and platelet counts, blood gases and arterial and mixed venous PGE and PGF 2 alpha levels were determined. Baboons receiving lidocaine had a better (P less than 0.05) survival at 72 hours than the controls. Circulatory function was improved with lidocaine; however, white blood cell and platelet counts, blood gases, and the prostaglandin release were similar in both groups. The mechanism by which lidocaine improves survival in baboon endotoxin shock appears to be unrelated to its effects on white blood cells, platelets, or the prostaglandin release.

Animals

A contemporary review of incidence and detection of enterotoxigenic E. coli strains in human diarrheal diseases.

Methodical possibilities for detection of enterotoxic strains of E. coli and the frequency of appearence of these strains in infants and adults suffering from diarrheal diseases are reviewed. Our own study, using the ligated rabbit intestinal loop, revealed 6.8% incidence of enterotoxin producing strains among the classical enteropathogenic serotypes of E. coli, isolated from stools of infants with mild diarrhoea. The model of mice intestinal loop was not found to be suitable for detection of enterotoxin of E. coli strains. The most sensitive model seems to be the intestine of precolostral piglet; however this model is not suitable for routine tests.

Acute Disease