Publications by authors named "Milton H Saier Jr"

Insertions of the transposable element IS5 into its target sites in response to stressful environmental conditions, DNA structures, and DNA-binding proteins are well studied, but how the genomic contexts near IS5's native loci impact its transpositions is largely unknown. Here, by examining the roles of all 11 copies of IS5 within the genome of strain BW25113 in transposition, we reveal that the most significant copy of IS5 is one nested within and oriented in the same direction as the gene, while two other copies of IS5 harboring point mutations are hardly transposed. Transposition activity is heavily reliant on the upstream promoter that drives IS5 transposase gene , with more transpositions resulting from greater promoter activity.

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We propose that intermittent fasting (time-restricted eating), in agreement with the conclusions of other biologists, as revealed in recent publications, promotes the achievement of numerous health benefits including the extension of human and animal lifespans. Background: There is evidence, obtained both with animal model systems and with humans, that intermittent fasting has health benefits. These benefits include extended longevity, weight loss, and counteracting various disease conditions.

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In this report we present seven lines of bioinformatic evidence supporting the conclusion that the Pentameric Ligand-gated Ion Channel (pLIC) Family is a member of the Voltage-gated Ion Channel (VIC) Superfamily. In our approach, we used the Transporter Classification Database (TCDB) as a reference and applied a series of bioinformatic methods to search for similarities between the pLIC family and members of the VIC superfamily. These include: (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) shared domains, (4) conserved motifs, (5) similarity of Hidden Markov Model profiles between families, (6) common 3D structural folds, and (7) clustering analysis of all families.

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The operon in K-12 strain BW25113, encoding the proteins necessary for the uptake and metabolism of β-glucosides, is normally not expressed. Insertion of either IS1 or IS5 upstream of the promoter activates expression of the operon only when the cell is starving in the presence of a β-glucoside, drastically increasing transcription and allowing the cell to survive and grow using this carbon source. Details surrounding the exact mechanism and regulation of the IS insertional event remain unclear.

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Background: The gut microbiome is integral to host health, hosting complex interactions between the host and numerous microbial species in the gastrointestinal tract. Key among the molecular mechanisms employed by gut bacteria are transportomes, consisting of diverse transport proteins crucial for bacterial adaptation to the dynamic, nutrient-rich environment of the mammalian gut. These transportomes facilitate the movement of a wide array of molecules, impacting both the host and the microbial community.

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Wildtype cells cannot grow on L-1,2-propanediol, as the operon within the fucose () regulon is thought to be silent in the absence of L-fucose. Little information is available concerning the transcriptional regulation of this operon. Here, we first confirm that operon expression is highly inducible by fucose and is primarily attributable to the upstream operon promoter, while the promoter within the 3'-end of is weak and uninducible.

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Members of the Piezo family of mechanically activated cation channels are involved in multiple physiological processes in higher eukaryotes, including vascular development, cell differentiation, touch perception, hearing, and more, but they are also common in single-celled eukaryotic microorganisms. Mutations in these proteins in humans are associated with a variety of diseases, such as colorectal adenomatous polyposis, dehydrated hereditary stomatocytosis, and hereditary xerocytosis. Available 3D structures for Piezo proteins show nine regions of four transmembrane segments each that have the same fold.

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The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. Evidence has been provided that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on its way to an endemic form; however, the threat of the virus is more for susceptible (older and immunocompromised) people.

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Allantoin is a good source of ammonium for many organisms, and in Escherichia coli it is utilized under anaerobic conditions. We provide evidence that allantoinase (AllB) is allosterically activated by direct binding of the allantoin catabolic enzyme, glycerate 2-kinase (GlxK) in the presence of glyoxylate. Glyoxylate is known to be an effector of the AllR repressor which regulates the allantoin utilization operons in E.

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Using reporter gene () transcriptional fusions we examined the transcriptional dependencies of the promoter (P) and the entire operon regulatory region (P-) on eight transcription factors as well as the inducer, salicin, and an IS5 insertion upstream of P. Crp-cAMP is the primary activator of both P and the operon, while H-NS is a strong dominant operon repressor but only a weak repressor of P. H-NS may exert its repressive effect by looping the DNA at two binding sites.

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The human population is plagued by hundreds of infectious agents that cause diseases, and many of these agents can infect a range of wild and domesticated animals as well. In fact, a large proportion of current pathological conditions in humans is caused by our close association with nonhuman animals, some of which we keep as pets, but most of which we raise, prepare as food sources, and ingest. It is well established that most of these diseases are caused by a variety of infectious agents, the most important being bacteria, viruses, prions, and protozoans.

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Although Escherichia coli K-12 strains represent perhaps the best known model bacteria, we do not know the identity or functions of all of their transcription factors (TFs). It is now possible to systematically discover the physiological function of TFs in E. coli BW25113 using a set of synergistic methods; including ChIP-exo, growth phenotyping, conserved gene clustering, and transcriptome analysis.

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The human microbiome influences human health in both negative and positive ways. Studies on the transportomes of these organisms yield information that may be utilized for various purposes, including the identification of novel drug targets and the manufacture of improved probiotic strains. Moreover, these genomic analyses help to improve our understanding of the physiology and metabolic capabilities of these organisms.

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Many genes in bacterial genomes are of unknown function, often referred to as y-genes. Recently, the analytic methods have divided bacterial transcriptomes into independently modulated sets of genes (iModulons). Functionally annotated iModulons that contain y-genes lead to testable hypotheses to elucidate y-gene function.

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Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria.

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Upon discovery of the first archaeal species in the 1970s, life has been subdivided into three domains: Eukarya, Archaea, and Bacteria. However, the organization of the three-domain tree of life has been challenged following the discovery of archaeal lineages such as the TACK and Asgard superphyla. The Asgard Superphylum has emerged as the closest archaeal ancestor to eukaryotes, potentially improving our understanding of the evolution of life forms.

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The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of , which metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents.

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family.

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The genus includes species that may inhabit different anatomical locations in the human body, but the greatest percentage of its species are inhabitants of the gut. Lactobacilli are well known for their probiotic characteristics, although some species may become pathogenic and exert negative effects on human health. The transportome of an organism consists of the sum of the transport proteins encoded within its genome, and studies on the transportome help in the understanding of the various physiological processes taking place in the cell.

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Article Synopsis
  • The study investigates how overexpressing certain sugar transport systems in prokaryotes affects the activity of both PTS (phosphotransferase system) and non-PTS transport proteins.
  • It finds that overexpression of specific transporters selectively enhances the uptake rates of various sugars, indicating direct protein-protein interactions between these transporters.
  • Importantly, the overall increase in transport activities does not seem to change the PEP-dependent phosphorylation actions of the PTS systems, suggesting a complex regulatory network among membrane transport proteins.
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For decades it has been known that infectious agents including pathogenic protozoans, bacteria, and viruses, adapted to a particular animal host, can mutate to gain the ability to infect another host, and the mechanisms involved have been studied in great detail. Although an infectious agent in one animal can alter its host range with relative ease, no example of a plant virus changing its host organism to an animal has been documented. One prevalent pathway for the transmission of infectious agents between hosts involves ingestion of the flesh of one organism by another.

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Here we provide bioinformatic evidence that the Organo-Arsenical Exporter (ArsP), Endoplasmic Reticulum Retention Receptor (KDELR), Mitochondrial Pyruvate Carrier (MPC), L-Alanine Exporter (AlaE), and the Lipid-linked Sugar Translocase (LST) protein families are members of the Transporter-Opsin-G Protein-coupled Receptor (TOG) Superfamily. These families share domains homologous to well-established TOG superfamily members, and their topologies of transmembranal segments (TMSs) are compatible with the basic 4-TMS repeat unit characteristic of this Superfamily. These repeat units tend to occur twice in proteins as a result of intragenic duplication events, often with subsequent gain/loss of TMSs in many superfamily members.

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The Major Facilitator Superfamily (MFS) is currently the largest characterized superfamily of transmembrane secondary transport proteins. Its diverse members are found in essentially all organisms in the biosphere and function by uniport, symport, and/or antiport mechanisms. In 1993 we first named and described the MFS which then consisted of 5 previously known families that had not been known to be related, and by 2012 we had identified a total of 74 families, classified phylogenetically within the MFS, all of which included only transport proteins.

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The SLC22 family of OATs, OCTs, and OCTNs is emerging as a central hub of endogenous physiology. Despite often being referred to as "drug" transporters, they facilitate the movement of metabolites and key signaling molecules. An in-depth reanalysis supports a reassignment of these proteins into eight functional subgroups, with four new subgroups arising from the previously defined OAT subclade: OATS1 (SLC22A6, SLC22A8, and SLC22A20), OATS2 (SLC22A7), OATS3 (SLC22A11, SLC22A12, and Slc22a22), and OATS4 (SLC22A9, SLC22A10, SLC22A24, and SLC22A25).

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The multicomponent phosphoenolpyruvate (PEP)-dependent sugar-transporting phosphotransferase system (PTS) in Escherichia coli takes up sugar substrates from the medium and concomitantly phosphorylates them, releasing sugar phosphates into the cytoplasm. We have recently provided evidence that many of the integral membrane PTS permeases interact with the fructose PTS (FruA/FruB) [1]. However, the biochemical and physiological significance of this finding was not known.

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