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1.
Regenerative effects of spring water-derived bacterial lysates on human skin fibroblast in in vitro culture: preliminary results.
Nicoletti, G, Saler, M, Tresoldi, MM, Faga, A, Benedet, M, Cristofolini, M
The Journal of international medical research. 2019;(11):5777-5786
Abstract
OBJECTIVE Previous studies have shown regenerative power of the skin with Comano (Trento, Italy) spring water and resident non-pathogenic microflora. This study investigated the action of bacterial lysates that were isolated from Comano spring water on in vitro culture of human skin fibroblasts. METHODS For this study, we selected the following four bacterial lysates: L1 (closest relative: Rudaea cellulosilytica), L2 (closest relative: Mesorhizobium erdmanii), L3 (closest relative: Herbiconiux ginsengi), and L4 (closest relative: Fictibacillus phosphorivorans). Human fibroblasts were cultured under Dulbecco’s modified Eagle’s medium (DMEM) with bacterial lysates added or DMEM (controls). Cell proliferation was evaluated by spectrophotometric absorbance analysis after the XTT-Microculture Tetrazolium Assay. RESULTS At 24 hours, cultures with L2, L3, and L4 showed a higher absorbance compared with controls. At 48 hours, cultures with L1, L2, and L3 showed slightly lower absorbance compared with controls, and culture with L4 showed a higher absorbance than in the other experimental conditions. At 72 hours, absorbance was lower in cultures with L1, L2, and L3 than in controls, and absorbance was higher in culture with L4 than in the other experimental conditions. CONCLUSIONS Our study indicates a favorable action of Comano spring water microbiota on proliferation of human skin fibroblasts.
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Unravelling the sulphur cycle of marine sediments.
Jørgensen, BB
Environmental microbiology. 2019;(10):3533-3538
Abstract
In this invited paper, I give a personal description of my start as a young scientist studying the sulphur cycle of marine sediments. The initial objective was to quantify the processes experimentally using 35 S as a tracer. The results showed an unexpected large contribution of sulphate reduction to the oxidation of sediment organic matter. This implied that sulphate reducing bacteria can perform complete oxidation of their substrates to CO2 . A quantification of sulphate reducing bacteria compared to measured rates of sulphate reduction revealed that the viable counting techniques available at the time vastly underestimated the true cell numbers. Through our introduction of microsensors for oxygen, sulphide and pH, the microbial oxidation of H2 S could be analysed at high spatial resolution. Studies of the large, filamentous sulphur bacteria revealed surprising adaptations to sulphide oxidation based on anaerobic respiration with nitrate stored in vacuoles.
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Recent Synthetic Approaches and Biological Evaluations of Amino Hexahydroquinolines and Their Spirocyclic Structures.
Abdelmoniem, AM, Mohamed, MF, Abdelmoniem, DM, Ghozlan, SAS, Abdelhamid, IA
Anti-cancer agents in medicinal chemistry. 2019;(7):875-915
Abstract
In this review, the recent synthetic approaches of amino hexahydroquinolines and their spirocyclic structures were highlighted. The synthetic routes include, two-components, three-components or fourcomponents reactions. The two-component [3+3] atom combination reaction represents the simplest method. It involves Michael addition of the electron rich β-carbon of β-enaminones to the activated double bond of cinnamonitriles followed by cyclization to yield hexahydroquinoline compounds. The bioactivity profiles and SAR studies of these compounds were also reviewed with emphasis to the utility of these substances as antimicrobial, anticancer and antitubercular agents, as well as calcium channel modulators.
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4.
Production of HMOs using microbial hosts - from cell engineering to large scale production.
Bych, K, Mikš, MH, Johanson, T, Hederos, MJ, Vigsnæs, LK, Becker, P
Current opinion in biotechnology. 2019;:130-137
Abstract
Human Milk Oligosaccharides (HMOs) constitute an important, highly abundant part of mothers' milk delivering many health benefits to the neonate. Until recently, limited availability of HMOs has prevented their use in infant nutrition and impeded research into their biological effects. The shift from chemical synthesis to biotechnological manufacturing has made them accessible in quantities and at prices that are within reach for commercial applications, including infant formula. It accelerated the studies in the field of pre-clinical and clinical HMO biology. This review gives a short overview of HMO manufacturing from the design and optimization of the microbial cell factory and the production of HMOs in the industrial fermentation process to the purification in the downstream process necessary to obtain a final product. Moreover, the transition from chemistry to biotechnology and the current regulatory landscape and commercialization progress are briefly reviewed.
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5.
Environmental conditions shape the nature of a minimal bacterial genome.
Antczak, M, Michaelis, M, Wass, MN
Nature communications. 2019;(1):3100
Abstract
Of the 473 genes in the genome of the bacterium with the smallest genome generated to date, 149 genes have unknown function, emphasising a universal problem; less than 1% of proteins have experimentally determined annotations. Here, we combine the results from state-of-the-art in silico methods for functional annotation and assign functions to 66 of the 149 proteins. Proteins that are still not annotated lack orthologues, lack protein domains, and/ or are membrane proteins. Twenty-four likely transporter proteins are identified indicating the importance of nutrient uptake into and waste disposal out of the minimal bacterial cell in a nutrient-rich environment after removal of metabolic enzymes. Hence, the environment shapes the nature of a minimal genome. Our findings also show that the combination of multiple different state-of-the-art in silico methods for annotating proteins is able to predict functions, even for difficult to characterise proteins and identify crucial gaps for further development.
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6.
Metabolic Signaling and Spatial Interactions in the Oral Polymicrobial Community.
Miller, DP, Fitzsimonds, ZR, Lamont, RJ
Journal of dental research. 2019;(12):1308-1314
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Abstract
Oral supra- and subgingival biofilms are complex communities in which hundreds of bacteria, viruses, and fungi reside and interact. In these social environments, microbes compete and cooperate for resources, such as living space and nutrients. The metabolic activities of bacteria can transform their microenvironment and dynamically influence the fitness and growth of cohabitating organisms. Biofilm communities are temporally and spatially organized largely due to cell-to-cell communication, which promotes synergistic interactions. Metabolic interactions maintain biofilm homeostasis through mutualistic cross-feeding, metabolic syntrophy, and cross-respiration. These interactions include reciprocal metabolite exchanges that promote the growth of physiologically compatible bacteria, processive catabolism of complex substrates, and unidirectional interactions that are globally important for the polymicrobial community. Additionally, oral bacterial interactions can lead to detoxification of oxidative compounds, which will provide protection to the community at large. It has also been established that specific organisms provide terminal electron acceptors to partner species that result in a shift from fermentation to respiration, thus increasing ATP yields and improving fitness. Indeed, many interspecies relationships are multidimensional, and the net outcome can be spatially and temporally dependent. Cross-kingdom interactions also occur as oral yeast are antagonistic to some oral bacteria, while numerous mutualistic interactions contribute to yeast-bacterial colonization, fitness in the oral community, and the pathogenesis of caries. Consideration of this social environment reveals behaviors and phenotypes that are not apparent through the study of microbes in isolation. Here, we provide a comprehensive overview of the metabolic interactions that shape the oral microbial community.
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7.
Genomic analysis of siderophore β-hydroxylases reveals divergent stereocontrol and expands the condensation domain family.
Reitz, ZL, Hardy, CD, Suk, J, Bouvet, J, Butler, A
Proceedings of the National Academy of Sciences of the United States of America. 2019;(40):19805-19814
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Abstract
Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the β-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes of nonheme Fe(II)/α-ketoglutarate-dependent aspartyl β-hydroxylases are identified in siderophore biosynthetic gene clusters, which differ in genomic organization-existing either as fused domains (IβHAsp) at the carboxyl terminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TβHAsp)-and each directs opposite stereoselectivity of Asp β-hydroxylation. The predictive power of this subtype delineation is confirmed by the stereochemical characterization of β-OHAsp residues in pyoverdine GB-1, delftibactin, histicorrugatin, and cupriachelin. The l-threo (2S, 3S) β-OHAsp residues of alterobactin arise from hydroxylation by the β-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) β-OHAsp in delftibactin arises from the stand-alone β-hydroxylase DelD. Cupriachelin contains both l-threo and l-erythro β-OHAsp, consistent with the presence of both types of β-hydroxylases in the biosynthetic gene cluster. A third subtype of nonheme Fe(II)/α-ketoglutarate-dependent enzymes (IβHHis) hydroxylates histidyl residues with l-threo stereospecificity. A previously undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, named the interface domain, which is proposed to position the β-hydroxylase and the NRPS-bound amino acid prior to hydroxylation. Through mapping characterized β-OHAsp diastereomers to the phylogenetic tree of siderophore β-hydroxylases, methods to predict β-OHAsp stereochemistry in silico are realized.
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Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified.
Bruno, G, Zaccari, P, Rocco, G, Scalese, G, Panetta, C, Porowska, B, Pontone, S, Severi, C
World journal of gastroenterology. 2019;(22):2706-2719
Abstract
Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.
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Mechanisms protecting host cells against bacterial pore-forming toxins.
Brito, C, Cabanes, D, Sarmento Mesquita, F, Sousa, S
Cellular and molecular life sciences : CMLS. 2019;(7):1319-1339
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Abstract
Pore-forming toxins (PFTs) are key virulence determinants produced and secreted by a variety of human bacterial pathogens. They disrupt the plasma membrane (PM) by generating stable protein pores, which allow uncontrolled exchanges between the extracellular and intracellular milieus, dramatically disturbing cellular homeostasis. In recent years, many advances were made regarding the characterization of conserved repair mechanisms that allow eukaryotic cells to recover from mechanical disruption of the PM membrane. However, the specificities of the cell recovery pathways that protect host cells against PFT-induced damage remain remarkably elusive. During bacterial infections, the coordinated action of such cell recovery processes defines the outcome of infected cells and is, thus, critical for our understanding of bacterial pathogenesis. Here, we review the cellular pathways reported to be involved in the response to bacterial PFTs and discuss their impact in single-cell recovery and infection.
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10.
Meta-analysis of risk factors for amputation in diabetic foot infections.
Sen, P, Demirdal, T, Emir, B
Diabetes/metabolism research and reviews. 2019;(7):e3165
Abstract
BACKGROUND Knowledge of risk factors is crucial to develop management and treatment protocols for the prevention of lower extremity amputation for patients with diabetic foot infections (DFIs). METHODS We searched the research literature for studies reporting risk factors for lower extremity amputation in patients with DFI. The main outcome variables included both minor and major amputations. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, and the protocol was registered in PROSPERO (CRD42018118543). RESULTS A total of 2471 potential articles from the database search met the inclusion criteria. After reviewing the titles, abstracts, and full texts, remaining 25 articles were included in the final analysis. We identified 6132 patients with DFI in the 25 included articles. Of these, 1873 patients who underwent amputation were investigated. Male gender (odds ratio [OR]: 1.31), smoking (OR: 1.38), history of amputation (OR: 1.47), history of osteomyelitis (OR: 1.94), peripheral arterial disease (OR: 2.35), retinopathy (OR: 1.32), International Working Group on the Diabetic Foot (IWGDF) grades 3 and 4 (OR: 1.7 and 2.5), Wagner grades 4 and 5 (OR: 4.3 and 6.4), gangrene/necrosis (OR: 9.9), osteomyelitis (OR: 4.5), neuroischaemic DFI (OR: 3.06), severe infection (OR: 3.12), length of hospitalization (standardized mean difference [SMD]: 0.7), leukocytosis (OR: 1.76), mean erythrocyte sedimentation rate (ESR) (SMD: 0.5), mean C-reactive protein (CRP) (SMD: 0.8), tissue culture positivity (OR: 1.61), and isolation of Gram-negative bacteria from tissue culture (OR: 1.5) were found as predictors of amputation in DFI. CONCLUSIONS The present study highlighted some differences in diabetic foot ulcers and DFIs in terms of risk factors for lower extremity amputation. These data provide detailed information about risk factors for amputations among patients with DFI, thus contributing to the creation of new classification systems for assessment of high-risk patients.