• Design and characterization of dietary assessment in the German National Cohort.

      Knüppel, Sven; Clemens, Matthias; Conrad, Johanna; Gastell, Sylvia; Michels, Karin B; Leitzmann, Michael; Krist, Lilian; Pischon, Tobias; Krause, Gerard; Ahrens, Wolfgang; et al. (Springer Nature, 2019-01-15)
      BACKGROUND/OBJECTIVES: The aim of the study was to describe a novel dietary assessment strategy based on two instruments complemented by information from an external population applied to estimate usual food intake in the large-scale multicenter German National Cohort (GNC). As proof of concept, we applied the assessment strategy to data from a pretest study (2012-2013) to assess the feasibility of the novel assessment strategy. SUBJECTS/METHODS: First, the consumption probability for each individual was modeled using three 24 h food lists (24h-FLs) and frequencies from one food frequency questionnaire (FFQ). Second, daily consumed food amounts were estimated from the representative German National Nutrition Survey II (NVS II) taking the characteristics of the participants into account. Usual food intake was estimated using the product of consumption probability and amounts. RESULTS: We estimated usual intake of 41 food groups in 318 men and 377 women. The participation proportion was 100, 84.4, and 68.5% for the first, second, and third 24h-FL, respectively. We observed no associations between the probability of participating and lifestyle factors. The estimated distributions of usual food intakes were plausible and total energy was estimated to be 2707 kcal/day for men and 2103 kcal/day for women. The estimated consumption frequencies did not differ substantially between men and women with only few exceptions. The differences in energy intake between men and women were mostly due to differences in estimated daily amounts. CONCLUSIONS: The combination of repeated 24h-FLs, a FFQ, and consumption-day amounts from a reference population represents a user-friendly dietary assessment approach having generated plausible, but not yet validated, food intake values in the pretest study
    • Deep sequencing of biofilm microbiomes on dental composite materials.

      Conrads, Georg; Wendt, Laura Katharina; Hetrodt, Franziska; Deng, Zhi-Luo; Pieper, Dietmar; Abdelbary, Mohamed M H; Barg, Andree; Wagner-Döbler, Irene; Apel, Christian (2019-01-01)
      Background: The microbiome on dental composites has not been studied in detail before. It has not been conclusively clarified whether restorative materials influence the oral microbiome. Methods: We used Illumina Miseq next-generation sequencing of the 16S V1-V2 region to compare the colonisation patterns of bovine enamel (BE) and the composite materials Grandio Flow (GF) and Grandio Blocs (GB) after 48 h in vivo in 14 volunteers. Applying a new method to maintain the oral microbiome ex vivo for 48 h also, we compared the microbiome on GF alone and with the new antimicrobial substance carolacton (GF+C). Results: All in vitro biofilm communities showed a higher diversity and richness than those grown in vivo but the very different atmospheric conditions must be considered. Contrary to expectations, there were only a few significant differences between BE and the composite materials GB and GF either in vivo or in vitro: Oribacterium, Peptostreptococcaceae [XI][G-1] and Streptococcus mutans were more prevalent and Megasphaera, Prevotella oulorum, Veillonella atypica, V. parvula, Gemella morbillorum, and Fusobacterium periodonticum were less prevalent on BE than on composites. In vivo, such preferences were only significant for Granulicatella adiacens (more prevalent on BE) and Fusobacterium nucleatum subsp. animalis (more prevalent on composites). On DNA sequence level, there were no significant differences between the biofilm communities on GF and GF+C. Conclusion: We found that the oral microbiome showed an increased richness when grown on various composites compared to BE in vitro, but otherwise changed only slightly independent of the in vivo or in vitro condition. Our new ex vivo biofilm model might be useful for pre-clinical testing of preventive strategies.
    • An Unprecedented Medium-Chain Diunsaturated -acylhomoserine Lactone from Marine Group Bacteria.

      Ziesche, Lisa; Wolter, Laura; Wang, Hui; Brinkhoff, Thorsten; Pohlner, Marion; Engelen, Bert; Wagner-Döbler, Irene; Schulz, Stefan; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MPDI, 2018-12-31)
      N-acylhomoserine lactones (AHLs), bacterial signaling compounds involved in quorum-sensing, are a structurally diverse group of compounds. We describe here the identification, synthesis, occurrence and biological activity of a new AHL, N-((2E,5Z)-2,5-dodecadienoyl)homoserine lactone (11) and its isomer N-((3E,5Z)-3,5-dodecadienoyl)homoserine lactone (13), occurring in several Roseobacter group bacteria (Rhodobacteraceae). The analysis of 26 strains revealed the presence of 11 and 13 in six of them originating from the surface of the macroalgae Fucus spiralis or sediments from the North Sea. In addition, 18 other AHLs were detected in 12 strains. Compound identification was performed by GC/MS. Mass spectral analysis revealed a diunsaturated C12 homoserine lactone as structural element of the new AHL. Synthesis of three likely candidate compounds, 11, 13 and N-((2E,4E)-2,4-dodecadienoyl)homoserine lactone (5), revealed the former to be the natural AHLs. Bioactivity test with quorum-sensing reporter strains showed high activity of all three compounds. Therefore, the configuration and stereochemistry of the double bonds in the acyl chain seemed to be unimportant for the activity, although the chains have largely different shapes, solely the chain length determining activity. In combination with previous results with other Roseobacter group bacteria, we could show that there is wide variance between AHL composition within the strains. Furthermore, no association of certain AHLs with different habitats like macroalgal surfaces or sediment could be detected. View Full-Text
    • Metatranscriptome Analysis of the Vaginal Microbiota Reveals Potential Mechanisms for Protection against Metronidazole in Bacterial Vaginosis.

      Deng, Zhi-Luo; Gottschick, Cornelia; Bhuju, Sabin; Masur, Clarissa; Abels, Christoph; Wagner-Döbler, Irene; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-06-27)
      Bacterial vaginosis (BV) is a prevalent multifactorial disease of women in their reproductive years characterized by a shift from the
    • Tracking gene expression and oxidative damage of O-stressed Clostridioides difficile by a multi-omics approach.

      Neumann-Schaal, Meina; Metzendorf, Nicole G; Troitzsch, Daniel; Nuss, Aaron Mischa; Hofmann, Julia Danielle; Beckstette, Michael; Dersch, Petra; Otto, Andreas; Sievers, Susanne; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-31)
      Clostridioides difficile is the major pathogen causing diarrhea following antibiotic treatment. It is considered to be a strictly anaerobic bacterium, however, previous studies have shown a certain and strain-dependent oxygen tolerance. In this study, the model strain C. difficile 630Δerm was shifted to micro-aerobiosis and was found to stay growing to the same extent as anaerobically growing cells with only few changes in the metabolite pattern. However, an extensive change in gene expression was determined by RNA-Seq. The most striking adaptation strategies involve a change in the reductive fermentation pathways of the amino acids proline, glycine and leucine. But also a far-reaching restructuring in the carbohydrate metabolism was detected with changes in the phosphotransferase system (PTS) facilitated uptake of sugars and a repression of enzymes of glycolysis and butyrate fermentation. Furthermore, a temporary induction in the synthesis of cofactor riboflavin was detected possibly due to an increased demand for flavin mononucleotid (FMN) and flavin adenine dinucleotide (FAD) in redox reactions. However, biosynthesis of the cofactors thiamin pyrophosphate and cobalamin were repressed deducing oxidation-prone enzymes and intermediates in these pathways. Micro-aerobically shocked cells were characterized by an increased demand for cysteine and a thiol redox proteomics approach revealed a dramatic increase in the oxidative state of cysteine in more than 800 peptides after 15 min of micro-aerobic shock. This provides not only a catalogue of oxidation-prone cysteine residues in the C. difficile proteome but also puts the amino acid cysteine into a key position in the oxidative stress response. Our study suggests that tolerance of C. difficile towards O
    • Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains.

      Premnath, Priyanka; Reck, Michael; Wittstein, Kathrin; Stadler, Marc; Wagner-Döbler, Irene; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2018-03-27)
      Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination. The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here. We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.
    • Worlds Apart - Transcriptome Profiles of Key Oral Microbes in the Periodontal Pocket Compared to Single Laboratory Culture Reflect Synergistic Interactions.

      Deng, Zhi-Luo; Sztajer, Helena; Jarek, Michael; Bhuju, Sabin; Wagner-Döbler, Irene; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Frontiers, 2018-02-06)
      Periodontitis is a worldwide prevalent oral disease which results from dysbiosis of the periodontal microbiome. Some of the most active microbial players, e.g., Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum, have extensively been studied in the laboratory, but it is unclear to which extend these findings can be transferred to in vivo conditions. Here we show that the transcriptional profiles of P. gingivalis, T. denticola, and F. nucleatum in the periodontal niche are distinct from those in single laboratory culture and exhibit functional similarities. GO (gene ontology) term enrichment analysis showed up-regulation of transporters, pathogenicity related traits and hemin/heme uptake mechanisms for all three species in vivo. Differential gene expression analysis revealed that cysteine proteases, transporters and hemin/heme-binding proteins were highly up-regulated in the periodontal niche, while genes involved in DNA modification were down-regulated. The data suggest strong interactions between those three species regarding protein degradation, iron up-take, and mobility in vivo, explaining their enhanced synergistic pathogenicity. We discovered a strikingly high frequency of Single Nucleotide Polymorphisms (SNPs) in vivo. For F. nucleatum we discovered a total of 127,729 SNPs in periodontal niche transcripts, which were found in similar frequency in health and disease and covered the entire genome, suggesting continuous evolution in the host. We conclude that metabolic interactions shape gene expression in vivo. Great caution is required when inferring pathogenicity of microbes from laboratory data, and microdiversity is an important adaptive trait of natural communities.
    • Packaging of Dinoroseobacter shibae DNA into Gene Transfer Agent Particles Is Not Random.

      Tomasch, Jürgen; Wang, Hui; Hall, April T K; Patzelt, Diana; Preusse, Matthias; Petersen, Jörn; Brinkmann, Henner; Bunk, Boyke; Bhuju, Sabin; Jarek, Michael; et al. (2018-01-01)
      Gene transfer agents (GTAs) are phage-like particles which contain a fragment of genomic DNA of the bacterial or archaeal producer and deliver this to a recipient cell. GTA gene clusters are present in the genomes of almost all marine Rhodobacteraceae (Roseobacters) and might be important contributors to horizontal gene transfer in the world's oceans. For all organisms studied so far, no obvious evidence of sequence specificity or other nonrandom process responsible for packaging genomic DNA into GTAs has been found. Here, we show that knock-out of an autoinducer synthase gene of Dinoroseobacter shibae resulted in overproduction and release of functional GTA particles (DsGTA). Next-generation sequencing of the 4.2-kb DNA fragments isolated from DsGTAs revealed that packaging was not random. DNA from low-GC conjugative plasmids but not from high-GC chromids was excluded from packaging. Seven chromosomal regions were strongly overrepresented in DNA isolated from DsGTA. These packaging peaks lacked identifiable conserved sequence motifs that might represent recognition sites for the GTA terminase complex. Low-GC regions of the chromosome, including the origin and terminus of replication, were underrepresented in DNA isolated from DsGTAs. DNA methylation reduced packaging frequency while the level of gene expression had no influence. Chromosomal regions found to be over- and underrepresented in DsGTA-DNA were regularly spaced. We propose that a "headful" type of packaging is initiated at the sites of coverage peaks and, after linearization of the chromosomal DNA, proceeds in both directions from the initiation site. GC-content, DNA-modifications, and chromatin structure might influence at which sides GTA packaging can be initiated.
    • The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.

      Fu, Chengzhang; Sikandar, Asfandyar; Donner, Jannik; Zaburannyi, Nestor; Herrmann, Jennifer; Reck, Michael; Wagner-Döbler, Irene; Koehnke, Jesko; Müller, Rolf; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124Braunschweig, Germany. (2017-11-16)
      The natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.
    • The Biofilm Inhibitor Carolacton Enters Gram-Negative Cells: Studies Using a TolC-Deficient Strain of Escherichia coli.

      Donner, Jannik; Reck, Michael; Bunk, Boyke; Jarek, Michael; App, Constantin Benjamin; Meier-Kolthoff, Jan P; Overmann, Jörg; Müller, Rolf; Kirschning, Andreas; Wagner-Döbler, Irene; et al. (2017-11-01)
      The myxobacterial secondary metabolite carolacton inhibits growth of Streptococcus pneumoniae and kills biofilm cells of the caries- and endocarditis-associated pathogen Streptococcus mutans at nanomolar concentrations. Here, we studied the response to carolacton of an Escherichia coli strain that lacked the outer membrane protein TolC. Whole-genome sequencing of the laboratory E. coli strain TolC revealed the integration of an insertion element, IS5, at the tolC locus and a close phylogenetic relationship to the ancient E. coli K-12. We demonstrated via transcriptome sequencing (RNA-seq) and determination of MIC values that carolacton penetrates the phospholipid bilayer of the Gram-negative cell envelope and inhibits growth of E. coli TolC at similar concentrations as for streptococci. This inhibition is completely lost for a C-9 (R) epimer of carolacton, a derivative with an inverted stereocenter at carbon atom 9 [(S) → (R)] as the sole difference from the native molecule, which is also inactive in S. pneumoniae and S. mutans, suggesting a specific interaction of native carolacton with a conserved cellular target present in bacterial phyla as distantly related as Firmicutes and Proteobacteria. The efflux pump inhibitor (EPI) phenylalanine arginine β-naphthylamide (PAβN), which specifically inhibits AcrAB-TolC, renders E. coli susceptible to carolacton. Our data indicate that carolacton has potential for use in antimicrobial chemotherapy against Gram-negative bacteria, as a single drug or in combination with EPIs. Strain E. coli TolC has been deposited at the DSMZ; together with the associated RNA-seq data and MIC values, it can be used as a reference during future screenings for novel bioactive compounds. IMPORTANCE The emergence of pathogens resistant against most or all of the antibiotics currently used in human therapy is a global threat, and therefore the search for antimicrobials with novel targets and modes of action is of utmost importance. The myxobacterial secondary metabolite carolacton had previously been shown to inhibit biofilm formation and growth of streptococci. Here, we investigated if carolacton could act against Gram-negative bacteria, which are difficult targets because of their double-layered cytoplasmic envelope. We found that the model organism Escherichia coli is susceptible to carolacton, similar to the Gram-positive Streptococcus pneumoniae, if its multidrug efflux system AcrAB-TolC is either inactivated genetically, by disruption of the tolC gene, or physiologically by coadministering an efflux pump inhibitor. A carolacton epimer that has a different steric configuration at carbon atom 9 is completely inactive, suggesting that carolacton may interact with the same molecular target in both Gram-positive and Gram-negative bacteria.
    • Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessary-clinical study and microbiota analysis.

      Gottschick, Cornelia; Deng, Zhi-Luo; Vital, Marius; Masur, Clarissa; Abels, Christoph; Pieper, Dietmar H; Rohde, Manfred; Mendling, Werner; Wagner-Döbler, Irene; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-13)
      Bacterial vaginosis (BV) is the most common vaginal syndrome among women in their reproductive years. It is associated with an increased risk of acquiring sexually transmitted infections and complications like preterm labor. BV is characterized by a high recurrence rate for which biofilms frequently found on vaginal epithelial cells may be a reason.
    • The urinary microbiota of men and women and its changes in women during bacterial vaginosis and antibiotic treatment.

      Gottschick, Cornelia; Deng, Zhi-Luo; Vital, Marius; Masur, Clarissa; Abels, Christoph; Pieper, Dietmar H; Wagner-Döbler, Irene; Helmholtz Centre for infection researchGmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-08-14)
      The urinary microbiota is similarly complex as the vaginal and penile microbiota, yet its role as a reservoir for pathogens and for recurrent polymicrobial biofilm diseases like bacterial vaginosis (BV) is not clear.
    • Use of Single-Frequency Impedance Spectroscopy to Characterize the Growth Dynamics of Biofilm Formation in Pseudomonas aeruginosa.

      van Duuren, Jozef B J H; Müsken, Mathias; Karge, Bianka; Tomasch, Jürgen; Wittmann, Christoph; Häussler, Susanne; Brönstrup, Mark (2017-07-12)
      Impedance spectroscopy has been applied in prokaryotic and eukaryotic cytometry as a label-free method for the investigation of adherent cells. In this paper, its use for characterizing the growth dynamics of P. aeruginosa biofilms is described and compared to crystal violet staining and confocal microscopy. The method allows monitoring the growth of biofilm-forming P. aeruginosa in a continuous and label-free manner over a period of 72 h in a 96 well plate format. Impedance curves obtained for P. aeruginosa PA14 wild type and mutant strains with a transposon insertion in pqsA and pelA genes exhibited distinct phases. We propose that the slope of the declining curve following a maximum at ca. 35-40 h is a measure of biofilm formation. Transplant experiments with P. aeruginosa biofilms and paraffin suggest that the impedance also reflects pellicle formation at the liquid-air interface, a barely considered contributor to impedance. Finally, the impairment of biofilm formation upon treatment of cultures with L-arginine and with ciprofloxacin, tobramycin and meropenem was studied by single frequency impedance spectroscopy. We suggest that these findings qualify impedance spectroscopy as an additional technique to characterize biofilm formation and its modulation by small molecule drugs.
    • Genomic Analysis of the Evolution of Phototrophy among Haloalkaliphilic Rhodobacterales.

      Kopejtka, Karel; Tomasch, Jürgen; Zeng, Yonghui; Tichý, Martin; Sorokin, Dimitry Y; Koblížek, Michal; Helmholtz Centre for infection research, Inhoffenstr.7,38124 Braunschweig, Germany. (2017-07-01)
      A characteristic feature of the order Rhodobacterales is the presence of a large number of photoautotrophic and photoheterotrophic species containing bacteriochlorophyll. Interestingly, these phototrophic species are phylogenetically mixed with chemotrophs. To better understand the origin of such variability, we sequenced the genomes of three closely related haloalkaliphilic species, differing in their phototrophic capacity and oxygen preference: the photoheterotrophic and facultatively anaerobic bacterium Rhodobaca barguzinensis, aerobic photoheterotroph Roseinatronobacter thiooxidans, and aerobic heterotrophic bacterium Natronohydrobacter thiooxidans. These three haloalcaliphilic species are phylogenetically related and share many common characteristics with the Rhodobacter species, forming together the Rhodobacter-Rhodobaca (RR) group. A comparative genomic analysis showed close homology of photosynthetic proteins and similarity in photosynthesis gene organization among the investigated phototrophic RR species. On the other hand, Rhodobaca barguzinensis and Roseinatronobacter thiooxidans lack an inorganic carbon fixation pathway and outer light-harvesting genes. This documents the reduction of their photosynthetic machinery towards a mostly photoheterotrophic lifestyle. Moreover, both phototrophic species contain 5-aminolevulinate synthase (encoded by the hemA gene) incorporated into their photosynthesis gene clusters, which seems to be a common feature of all aerobic anoxygenic phototrophic Alphaproteobacteria. Interestingly, the chrR-rpoE (sigma24) operon, which is part of singlet oxygen defense in phototrophic species, was found in the heterotrophic strain Natronohydrobacter thiooxidans. This suggests that this organism evolved from a photoheterotrophic ancestor through the loss of its photosynthesis genes. The overall evolution of phototrophy among the haloalkaliphilic members of the RR group is discussed.
    • Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host.

      Deng, Zhi-Luo; Szafrański, Szymon P; Jarek, Michael; Bhuju, Sabin; Wagner-Döbler, Irene; Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany. (2017-06-16)
      Periodontitis is an extremely prevalent disease worldwide and is driven by complex dysbiotic microbiota. Here we analyzed the transcriptional activity of the periodontal pocket microbiota from all domains of life as well as the human host in health and chronic periodontitis. Bacteria showed strong enrichment of 18 KEGG functional modules in chronic periodontitis, including bacterial chemotaxis, flagellar assembly, type III secretion system, type III CRISPR-Cas system, and two component system proteins. Upregulation of these functions was driven by the red-complex pathogens and candidate pathogens, e.g. Filifactor alocis, Prevotella intermedia, Fretibacterium fastidiosum and Selenomonas sputigena. Nine virulence factors were strongly up-regulated, among them the arginine deiminase arcA from Porphyromonas gingivalis and Mycoplasma arginini. Viruses and archaea accounted for about 0.1% and 0.22% of total putative mRNA reads, respectively, and a protozoan, Entamoeba gingivalis, was highly enriched in periodontitis. Fourteen human transcripts were enriched in periodontitis, including a gene for a ferric iron binding protein, indicating competition with the microbiota for iron, and genes associated with cancer, namely nucleolar phosphoprotein B23, ankyrin-repeat domain 30B-like protein and beta-enolase. The data provide evidence on the level of gene expression in vivo for the potentially severe impact of the dysbiotic microbiota on human health.
    • Sociodemographic determinants of spatial disparities in early childhood caries: An ecological analysis in Braunschweig, Germany.

      Meyer, Frederic; Karch, André; Schlinkmann, Kristin Maria; Dreesman, Johannes; Horn, Johannes; Rübsamen, Nicole; Sudradjat, Henny; Schubert, Rainer; Mikolajczyk, Rafael T; Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-05-26)
      To identify spatial disparities in dental caries experience (measured by dmft (decayed missing filled teeth) index) of children in the city of Braunschweig and to evaluate whether these disparities can be explained by sociodemographic characteristics.
    • Diversity and community composition of particle-associated and free-living bacteria in mesopelagic and bathypelagic Southern Ocean water masses: Evidence of dispersal limitation in the Bransfield Strait

      Milici, Mathias; Vital, Marius; Tomasch, Jürgen; Badewien, Thomas H.; Giebel, Helge A.; Plumeier, Iris; Wang, Hui; Pieper, Dietmar H.; Wagner-Döbler, Irene; Simon, Meinhard; et al. (Wiley-Blackwell, 2017-05-01)
      The Southern Ocean constitutes about 10% of the global oceans' volume and is characterized by high primary production. Particulate organic matter (POM) is exported from the photic zone to the deep ocean and sustains life of particle associated (PA) and free-living (FL) bacterial communities in the dark realm. Little is known about the composition and diversity of PA and FL bacterial communities below the photic zone and how they differ among various regions of the Southern Ocean. Therefore, we investigated the composition of small (3–8 μm) and large (> 8 μm) PA and FL (0.2–3 μm) bacterial communities between 500 m and 3600 m in the Bransfield Strait, Drake Passage, and the south Atlantic Ocean featuring also Southern Ocean water masses. PA bacterial communities had a higher OTU richness and evenness than FL ones. Taxonomic analysis revealed a different community composition between FL and PA bacteria. A large number of OTUs belonging to diverse phyla (Bacteroidetes, Planctomycetes, Betaproteobacteria, Deltaproteobacteria, and Verrucomicrobia) were significantly enriched on particles; in contrast very few bacterial lineages were FL specialists. Life-style (FL vs. PA) and region (Bransfield basin vs. other regions) strongly influenced bacterial communities. Depth explained only marginal fraction of the total variation (∼ 12%), suggesting that selective processes driven by depth have a smaller effect in the Southern Ocean when compared to life-style (25%) and region (31%). Overall these data indicate a strong influence of isolated water masses such as the basin of the Bransfield Strait on the composition of bacterial communities in the dark ocean. © 2017 The Authors Limnology and Oceanography published by Wiley Periodicals, Inc. on behalf of Association for the Sciences of Limnology and Oceanography
    • Dual function of tropodithietic acid as antibiotic and signaling molecule in global gene regulation of the probiotic bacterium Phaeobacter inhibens.

      Beyersmann, Paul G; Tomasch, Jürgen; Son, Kwangmin; Stocker, Roman; Göker, Markus; Wagner-Döbler, Irene; Simon, Meinhard; Brinkhoff, Thorsten; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-04-07)
      Antibiotics are typically regarded as microbial weapons, but whereas their function at concentrations lethal for bacteria is often well characterized, the role of antibiotics at much lower concentrations as possibly found under natural conditions remains poorly understood. By using whole-transcriptome analyses and phenotypic screenings of the marine bacterium Phaeobacter inhibens we found that the broad-spectrum antibiotic tropodithietic acid (TDA) causes the same regulatory effects in quorum sensing (QS) as the common signaling molecule N-acyl-homoserine lactone (AHL) at concentrations 100-fold lower than the minimal inhibitory concentration against bacteria. Our results show that TDA has a significant impact on the expression of ~10% of the total genes of P. inhibens, in the same manner as the AHL. Furthermore, TDA needs the AHL associated LuxR-type transcriptional regulator, just as the AHL molecule. Low concentrations of antibiotics can obviously have a strong influence on the global gene expression of the bacterium that produces it and drastically change the metabolism and behaviour of the bacterium. For P. inhibens this includes motility, biofilm formation and antibiotic production, all important for settlement on new host-associated surfaces. Our results demonstrate that bacteria can produce antibiotics not only to antagonise other bacteria, but also to mediate QS like endogenous AHL molecules.
    • Quorum sensing of Streptococcus mutans is activated by Aggregatibacter actinomycetemcomitans and by the periodontal microbiome.

      Szafrański, Szymon P; Deng, Zhi-Luo; Tomasch, Jürgen; Jarek, Michael; Bhuju, Sabin; Rohde, Manfred; Sztajer, Helena; Wagner-Döbler, Irene; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-03-20)
      The oral cavity is inhabited by complex microbial communities forming biofilms that can cause caries and periodontitis. Cell-cell communication might play an important role in modulating the physiologies of individual species, but evidence so far is limited.
    • Complete Genome Sequences of Three Multidrug-Resistant Clinical Isolates of Streptococcus pneumoniae Serotype 19A with Different Susceptibilities to the Myxobacterial Metabolite Carolacton.

      Donner, Jannik; Bunk, Boyke; Schober, Isabel; Spröer, Cathrin; Bergmann, Simone; Jarek, Michael; Overmann, Jörg; Wagner-Döbler, Irene; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-16)
      The full-genome sequences of three drug- and multidrug-resistant Streptococcus pneumoniae clinical isolates of serotype 19A were determined by PacBio single-molecule real-time sequencing, in combination with Illumina MiSeq sequencing. A comparison to the genomes of other pneumococci indicates a high nucleotide sequence identity to strains Hungary19A-6 and TCH8431/19A.