@article{GuptaSrivastavaOsmanogluetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Osmanoglu, {\"O}zge and Xu, Zhuofei and Brakhage, Axel A. and Dandekar, Thomas}, title = {Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {10}, issn = {2076-2607}, doi = {10.3390/microorganisms9102014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246318}, year = {2021}, abstract = {Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.}, language = {en} } @article{TabatabaiPrifertPfeiletal.2014, author = {Tabatabai, Julia and Prifert, Christiane and Pfeil, Johannes and Grulich-Henn, Juergen and Schnitzler, Paul}, title = {Novel Respiratory Syncytial Virus (RSV) Genotype ON1 Predominates in Germany during Winter Season 2012-13}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {10}, doi = {10.1371/journal.pone.0109191}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115229}, pages = {e109191}, year = {2014}, abstract = {Respiratory syncytial virus (RSV) is the leading cause of hospitalization especially in young children with respiratory tract infections (RTI). Patterns of circulating RSV genotypes can provide a better understanding of the molecular epidemiology of RSV infection. We retrospectively analyzed the genetic diversity of RSV infection in hospitalized children with acute RTI admitted to University Hospital Heidelberg/Germany between October 2012 and April 2013. Nasopharyngeal aspirates (NPA) were routinely obtained in 240 children younger than 2 years of age who presented with clinical symptoms of upper or lower RTI. We analyzed NPAs via PCR and sequence analysis of the second variable region of the RSV G gene coding for the attachment glycoprotein. We obtained medical records reviewing routine clinical data. RSV was detected in 134/240 children. In RSV-positive patients the most common diagnosis was bronchitis/bronchiolitis (75.4\%). The mean duration of hospitalization was longer in RSV-positive compared to RSV-negative patients (3.5 vs. 5.1 days; p < 0.01). RSV-A was detected in 82.1\%, RSV-B in 17.9\% of all samples. Phylogenetic analysis of 112 isolates revealed that the majority of RSV-A strains (65\%) belonged to the novel ON1 genotype containing a 72-nucleotide duplication. However, genotype ON1 was not associated with a more severe course of illness when taking basic clinical/laboratory parameters into account. Molecular characterization of RSV confirms the co-circulation of multiple genotypes of subtype RSV-A and RSV-B. The duplication in the G gene of genotype ON1 might have an effect on the rapid spread of this emerging RSV strain.}, language = {en} } @article{HentschelKamkeRinkeetal.2014, author = {Hentschel, Ute and Kamke, Janine and Rinke, Christian and Schwientek, Patrick and Mavromatis, Kostas Mavromatis and Ivanova, Natalia and Sczyrba, Alexander and Woyke, Tanja}, title = {The Candidate Phylum Poribacteria by Single-Cell Genomics: New Insights into Phylogeny, Cell-Compartmentation, Eukaryote-Like Repeat Proteins, and Other Genomic Features}, doi = {10.1371/journal.pone.0087353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112649}, year = {2014}, abstract = {The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake.}, language = {en} } @phdthesis{Tabares2011, author = {Tabares, Paula}, title = {Antimicrobial, anti-protease and immunomodulatory activities of secondary metabolites from Caribbean sponges and their associated bacteria}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67000}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Marine sponges and their associated bacteria have been proven to be a rich source of novel secondary metabolites with therapeutic usefulness in infection and autoimmunity. This Ph.D. project aimed to isolate bioactive secondary metabolites from the marine sponges Amphimedon compressa, Aiolochroia crassa and Theonella swinhoei as well as from bacteria associated with different Caribbean sponges, specifically actinomycetes and sphingomonads. In this study, amphitoxin was isolated from the crude methanol extract of the sponge A. compressa and it was found to have antibacterial and anti-parasitic activities. Amphitoxin showed protease inhibitory activity when tested against the mammalian protease cathepsin B and the parasitic proteases rhodesain and falcipain-2. Furthermore, miraziridine A was identified in the dichloromethane extract of the sponge T. swinhoei collected offshore Israel in the Red Sea. Miraziridine A, a natural peptide isolated previously from the marine sponge Theonella aff. mirabilis, is a potent cathepsin B inhibitor with an IC50 value of 1.4 g/mL (2.1 M). Secondary metabolites from sponge-derived bacteria were also isolated and identified. A total of 79 strains belonging to 20 genera of the order Actinomycetales and seven strains belonging to two genera of the order Sphingomonadales were cultivated from 18 different Caribbean sponges and identified by 16S rRNA gene sequencing. Seven of these strains are likely to represent novel species. Crude extracts from selected strains were found to exhibit protease inhibition against cathepsins B and L, rhodesain, and falcipain-2 as well as immunomodulatory activities such as induction of cytokine release by human peripheral blood mononuclear cells. The isolates Sphingobium sp. CO105 and Lapillicoccus sp. BA53 were selected for cultivation, extraction and purification of bioactive metabolites based on initial bioactive screening results. The isoalloxazine isolumichrome was isolated from the strain Sphingobium sp. CO105 which inhibited the protease rhodesain with an IC50 of 0.2 M. The strain Lapillicoccus sp. BA53 was found to produce p-aminosalicylic acid methyl ester, which showed activity against the proteases cathepsins B and L, falcipain-2 and rhodesain. These results highlight the significance of marine sponge-associated bacteria to produce bioactive secondary metabolites with therapeutic potential in the treatment of infectious diseases and disorders of the immune system.}, subject = {Schw{\"a}mme}, language = {en} } @phdthesis{Muench2006, author = {M{\"u}nch, Julia Eva Maria}, title = {Nachweis von Rekombination innerhalb des Norovirus-Capsidgens}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28789}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Diese Arbeit zeigt das Vorkommen von f{\"u}nfundzwanzig neuen Norovirusst{\"a}mmen in Deutschland und stellt ihre phylogenetischen Verwandschaftsverh{\"a}ltnisse dar. Bei zweien dieser St{\"a}mme handelte es sich um nat{\"u}rlich entstandene rekombinante Viren, deren Rekombinationsbruchpunkte innerhalb der Capsidregion lagen. Die Schnittstellen wiesen in ihrer unmittelbaren Umgebung charakteristische Eigenschaften rekombinanter Viren auf. Die Virulenz und die Antigenit{\"a}t des Erregers, sowie die Methoden der taxonomischen Zuordnung wurden in Bezug auf die Tragweite dieser Ergebnisse diskutiert. Die genetische Information f{\"u}r den Virusnachweis wurde aus 119 NV-positiven Stuhlproben von bis zu vier Jahre alten Kindern isoliert und sind in den St{\"a}dten Hamburg, Bochum, Freiburg, Erlangen und Dresden zwischen 1997 und 1998 gesammelt worden. Durch Amplifikation und Sequenzierung wurde die komplette Capsidsequenz von f{\"u}nfundzwanzig zuvor noch nicht beschriebenen NV-St{\"a}mmen ermittelt und mit Maximum-Likelihood Analysen ihre verwandschaftliche Beziehung als phylogenetischer Baum dargestellt. Durch verschiedene, zum Rekombinationsnachweis geeignete Methoden (Exploratory Tree Analysis, Similarity Plots, Splits Tree und Sawyer´s Test) wurden der Datensatz auf das Vorkommen von Rekombinationsereignissen untersucht. Splits Tree lieferte zun{\"a}chst Hinweise auf insgesamt drei rekombinante St{\"a}mme: Hamburg180/1997/GE (HH180), Hamburg137/1997/GE (HH137) und Bochum272/1987/GE (BO272). Durch die im Anschluss verwendeten Methoden (s. o.) wurden jedoch nur die zwei Erstgenannten als Mosaiksequenzen best{\"a}tigt, so dass der Stamm BO272 nicht in die Endergebnisse aufgenommen wurde. Sim Plot und Exploratory Tree Analysis ordneten den rekombinanten St{\"a}mmen die jeweiligen Parentalst{\"a}mme zu. Dem zufolge entstanden beide Rekombinanten aus Viren der NV-Genogruppe II/4, HH180 aus Hamburg189/1997/GE und Bochum024/1998/GE und HH137 aus Hamburg189/1997/GE und Hamburg139/1997/GE. Durch das Programm LARD wurden die genauen Lokalisationen der jeweiligen Rekombinationsbruchpunkte ermittelt. Diese befanden sich beim Stamm HH180 an den Sequenzpositionen 519 nt und 762 nt und beim Stamm HH137 an der Position 768 nt. Vor und nach diesen Bruchpunkten wurden Maximum-Likelihood-B{\"a}ume aus dem rekombinantem Stamm, den beiden Parentalst{\"a}mmen und einer Außengruppe erstellt. Mit hohen Boostrapwerten f{\"u}r die einzelnen Verzweigungen wechselten beide rekombinanten St{\"a}mme nach jedem Bruchpunkt ihre phylogenetische Zugeh{\"o}rigkeit zu einem anderen Parentalvirus innerhalb des konstruierten Baumes. Um beurteilen zu k{\"o}nnen, ob Noroviren generell dazu neigen, genetische Information auszutauschen, wurde die Struktur der Rekombinationsregion anaysiert und mit der Struktur von Viren, bei denen Rekombinationsereignisse geh{\"a}uft nachgewiesen werden konnten, verglichen. Beide St{\"a}mmme zeigten typische Eigenschaften von sogenannten ‚homologous recombination activators'. In Bezug auf die Genomorganisation befanden sich bei jeder Rekombinanten eine der Schnittstellen im Bereich der Protruding-Region der Capsidsequenz, in der sich vermutlich die Antik{\"o}rper-Bindungsstelle des Virus befindet. Diese Studie zeigt also im Einklang mit sp{\"a}teren Ergebnissen, dass homologe Rekombination innerhalb des NV-Capsidgens kein isoliertes Ereignis darstellt. Im Hinblick auf immunologische Bedeutung und Klassifikation wurde die Tragweite von Rekombinationsereignissen innerhalb verschiedener Genomabschnitten diskutiert und alternative L{\"o}sungen vorgeschlagen. Es ist fraglich, ob bei nat{\"u}rlichem Vorkommen von Rekombination in wahrscheinlich immunologisch bedeutsamen Regionen des Virusgenoms die Sequenzierung der Polymerase-Region zur Klassifikation ausreicht, oder ob die Verwendung der Capsidregion sinnvoller w{\"a}re.}, subject = {Homologe Rekombination}, language = {de} }