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Wiehlmann L.,Klinische Forschergruppe | Cramer N.,Klinische Forschergruppe | Ulrich J.,Institute For Medizinische Mikrobiologie Und Krankenhaushygiene | Hedtfeld S.,Klinische Forschergruppe | And 2 more authors.
International Journal of Medical Microbiology | Year: 2012

Pseudomonas aeruginosa is the major pathogen in chronic lung infections of individuals with cystic fibrosis (CF). Unrelated CF patients may acquire . P. aeruginosa from the environment or by cross-infection in the CF setting. We tested the efficacy of measures to prevent nosocomial acquisition of . P. aeruginosa at a Paediatric CF centre in a prospective 10-year study. . P. aeruginosa-positive and . P. aeruginosa-negative patients were seen in alternating weeks at the outpatient clinic. Faucets were equipped with filters to prevent bacterial contamination of tap water. Serial isolates were collected since the first documentation of a . P. aeruginosa-positive culture and genotyped with a multimarker microarray. During the 10-year study, the annual prevalence of patients with at least one . P. aeruginosa-positive culture was 39. ±. 6% in a population of 149. ±. 12 patients. . P. aeruginosa was detected for the first time in 54 patients of whom 11 patients became chronically colonised with . P. aeruginosa. Transient colonisations were recorded 97 times. A nosocomial acquisition of . P. aeruginosa at the CF centre probably happened in one case. The worldwide dominant clones in the global . P. aeruginosa population were also the most abundant clones in the panel of 324 early CF isolates. No rare clone had expanded by nosocomial transmission. It can be concluded that cross-infection with . P. aeruginosa was prevented with simple hygienic measures at a CF centre that had experienced local outbreaks of nosocomial spread among unrelated patients in the past. © 2011 Elsevier GmbH.


Mainz J.G.,Jena University Hospital | Hentschel J.,Jena University Hospital | Schien C.,Jena University Hospital | Cramer N.,Klinische Forschergruppe | And 3 more authors.
Journal of Cystic Fibrosis | Year: 2012

We report on two CF patients who received double lung transplantation (LTX) due to Pseudomonas aeruginosa related pulmonary destruction. Prior to LTX we detected P. aeruginosa in nasal lavages (NL) and sputum cultures from both patients. Donor lungs of patient 1 became colonized within four weeks with P. aeruginosa identical in genotype with isolates from his pre-transplant sputum cultures and pre- and post-transplant NL.In contrast, patient 2 remained P. aeruginosa free in lower airway samples (bronchial lavage/sputum) for now up to 30. months, despite persistent detection of P. aeruginosa that was identical in genotype with pre-transplant NL and sputum isolates in NL and even in throat swabs. For prevention of pulmonary re-colonization patient 2 has continuously inhaled Colomycin 1. MIU once daily during the preceding more than 36 months with the novel Pari Sinus™ nebulizer, which in scintigraphic studies was shown to deliver vibrating aerosols into paranasal sinuses, additional to bronchial antibiotic inhalation. Discussion: Pulmonary colonization of transplanted donor lungs with identical clones previously colonizing the explanted lungs has been described previously and the upper airways were postulated as reservoir for descending colonization. However, this remained speculative, as upper airway sampling which does not belong to current standards, was not performed in these studies.Our report demonstrates persistence of identical P. aeruginosa genotypes in CF upper airways prior to and after LTX underlining risks of descending colonization of transplanted lungs with P. aeruginosa, which increases risks of graft dysfunction. Therefore, we recommend regular assessment of sinonasal colonization prior to and after LTX. Sinonasal inhalation with antimicrobials should be investigated in prospective trials. © 2011 European Cystic Fibrosis Society.


Melchers I.,Klinische Forschergruppe
Zeitschrift fur Rheumatologie | Year: 2011

Genetic risk factors are known to exist for all collagen vascular diseases. They are most important for systemic lupus erythematosus (SLE) and systemic scleroderma (SSc), as shown by the systematic analysis of family data. Both diseases to date share most of the validated risk factors (PTPN22, STAT4, BANK1, TNFAIP3, IRF5, BLK) underlining once again their relationship. Moreover, most of these factors were also shown to be associated with other autoimmune diseases. Many additional risk factors exist, but need further analysis. The HLA complex is of special interest, as many loci within this region, some highly polymorphic, may contribute to the total genetic risk. © Springer-Verlag 2011.


Davenport C.,Klinische Forschergruppe | Ussery D.W.,Technical University of Denmark | Tummler B.,Klinische Forschergruppe
Photosynthesis Research | Year: 2010

Eleven completely sequenced Chlorobi genomes were compared in oligonucleotide usage, gene contents, and synteny. The green sulfur bacteria (GSB) are equipped with a core genome that sustains their anoxygenic phototrophic lifestyle by photosynthesis, sulfur oxidation, and CO2 fixation. Whole-genome gene family and single gene sequence comparisons yielded similar phylogenetic trees of the sequenced chromosomes indicating a concerted vertical evolution of large gene sets. Chromosomal synteny of genes is not preserved in the phylum Chlorobi. The accessory genome is characterized by anomalous oligonucleotide usage and endows the strains with individual features for transport, secretion, cell wall, extracellular constituents, and a few elements of the biosynthetic apparatus. Giant genes are a peculiar feature of the genera Chlorobium and Prosthecochloris. The predicted proteins have a huge molecular weight of 106, and are probably instrumental for the bacteria to generate their own intimate (micro)environment. © 2010 Springer Science+Business Media B.V.


Cramer N.,Klinische Forschergruppe | Klockgether J.,Klinische Forschergruppe | Wrasman K.,Klinische Forschergruppe | Schmidt M.,Klinische Forschergruppe | And 2 more authors.
Environmental Microbiology | Year: 2011

Clones C and PA14 are the worldwide most abundant clonal complexes in the Pseudomonas aeruginosa population. The microevolution of clones C and PA14 was investigated in serial cystic fibrosis (CF) airway isolates collected over 20 years since the onset of colonization. Intraclonal evolution in CF lungs was resolved by genome sequencing of first, intermediate and late isolates and subsequent multimarker SNP genotyping of the whole strain panel. Mapping of sequence reads onto the P. aeruginosa PA14 reference genome unravelled an intraclonal and interclonal sequence diversity of 0.0035% and 0.68% respectively. Clone PA14 diversified into three branches in the patient's lungs, and the PA14 population acquired 15 nucleotide substitutions and a large deletion during the observation period. The clone C genome remained invariant during the first 3 years in CF lungs; however, 15 years later 947 transitions and 12 transversions were detected in a clone C mutL mutant strain. Key mutations occurred in retS, RNA polymerase, multidrug transporter, virulence and denitrification genes. Late clone C and PA14 persistors in the CF lungs were compromised in growth and cytotoxicity, but their mutation frequency was normal even in mutL mutant clades. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.


Frimmersdorf E.,TU Braunschweig | Horatzek S.,Klinische Forschergruppe | Pelnikevich A.,Klinische Forschergruppe | Wiehlmann L.,Klinische Forschergruppe | Schomburg D.,TU Braunschweig
Environmental Microbiology | Year: 2010

In addition to transcriptome and proteome studies, metabolome analysis represents a third complementary approach to identify metabolic pathways and adaptation processes. In order to elucidate basic principles of metabolic versatility of Pseudomonas aeruginosa, we investigated the metabolome profiles of two genetically and morphologically divergent strains, the reference strain PAO1 and the mucoid clinical isolate TBCF10839 in exponential growth and stationary phase in six different carbon sources (cadaverine, casamino acids, citrate, glucose, succinate and tryptone). Both strains exhibited strong similarities in mode of growth; the metabolite patterns were mainly defined by the growth condition. Besides this adaptive response, a basic core metabolism shapes the P. aeruginosa metabolome, independent of growth phase, carbon source and genetic background. This core metabolism includes pathways related to the central energy and amino acid metabolism. These consistently utilized metabolic pathways are closely related to glutamate which represents a dominant metabolite in all conditions analysed. In nutrient-depleted media of stationary phase cultures, P. aeruginosa maintains a specific repertoire of metabolic pathways that are related to the carbon source formerly available. This specified adaptation strategy combined with the invariant basic core metabolism may represent a fundamental requirement for the metabolic versatility of this organism. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.


Davenport C.F.,Klinische Forschergruppe | Tummler B.,Klinische Forschergruppe
Environmental Microbiology | Year: 2013

Second-generation sequencing technologies are revolutionizing the study of metagenomes. Whole-genome shotgun sequencing of metagenomic DNA may become an attractive alternative to the current widely used ribosomal RNA gene studies. Large data sets of short sequence reads are mapped onto a custom microbial reference sequence. If a bacterial pangenome of completely sequenced genomes is taken as a reference, the output consists of the distribution of bacterial taxa in and bacterial gene contents of the metagenome. The relative abundance of functional categories and of individual pathways and fitness traits encoded by the metagenomic gene pool provides insight into habitat-specific features of the microbial community. Polymorphic sites in sequence reads may resolve the number and abundance of individual clonal complexes of dominant species in the polymicrobial community. These SNPs and de novo mutations may be exploited to trace the spatiotemporal spread of clones and the emergence of novel traits such as fitness or resistance determinants. In conclusion, massively parallel sequencing of metagenomic DNA allows deep insights into the composition and the genetic repertoire of polymicrobial communities. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.


Bals R.,Universitatsklinikum des Saarlandes | Hubert D.,CRCM Service de Pneumologie Hopital Cochin | Tummler B.,Klinische Forschergruppe
Journal of Cystic Fibrosis | Year: 2011

Chronic infection of the respiratory tract is a hallmark of cystic fibrosis (CF). Antibiotic treatment has been used as one of the mainstays of therapy and together with other treatment modalities has resulted in increased survival of CF patients. Increasing resistance of CF-specific pathogens to various classes of antibiotics explains the need for novel antibiotic strategies. This review focuses on the future development of new antibiotic therapies, including: (1) New targets, (2) novel antibiotic regimens in CF, (3) new antibiotics, and (4) other investigational therapies. In addition, we briefly summarize developments in the area of microbial diagnostics and discuss interactions between the complex pulmonary microflora. © 2011 European Cystic Fibrosis Society.


Selezska K.,Helmholtz Center for Infection Research | Kazmierczak M.,Leibniz Institute DSMZ German Collection of Microorganisms and Cell Cultures | Musken M.,Center for Experimental and Clinical Infection Research | Garbe J.,Lund University | And 6 more authors.
Environmental Microbiology | Year: 2012

Pseudomonas aeruginosa attracts research attention as a common opportunistic nosocomial pathogen causing severe health problems in humans. Nevertheless, its primary habitat is the natural environment. Here, we relate the genetic diversity of 381 environmental isolates from rivers in northern Germany to ecological factors such as river system, season of sampling and different levels of water quality. From representatives of 99 environmental clones, also in comparison with 91 clinical isolates, we determined motility phenotypes, virulence factors, biofilm formation, serotype and the resistance to seven environmental P. aeruginosa phages. The integration of genetic, ecological and phenotypic data showed (i) the presence of several extended clonal complexes (ecc) which are non-uniformly distributed across different water qualities, and (ii) a correlation of the hosts' serotype composition with susceptibility towards distinct groups of environmental phages. For at least one ecc (eccB), we assumed the ecophysiological differences on environmental water adaptation and phage resistance to be so distinct as to reinforce an environmentally driven cladogenic split from the remainder of P. aeruginosa. In summary, we conclude that the majority of the microevolutionary population dynamics of P. aeruginosa were shaped by the natural environment and not by the clinical habitat. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.


Tummler B.,Klinische Forschergruppe | Wiehlmann L.,Klinische Forschergruppe | Klockgether J.,Klinische Forschergruppe | Cramer N.,Klinische Forschergruppe
F1000Prime Reports | Year: 2014

Pseudomonas aeruginosa, the type species of pseudomonads, is an opportunistic pathogen that colonizes a wide range of niches. Current genome sequencing projects are producing previously inconceivable detail about the population biology and evolution of P. aeruginosa. Its pan-genome has a larger genetic repertoire than the human genome, which explains the broad metabolic capabilities of P. aeruginosa and its ubiquitous distribution in aquatic habitats. P. aeruginosa may persist in the airways of individuals with cystic fibrosis for decades. The ongoing whole-genome analyses of serial isolates from cystic fibrosis patients provide the so far singular opportunity to monitor the microevolution of a bacterial pathogen during chronic infection over thousands of generations. Although the evolution in cystic fibrosis lungs is neutral overall, some pathoadaptive mutations are selected during the within-host evolutionary process. Even a single mutation may be sufficient to generate novel complex traits provided that predisposing mutational events have previously occurred in the clonal lineage. © 2014 Faculty of 1000 Ltd.

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