@article{BijuSchwarzLinkeetal.2011,
  author    = {Biju, Joseph and Schwarz, Roland and Linke, Burkhard and Blom, Jochen and Becker, Anke and Claus, Heike and Goesmann, Alexander and Frosch, Matthias and M{\"u}ller, Tobias and Vogel, Ulrich and Schoen, Christoph},
  title     = {Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {4},
  doi       = {10.1371/journal.pone.0018441},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137960},
  pages     = {e18441},
  year      = {2011},
  abstract  = {Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40\% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.},
  language  = {en}
}
@article{HubertPawlikClausetal.2012,
  author    = {Hubert, Kerstin and Pawlik, Marie-Christin and Claus, Heike and Jarva, Hanna and Meri, Seppo and Vogel, Ulrich},
  title     = {Opc Expression, LPS Immunotype Switch and Pilin Conversion Contribute to Serum Resistance of Unencapsulated Meningococci},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0045132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135421},
  pages     = {e45132},
  year      = {2012},
  abstract  = {Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST)-41/44 clonal complex (cc) strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp) and MutS, a protein of the DNA repair mechanism. After killing of >99.9\% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS) immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens.},
  language  = {en}
}
@article{SchwerkPapandreouSchuhmannetal.2012,
  author    = {Schwerk, Christian and Papandreou, Thalia and Schuhmann, Daniel and Nickol, Laura and Borkowski, Julia and Steinmann, Ulrike and Quednau, Natascha and Stump, Carolin and Weiss, Christel and Berger, J{\"u}rgen and Wolburg, Hartwig and Claus, Heike and Vogel, Ulrich and Ishikawa, Hiroshi and Tenenbaum, Tobias and Schroten, Horst},
  title     = {Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0030069},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131459},
  pages     = {e30069},
  year      = {2012},
  abstract  = {Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.},
  language  = {en}
}
@article{MoremiMshanaKamugishaetal.2012,
  author    = {Moremi, Nyambura and Mshana, Stephen E. and Kamugisha, Erasmus and Kataraihya, Johannes B. and Tappe, Dennis and Vogel, Ulrich and Lyamuya, Eligius F. and Claus, Heike},
  title     = {Predominance of methicillin resistant Staphylococcus aureus-ST88 and new ST1797 causing wound infection and abscesses},
  series = {Journal of Infection in Developing Countries},
  volume    = {6},
  journal   = {Journal of Infection in Developing Countries},
  number    = {8},
  doi       = {10.3855/jidc.2093},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134746},
  pages     = {620-625},
  year      = {2012},
  abstract  = {Introduction: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. Methodology: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15\%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Results: Despite considerable genetic diversity, the spa types t690 (29.1\%) and t7231 (41.6\%), as well as the sequence types (ST) 88 (54.2\%) and 1797 (29.1\%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8\%, 62.5\%, 41.6\%, 45.8\% and 50\% of the strains, respectively. Conclusion: We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures.},
  language  = {en}
}
@article{HarrisonClausJiangetal.2013,
  author    = {Harrison, Odile B. and Claus, Heike and Jiang, Ying and Bennett, Julia S. and Bratcher, Holly B. and Jolley, Keith A. and Corton, Craig and Care, Rory and Poolman, Jan T. and Zollinger, Wendell D. and Frasch, Carl E. and Stephens, David S. and Feavers, Ian and Frosch, Matthias and Parkhill, Julian and Vogel, Ulrich and Quail, Michael A. and Bentley, Stephen D. and Maiden, Martin C. J.},
  title     = {Description and Nomenclature of Neisseria meningitidis Capsule Locus},
  series = {Emerging Infectious Diseases},
  volume    = {19},
  journal   = {Emerging Infectious Diseases},
  number    = {4},
  doi       = {10.3201/eid1904.111799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131703},
  pages     = {566-573},
  year      = {2013},
  abstract  = {Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.},
  language  = {en}
}
@article{BrehonyTrotterRamsayetal.2014,
  author    = {Brehony, Carina and Trotter, Caronline L. and Ramsay, Mary E. and Chandra, Manosree and Jolley, Keith A. and van der Ende, Arie and Carion, Fran{\c{c}}oise and Berthelsen, Lene and Hoffmann, Steen and Harðard{\´o}ttir, Hj{\"o}rd{\´i}s and Vazques, Julio A. and Murphy, Karen and Toropainen, Maija and Cani{\c{c}}a, Manuela and Ferreira, Eugenia and Diggle, Mathew and Edwards, Giles F. and Taha, Muhamed-Kheir and Stefanelli, Paola and Kriz, Paula and Gray, Steve J. and Fox, Andrew J. and Jacobsson, Susanne and Claus, Heike and Vogel, Ulrich and Tzanakaki, Georgina and Heuberger, Sigrid and Caugant, Dominique A. and Frosch, Matthias and Maiden, Martin C. J.},
  title     = {Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development},
  series = {Clinical and Vaccine Immunology : CVI},
  volume    = {21},
  journal   = {Clinical and Vaccine Immunology : CVI},
  number    = {6},
  doi       = {10.1128/cvi.00133-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120808},
  pages     = {847-53},
  year      = {2014},
  abstract  = {New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.},
  language  = {en}
}
@article{TahaClausLappannetal.2016,
  author    = {Taha, Muhamed-Kheir and Claus, Heike and Lappann, Martin and Veyrier, Fr{\´e}d{\´e}ric J. and Otto, Andreas and Becher, D{\"o}rte and Deghmane, Ala-Eddine and Frosch, Matthias and Hellenbrand, Wiebke and Hong, Eva and du Ch{\^a}telet, Isabelle Parent and Prior, Karola and Harmsen, Dag and Vogel, Ulrich},
  title     = {Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0154047},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179870},
  year      = {2016},
  abstract  = {Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.},
  language  = {en}
}
@article{MoremiClausMshana2016,
  author    = {Moremi, Nyambura and Claus, Heike and Mshana, Stephen E.},
  title     = {Antimicrobial resistance pattern: a report of microbiological cultures at a tertiary hospital in Tanzania},
  series = {BMC Infectious Diseases},
  volume    = {16},
  journal   = {BMC Infectious Diseases},
  number    = {756},
  doi       = {10.1186/s12879-016-2082-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161185},
  year      = {2016},
  abstract  = {Background Antimicrobial resistance has been declared by the World Health Organization as a threat to the public health. The aim of this study was to analyze antimicrobial resistance patterns of the common pathogens occurring at the Bugando Medical Centre (BMC), Mwanza, Tanzania to provide data for antimicrobial stewardship programmes. Methods A total of 3330 microbiological culture results scripts representing non-repetitive specimens reported between June 2013 and May 2015 were retrieved and analyzed for pathogens and their susceptibility patterns using STATA-11 software. Results Out of 3330 specimens, 439 (13.2\%) had positive culture. Staphylococcus aureus (n = 100; 22.8\%), Klebsiella pneumoniae (n = 65; 14.8\%) and Escherichia coli (n = 41; 9.3\%) were the most frequently isolated bacteria. Of 78 Staphylococcus aureus tested, 27 (34.6\%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Rates of resistance of Klebsiella pneumoniae and Escherichia coli isolates to third generation cephalosporins were 38.5\% (25/65) and 29.3\% (12/41) respectively. Staphylococcus aureus and Klesbiella pneumoniae were commonly isolated from bloodstream infections while Escherichia coli and Pseudomonas aeruginosa were the predominant isolates from urinary tract and wounds infections respectively. Of 23 Salmonella species isolated, 22 (95\%) were recovered from the blood. Nine of the 23 Salmonella species isolates (39\%) were found to be resistant to third generation cephalosporins. The resistance rate of gram-negative bacteria to third generation cephalosporins increased from 26.5\% in 2014 to 57.9\% in 2015 (p = 0.004) while the rate of MRSA decreased from 41.2\% in 2013 to 9.5\% in 2015 (p = 0.016). Multidrug-resistant gram-negative isolates were commonly isolated from Intensive Care Units and it was noted that, the majority of invasive infections were due to gram-negative bacteria. Conclusion There is an increase in proportion of gram-negative isolates resistant to third generation cephalosporins. The diversity of potential pathogens resistant to commonly prescribed antibiotics underscores the importance of sustained and standardized antimicrobial resistance surveillance and antibiotic stewardship programmes in developing countries.},
  language  = {en}
}
@article{HellenbrandClausSchinketal.2016,
  author    = {Hellenbrand, Wiebke and Claus, Heike and Schink, Susanne and Marcus, Ulrich and Wichmann, Ole and Vogel, Ulrich},
  title     = {Risk of Invasive Meningococcal Disease in Men Who Have Sex with Men: Lessons Learned from an Outbreak in Germany, 2012-2013},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0160126},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166842},
  pages     = {e0160126},
  year      = {2016},
  abstract  = {Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012-2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002-2014. Results Among the 148 IMD-cases notified from 01.01.2012-30.09.2013 in 18-59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5-1,10-8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5-1,10-8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002-2014 was lacking, clusters were more frequent in men aged 20-49 years. Molecular analysis of C:P1.5-1,10-8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control.},
  language  = {en}
}
@article{MoremiClausVogeletal.2017,
  author    = {Moremi, Nyambura and Claus, Heike and Vogel, Ulrich and Mshana, Stephen E.},
  title     = {Surveillance of surgical site infections by Pseudomonas aeruginosa and strain characterization in Tanzanian hospitals does not provide proof for a role of hospital water plumbing systems in transmission},
  series = {Antimicrobial Resistance and Infection Control},
  volume    = {6},
  journal   = {Antimicrobial Resistance and Infection Control},
  number    = {56},
  doi       = {10.1186/s13756-017-0216-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158168},
  year      = {2017},
  abstract  = {Background The role of hospital water systems in the development of Pseudomonas aeruginosa (P. aeruginosa) surgical site infections (SSIs) in low-income countries is barely studied. This study characterized P. aeruginosa isolates from patients and water in order to establish possible epidemiological links. Methods: Between December 2014 and September 2015, rectal and wound swabs, and water samples were collected in the frame of active surveillance for SSIs in the two Tanzanian hospitals. Typing of P. aeruginosa was done by multi-locus sequence typing. Results: Of 930 enrolled patients, 536 were followed up, of whom 78 (14.6\%, 95\% CI; 11.6-17.5) developed SSIs. P. aeruginosa was found in eight (14\%) of 57 investigated wounds. Of the 43 water sampling points, 29 were positive for P. aeruginosa. However, epidemiological links to wound infections were not confirmed. The P. aeruginosa carriage rate on admission was 0.9\% (8/930). Of the 363 patients re-screened upon discharge, four (1.1\%) possibly acquired P. aeruginosa during hospitalization. Wound infections of the three of the eight P. aeruginosa SSIs were caused by a strain of the same sequence type (ST) as the one from intestinal carriage. Isolates from patients were more resistant to antibiotics than water isolates. Conclusions: The P. aeruginosa SSI rate was low. There was no evidence for transmission from tap water. Not all P. aeruginosa SSI were proven to be endogenous, pointing to other routes of transmission.},
  language  = {en}
}