TY  - JOUR
A1  - Taha, Muhamed-Kheir
A1  - Claus, Heike
A1  - Lappann, Martin
A1  - Veyrier, Frédéric J.
A1  - Otto, Andreas
A1  - Becher, Dörte
A1  - Deghmane, Ala-Eddine
A1  - Frosch, Matthias
A1  - Hellenbrand, Wiebke
A1  - Hong, Eva
A1  - du Châtelet, Isabelle Parent
A1  - Prior, Karola
A1  - Harmsen, Dag
A1  - Vogel, Ulrich
T1  - Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men
JF  - PLoS ONE
N2  - 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.
KW  - nitrites
KW  - genome sequencing
KW  - men who have sex with men
KW  - meningococcal disease
KW  - Neisseria meningitidis
KW  - Neisseria gonorrhoeae
KW  - mammalian genomics
KW  - mouse models
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179870
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Biju, Joseph
A1  - Schwarz, Roland
A1  - Linke, Burkhard
A1  - Blom, Jochen
A1  - Becker, Anke
A1  - Claus, Heike
A1  - Goesmann, Alexander
A1  - Frosch, Matthias
A1  - Müller, Tobias
A1  - Vogel, Ulrich
A1  - Schoen, Christoph
T1  - Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome
JF  - PLoS One
N2  - 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.
KW  - population genetics
KW  - DNA recombination
KW  - meningococcal disease
KW  - recombinant proteins
KW  - genomic databases
KW  - comparative genomics
KW  - neisseria meningitidis
KW  - homologous recombination
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137960
VL  - 6
IS  - 4
ER  -