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  - Claus, Heike
A1  - Hubert, Kerstin
A1  - Becher, Dörte
A1  - Otto, Andreas
A1  - Pawlik, Marie-Christin
A1  - Lappann, Ines
A1  - Strobel, Lea
A1  - Vogel, Ulrich
A1  - Johswich, Kay
T1  - A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis
JF  - Scientific Reports
N2  - Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.
KW  - Meningitis
KW  - Pathogens
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200956
VL  - 9
ER  -