TY  - JOUR
A1  - Doran, Kelly S.
A1  - Fulde, Marcus
A1  - Gratz, Nina
A1  - Kim, Brandon J.
A1  - Nau, Roland
A1  - Prasadarao, Nemani
A1  - Schubert-Unkmeir, Alexandra
A1  - Tuomanen, Elaine I.
A1  - Valentin-Weigand, Peter
T1  - Host-pathogen interactions in bacterial meningitis
JF  - Acta Neuropathologica
N2  - Bacterial meningitis is a devastating disease occurring worldwide with up to half of the survivors left with permanent neurological sequelae. Due to intrinsic properties of the meningeal pathogens and the host responses they induce, infection can cause relatively specific lesions and clinical syndromes that result from interference with the function of the affected nervous system tissue. Pathogenesis is based on complex host-pathogen interactions, some of which are specific for certain bacteria, whereas others are shared among different pathogens. In this review, we summarize the recent progress made in understanding the molecular and cellular events involved in these interactions. We focus on selected major pathogens, Streptococcus pneumonia, S. agalactiae (Group B Streptococcus), Neisseria meningitidis, and Escherichia coli K1, and also include a neglected zoonotic pathogen, Streptococcus suis. These neuroinvasive pathogens represent common themes of host-pathogen interactions, such as colonization and invasion of mucosal barriers, survival in the blood stream, entry into the central nervous system by translocation of the blood-brain and blood-cerebrospinal fluid barrier, and induction of meningeal inflammation, affecting pia mater, the arachnoid and subarachnoid spaces.
KW  - microvascular endothelial cells
KW  - outer membrane protein
KW  - Neuroinfectiology
KW  - Bacterial meningitis
KW  - Pneumococci
KW  - Meningococci
KW  - Group B Streptococcus
KW  - Streptococcus suis
KW  - Escherichia coli K1
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191034
VL  - 131
IS  - 2
ER  - 
TY  - JOUR
A1  - Hubert, Kerstin
A1  - Pawlik, Marie-Christin
A1  - Claus, Heike
A1  - Jarva, Hanna
A1  - Meri, Seppo
A1  - Vogel, Ulrich
T1  - Opc Expression, LPS Immunotype Switch and Pilin Conversion Contribute to Serum Resistance of Unencapsulated Meningococci
JF  - PLoS One
N2  - 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.
KW  - factor H
KW  - C-reactive protein
KW  - B neisseria meningitidis
KW  - outer membrane protein
KW  - phase variation
KW  - serogroup B
KW  - bactericidal activity
KW  - epithelial cells
KW  - gene conversion
KW  - strain MC58
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135421
VL  - 7
IS  - 9
ER  -