TY  - JOUR
A1  - Roier, Sandro
A1  - Leitner, Deborah R.
A1  - Iwashkiw, Jeremy
A1  - Schild-Prüfert, Kristina
A1  - Feldman, Mario F.
A1  - Krohne, Georg
A1  - Reidl, Joachim
A1  - Schild, Stefan
T1  - Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice
JF  - PLoS One
N2  - Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.
KW  - conjugate
KW  - obstructive pulmonary disease
KW  - vaccine
KW  - vibrio cholerae
KW  - detoxified lipooligosaccharide
KW  - nasopharyngeal colonization
KW  - functional characterization
KW  - growing escherichia coli
KW  - DNA-binding vesicles
KW  - otitis media
KW  - hemophilus influenzae
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135201
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Lichtenegger, Sabine
A1  - Bina, Isabelle
A1  - Roier, Sandro
A1  - Bauernfeind, Stilla
A1  - Keidel, Kristina
A1  - Schild, Stefan
A1  - Anthony, Mark
A1  - Reidl, Joachim
T1  - Characterization of lactate utilization and its implication on the physiology of Haemophilus influenzae
JF  - International Journal of Medical Microbiology
N2  - Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake is 20.1μM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi 2019-R with the corresponding lctP knockout strain for survival in human serum revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold attenuation of the mutant strain in a murine model of nasopharyngeal colonization. Characterization of lctP transcriptional control shows that the lactate utilization system in H. influenzae is not an inductor inducible system. Rather negative feedback regulation was observed in the presence of l-lactate and this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was found that lactate may have signaling function leading to increased cell growth in late log phase under conditions where no l-lactate is metabolized. This effect seems to be ArcA independent and was not observed in strain Rd KW20. We conclude that l-lactate is an important carbon-source and may act as host specific signal substrate which fine tunes the globally acting ArcAB regulon and may additionally affect a yet unknown signaling system and thus may contribute to enhanced in vivo survival.
KW  - colonization
KW  - haemophilus influenzae
KW  - I-lactate
KW  - utilization
KW  - IctP
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121335
VL  - 304
IS  - 3-4
ER  -