| 1. |
- de Vries, Stefan P W, et al.
(författare)
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Genome analysis of Moraxella catarrhalis strain RH4, a Human Respiratory Tract Pathogen.
- 2010
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Ingår i: Journal of Bacteriology. - 0021-9193. ; 192:14, s. 3574-3583
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Tidskriftsartikel (refereegranskat)abstract
- Moraxella catarrhalis is an emerging human-restricted respiratory tract pathogen that is a common cause of childhood otitis media and exacerbations of chronic obstructive pulmonary disease in adults. Here, we report the first completely assembled and annotated genome sequence of an isolate of M. catarrhalis: strain RH4, originally isolated from blood of an infected patient. The RH4 genome consists of 1,863,286 nucleotides harboring 1,886 protein-encoding genes. Comparison of the RH4 genome to the ATCC 43617 contigs demonstrated that the gene content of both strains is highly conserved. In silico phylogenetic analyses based on both 16S rRNA and multilocus sequence typing revealed that RH4 belongs to the seroresistant lineage. We were able to identify close to the entire repertoire of known M. catarrhalis virulence factors, and mapped the members of the biosynthetic pathways for lipooligosaccharide, peptidoglycan, and type IV pili. A reconstruction of the central metabolic pathways suggests that RH4 relies on fatty acid and acetate metabolism, as the genes encoding the enzymes required for the glyoxylate pathway, tricarboxylic acid cycle, gluconeogenic pathway, non-oxidative branch of the pentose phosphate pathway, beta-oxidation pathway of fatty acids, and acetate metabolism were present. Moreover, pathways important for survival under in vivo challenging conditions such as iron-acquisition pathways, nitrogen metabolism, and oxidative stress responses were identified. Finally, we showed by microarray expression profiling that approximately 88% of the predicted coding sequences are transcribed under in vitro conditions. Overall, these results provide a foundation for future research into the mechanisms of M. catarrhalis pathogenesis and vaccine development.
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| 2. |
- Langereis, Jeroen D, et al.
(författare)
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Modified Lipooligosaccharide Structure Protects Nontypeable Haemophilus influenzae from IgM-Mediated Complement Killing in Experimental Otitis Media
- 2012
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Ingår i: mBio. - : American Society for Microbiology: mBio / American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative, human-restricted pathogen. Although this bacterium typically colonizes the nasopharynx in the absence of clinical symptoms, it is also one of the major pathogens causing otitis media (OM) in children. Complement represents an important aspect of the host defense against NTHi. In general, NTHi is efficiently killed by complement-mediated killing; however, various resistance mechanisms have also evolved. We measured the complement resistance of NTHi isolates isolated from the nasopharynx and the middle ear fluids of OM patients. Furthermore, we determined the molecular mechanism of NTHi complement resistance. Complement resistance was strongly increased in isolates from the middle ear, which correlated with decreased binding of IgM. We identified a crucial role for the R2866_0112 gene in complement resistance. Deletion of this gene altered the lipooligosaccharide (LOS) composition of the bacterium, which increased IgM binding and complement-mediated lysis. In a novel mouse model of coinfection with influenza virus, we demonstrate decreased virulence for the R2866_0112 deletion mutant. These findings identify a mechanism by which NTHi modifies its LOS structure to prevent recognition by IgM and activation of complement. Importantly, this mechanism plays a crucial role in the ability of NTHi to cause OM. less thanbrgreater than less thanbrgreater thanIMPORTANCE Nontypeable Haemophilus influenzae (NTHi) colonizes the nasopharynx of especially young children without any obvious symptoms. However, NTHi is also a major pathogen in otitis media (OM), one of the most common childhood infections. Although this pathogen is often associated with OM, the mechanism by which this bacterium is able to cause OM is largely unknown. Our study addresses a key biological question that is highly relevant for child health: what is the molecular mechanism that enables NTHi to cause OM? We show that isolates collected from the middle ear fluid exhibit increased complement resistance and that the lipooligosaccharide (LOS) structure determines IgM binding and complement activation. Modification of the LOS structure decreased NTHi virulence in a novel NTHi-influenza A virus coinfection OM mouse model. Our findings may also have important implications for other Gram-negative pathogens harboring LOS, such as Neisseria meningitidis, Moraxella catarrhalis, and Bordetella pertussis.
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| 3. |
- Schaar, Viveka, et al.
(författare)
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Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells.
- 2011
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814. ; Dec, s. 432-449
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Tidskriftsartikel (refereegranskat)abstract
- Moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (COPD) and in children with acute otitis media. The specific secretion machinery known as outer membrane vesicles (OMVs) is a mechanism by which Gram-negative pathogens interact with host cells during infection. We identified 57 proteins in M. catarrhalis OMVs using a proteomics approach combining two-dimensional SDS-PAGE and MALDI-TOF mass spectrometry analysis. The OMVs contained known surface proteins such as ubiquitous surface proteins (Usp) A1/A2, and Moraxella IgD-binding protein (MID). Most of the proteins are adhesins/virulence factors triggering the immune response, but also aid bacteria to evade the host defence. FITC-stained OMVs bound to lipid raft domains in alveolar epithelial cells and were internalized after interaction with Toll-like receptor 2 (TLR2), suggesting a delivery to the host tissue of a large and complex group of OMV-attributed proteins. Interestingly, OMVs modulated the pro-inflammatory response in epithelial cells, and UspA1-bearing OMVs were found to specifically downregulate the reaction. When mice were exposed to OMVs, a pulmonary inflammation was clearly seen. Our findings indicate that Moraxella OMVs are highly biologically active, transport main bacterial virulence factors and may modulate the epithelial pro-inflammatory response.
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| 4. |
- Zomer, Aldert, et al.
(författare)
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Genome Sequence of Moraxella catarrhalis RH4, an Isolate of Seroresistant Lineage
- 2012
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Ingår i: Journal of Bacteriology. - 0021-9193. ; 194:24, s. 6969-6969
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the annotated genome sequence of Moraxella catarrhalis strain RH4, a seroresistant-lineage strain isolated from the blood of an infected patient. This genome sequence will allow us to gain further insight into the genetic diversity of clinical M. catarrhalis isolates and will facilitate study of M. catarrhalis pathogenesis.
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