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, which originally was isolated from blood of an infected patient. The RH4 genome consists of 1,863,286 nucleotides that form 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 almost the entire repertoire of known M. catarrhalis virulence factors and mapped the members of the biosynthetic pathways for lipooligosaccharide, peptidoglycan, and type IV pili. Reconstruction of the central metabolic pathways suggested that RH4 relies on fatty acid and acetate metabolism, as the genes encoding the enzymes required for the glyoxylate pathway, the tricarboxylic acid cycle, the gluconeogenic pathway, the nonoxidative branch of the pentose phosphate pathway, the beta-oxidation pathway of fatty acids, and acetate metabolism were present. Moreover, pathways important for survival under challenging in vivo conditions, such as the iron-acquisition pathways, nitrogen metabolism, and oxidative stress responses, were identified. Finally, we showed by microarray expression profiling that ϳ88% 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.Moraxella catarrhalis is an emerging human-restricted unencapsulated Gram-negative mucosal pathogen. Long considered to be a commensal of the upper respiratory tract, this bacterium has now firmly been established to be an etiological cause of otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). It is the third most common cause of childhood OM after Haemophilus influenzae and Streptococcus pneumoniae (37, 64), and it is responsible for up to 20% of the cases (64, 65). Further, M. catarrhalis is the second most common cause of exacerbations of COPD after H. influenzae; it is responsible for 10 to 15% of the exacerbations and annually causes 2 to 4 million episodes in the United States (47, 60). Antibiotics are widely used for treatment of OM, but the high prevalence of this disease and the increasing incidence of antibiotic-resistant strains mean that multivalent vaccines, preferably vaccines with protective antigens for all three causative bacterial agents, must be developed (46).M. catarrhalis is able to colonize the mucosal surfaces of the middle ear in OM patients and the lower respiratory tract in COPD patients (31,60). Successful colonization of the human host is a complex process which requires the expression ...

The internal hydrophobic sequence within the flaviviral capsid protein (protein C) plays an important role in the assembly of infectious virions. Here, this sequence was analyzed in a West Nile virus lineage I isolate (crow V76/1). An infectious cDNA clone was constructed and used to introduce deletions into the internal hydrophobic domain which comprises helix ␣2 and part of the loop intervening helices ␣2 and ␣3. In total, nine capsid deletion mutants (4 to 14 amino acids long) were constructed and tested for virus viability. Some of the short deletions did not significantly affect growth in cell culture, whereas larger deletions removing almost the entire hydrophobic region significantly impaired viral growth. Efficient growth of the majority of mutants could, however, be restored by the acquisition of second-site mutations. In most cases, these resuscitating mutations were point mutations within protein C changing individual amino acids into more hydrophobic residues, reminiscent of what had been observed previously for another flavivirus, tick-borne encephalitis virus. However, we also identified viable spontaneous pseudorevertants with more than one-third of the capsid protein removed, i.e., 36 or 37 of a total of 105 residues, including all of helix ␣3 and a hydrophilic segment connecting ␣3 and ␣4. These large deletions are predicted to induce formation of large, predominantly hydrophobic fusion helices which may substitute for the loss of the internal hydrophobic domain, underlining the unrivaled structural and functional flexibility of protein C.The genus Flavivirus within the family Flaviviridae comprises important human pathogens such as Japanese encephalitis virus (JEV), the dengue viruses (DENV), yellow fever virus (YFV), tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) (28). The ϳ50-nm flavivirus virion is composed of two surface proteins, envelope (E) and membrane (M, derived from its precursor protein prM by furin-mediated cleavage), and the nucleocapsid consisting of the capsid protein (protein C) and the 11-kb positive-stranded RNA genome. In addition to the three structural proteins C, prM, and E, the genome encodes seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), which are necessary for replication of the RNA genome (28). Structural and nonstructural proteins are derived from a single polyprotein, which is co-and posttranslationally processed into mature proteins by viral and cellular proteases (6, 28).The assembly of the virions is thought to occur at the membrane of the rough endoplasmic reticulum (ER) (28, 32). Protein C, which is the protein located at the very N terminus of the polyprotein, facilitates translocation of the subsequent protein prM into the lumen of the ER via an internal signal sequence located at its C terminus. Proteins prM and E remain attached to the host-derived membrane by spanning the lipid bilayer twice via their C-terminal anchor regions (38,47,48). Protein C is originally also anchored to the ER membrane via the C-terminal ...

The genome sequence described is that of strain BBH18, isolated from sputum, and not of strain RH4, which was isolated from blood. Consequently, the title should read "Genome Analysis of Moraxella catarrhalis Strain BBH18, a Human Respiratory Tract Pathogen," and the strain name RH4 should be replaced by BBH18 throughout the manuscript. Furthermore, in the abstract (page 3574, line 4), introduction (page 3574, column 2, line 27), and Materials and Methods (page 3575, column 1, lines 13 and 14), the phrase "isolated from blood of an infected patient (14)" should be changed to "isolated from sputum of a patient with COPD during an exacerbation (45)." The correct reference for strain BBH18 is reference 45 (A.