Identification of a conserved Moraxella catarrhalis haemoglobin-utilization protein, MhuA

Furano, Kristin; Luke, Nicole R.; Howlett, Amy J.; Campagnari, Anthony A.

doi:10.1099/mic.0.27820-0

Cited by 14 publications

(10 citation statements)

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“…This led to the identification of a highly conserved 107-kDa OMP, MhuA, which was detected in a collection of geographically diverse clinical isolates. The MhuA protein of M. catarrhalis 7169 directly binds to human hemoglobin, and an mhuA isogenic mutant showed reduced growth on hemoglobin as a sole iron source, though not when grown on heme or Fe(NO 3 ) 3 (47). Further, surface-exposed TFP also appear to be important for growth under iron-limiting conditions.…”

Section: Iron Acquisitionmentioning

confidence: 99%

“…Lactoferrin is the primary carrier of iron on mucosal surfaces, whereas transferrin is the most important iron carrier in serum, and the sequestration of iron is an important line of defense against pathogenic bacteria (119). The acquisition of iron by M. catarrhalis is mediated by several surface- exposed iron-binding proteins: two lactoferrin-binding proteins (LbpA and LbpB) (35), two transferrin-binding proteins (TbpA and TbpB) (154), CopB (4), the heme utilization protein (HumA), (46), and the M. catarrhalis hemoglobin utilization protein (MhuA) (47). M. catarrhalis strain ATCC 25240 was found to be able to utilize both human transferrin and lactoferrin as iron sources.…”

Section: Iron Acquisitionmentioning

confidence: 99%

“…However, it is possible that hemoglobin could become available to M. catarrhalis during episodes of acute OM. Furano et al demonstrated that M. catarrhalis was able to use hemoglobin as a source of iron during in vitro growth (47). This led to the identification of a highly conserved 107-kDa OMP, MhuA, which was detected in a collection of geographically diverse clinical isolates.…”

Section: Iron Acquisitionmentioning

confidence: 99%

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Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY In recent years, Moraxella catarrhalis has established its position as an important human mucosal pathogen, no longer being regarded as just a commensal bacterium. Further, current research in the field has led to a better understanding of the molecular mechanisms involved in M. catarrhalis pathogenesis, including mechanisms associated with cellular adherence, target cell invasion, modulation of the host's immune response, and metabolism. Additionally, in order to be successful in the host, M. catarrhalis has to be able to interact and compete with the commensal flora and overcome stressful environmental conditions, such as nutrient limitation. In this review, we provide a timely overview of the current understanding of the molecular mechanisms associated with M. catarrhalis virulence and pathogenesis.

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Section: Iron Acquisitionmentioning

confidence: 99%

Section: Iron Acquisitionmentioning

confidence: 99%

Section: Iron Acquisitionmentioning

confidence: 99%

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Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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“…Iron is a key nutrient that is functionally involved as a cofactor in various metabolic processes and is essential for both M. catarrhalis and its human host (56). The RH4 genome contains genes encoding components of many iron acquisition and transport systems (see Table S8 in the supplemental material), including all of the following M. catarrhalis proteins previously described as proteins involved in this process: lactoferrin binding proteins A and B (17), transferrin binding proteins A and B (74), heme utilization protein (25), M. catarrhalis hemoglobin utilization protein (26), CopB (1), and the main regulator of iron-responsive genes, Fur (24). In addition, iron may be acquired through degradation of heme, which is catalyzed by a heme oxygenase.…”

Section: Central Metabolic Pathwaysmentioning

confidence: 99%

Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen

et al. 2010

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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 ...

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“…M. catarrhalis expresses some OMPs, including the transferrin binding protein TbpB (28) and the hemin and hemoglobin utilization proteins HumA and MhuA (11,12), to obtain iron from the human host. In addition, other OMPs, such as the ubiquitous surface protein UspA2, can be involved in serum resistance (1) or in natural competence, as described for the type IV pilus (26).…”

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confidence: 99%

Identification of a Novel Two-Partner Secretion Locus in Moraxella catarrhalis

Plamondon

Luke²,

Campagnari

2007

Infect Immun

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Although Moraxella catarrhalis continues to be a significant cause of disease in both children and adults, the steps involved in pathogenesis remain poorly understood. We have identified three open reading frames in the M. catarrhalis genome that encode homologues of the two-partner secretion system (TPS) Moraxella catarrhalis is an important gram-negative human mucosal pathogen. It is one of the three major causes of acute otitis media, along with Streptococcus pneumoniae and nontypeable Haemophilus influenzae (10, 43). In adults with chronic bronchitis and chronic obstructive pulmonary disease (COPD), M. catarrhalis causes lower respiratory tract infections that often lead to acute exacerbations (33, 34). In addition, M. catarrhalis can cause sinusitis in infants and young children (23,43). Because 90% of M. catarrhalis clinical isolates are beta-lactamase positive (23,43) and no protective vaccine is available (29, 30), M. catarrhalis continues to be a major source of human disease..Most of the research involving M. catarrhalis pathogenesis has focused largely on the identification and characterization of outer membrane proteins (OMPs) on the bacterial surface, although most of these have an undefined role in virulence (23,32,43). M. catarrhalis expresses some OMPs, including the transferrin binding protein TbpB (28) and the hemin and hemoglobin utilization proteins HumA and MhuA (11,12), to obtain iron from the human host. In addition, other OMPs, such as the ubiquitous surface protein UspA2, can be involved in serum resistance (1) or in natural competence, as described for the type IV pilus (26). To date, only a few OMPs, including UspA1 and UspA2H (1, 24), the M. catarrhalis adherence protein McaP (41), and the hemagglutinating protein Hag/M. catarrhalis immunoglobulin D-binding protein (3,14,19), have been reported to directly mediate binding to cell lines in vitro. Therefore, it is clear that like many other gram-negative pathogens, M. catarrhalis has developed multiple virulence mechanisms to successfully colonize the human mucosal surface.In this report, we have identified a locus in M. catarrhalis 7169 containing three open reading frames (ORFs) that encode homologues of the previously described two-partner secretion systems (TPS) in various other pathogens, including Bordetella pertussis (21,22). The B. pertussis TPS pathway is composed of the filamentous hemagglutinin FhaB (generically named TpsA) and the transporter FhaC (TpsB) (25). FhaB is the major adhesin involved in bacterial attachment and colonization of the human upper respiratory tract, and this protein is also a component of the acellular diphtheria-pertussis vaccine (25, 36). The M. catarrhalis hemagglutinin-like locus described in this study contains three ORFs, termed mchA1, mchA2, and mchB. The TPS motif identified in MchA1 and MchA2 was found to be homologous to FhaB of B. pertussis. MchB has homology to FhaC of B. pertussis (22). This is the first report of a TPS in M. catarrhalis, and our data demonstrate that this system is likely...

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Identification of a conserved Moraxella catarrhalis haemoglobin-utilization protein, MhuA

Cited by 14 publications

References 50 publications

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen

Identification of a Novel Two-Partner Secretion Locus in Moraxella catarrhalis

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