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Identification of a conserved Moraxella catarrhalis haemoglobin-utilization protein, MhuA
Kristin Furano1,2, Nicole R Luke1,2, Amy J Howlett1,2
1Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Abstract:
Moraxella catarrhalis is a leading cause of acute otitis media in children and is a cause of respiratory disease in adults with underlying lung disease. This organism is a strict human pathogen that has an absolute requirement for iron in order to grow and cause disease. Previous studies identified transferrin and lactoferrin receptors used by M. catarrhalis to obtain iron from the human host, yet other iron-acquisition systems remain undefined. In this study, it is demonstrated that this strict mucosal pathogen can utilize haemoglobin (Hb) as a sole source of iron for growth. A novel 107 kDa outer-membrane protein involved in Hb utilization by this pathogen was also identified. An isogenic mutant defective in this Moraxella Hb-utilization protein (MhuA), 7169 : : mhuA, showed a significant lag during growth in the presence of Hb as the sole iron source. This protein appears to be expressed constitutively, regardless of growth conditions, and a mAb directed to MhuA demonstrated that this protein contains highly conserved, surface-exposed epitopes. Data demonstrating that expression of MhuA may be highly specific to isolates of M. catarrhalis are also presented, suggesting a potential role as a diagnostic marker. To our knowledge, this is the first report demonstrating that M. catarrhalis expresses an Hb-binding protein and that this bacterium can utilize Hb as a sole iron source for growth.
Insights
Moraxella catarrhalis, a pathogen causing ear and lung infections, can use hemoglobin (Hb) as its sole iron source. A novel Hb-utilization protein (MhuA) was identified, crucial for this iron acquisition.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Iron Metabolism
Background:
- Moraxella catarrhalis is a significant human pathogen responsible for acute otitis media in children and respiratory infections in adults.
- Iron is essential for M. catarrhalis growth and virulence, with known acquisition mechanisms involving transferrin and lactoferrin.
- Other iron acquisition systems in M. catarrhalis remain incompletely understood.
Purpose of the Study:
- To investigate the ability of Moraxella catarrhalis to utilize hemoglobin (Hb) as an iron source.
- To identify and characterize novel proteins involved in Hb utilization by M. catarrhalis.
- To assess the potential of identified proteins as diagnostic markers.
Main Methods:
- Growth assays using hemoglobin as the sole iron source.
- Construction and analysis of an isogenic mutant (7169::mhuA) lacking the Moraxella Hb-utilization protein (MhuA).
- Characterization of MhuA expression and surface epitopes using monoclonal antibodies (mAbs).
Main Results:
- Moraxella catarrhalis can grow using hemoglobin as its sole iron source.
- A novel 107 kDa outer-membrane protein, MhuA, was identified as essential for Hb utilization.
- The mhuA mutant exhibited a significant growth lag in the presence of Hb as the sole iron source.
- MhuA is constitutively expressed and possesses conserved, surface-exposed epitopes.
- MhuA expression appears specific to M. catarrhalis isolates, suggesting diagnostic potential.
Conclusions:
- Moraxella catarrhalis possesses a novel system for iron acquisition via hemoglobin utilization, mediated by the MhuA outer-membrane protein.
- MhuA is a surface-exposed protein critical for bacterial growth on hemoglobin.
- MhuA represents a potential species-specific diagnostic marker for Moraxella catarrhalis infections.
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