Abstract
BackgroundMoraxella catarrhalis is a human-specific gram-negative bacterium readily isolated from the respiratory tract of healthy individuals. The organism also causes significant health problems, including 15-20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease. The lack of an efficacious vaccine, the rapid emergence of antibiotic resistance in clinical isolates, and high carriage rates reported in children are cause for concern. Virtually all Moraxella catarrhalis isolates are resistant to β-lactam antibiotics, which are generally the first antibiotics prescribed to treat otitis media in children. The enzymes responsible for this resistance, BRO-1 and BRO-2, are lipoproteins and the mechanism by which they are secreted to the periplasm of M. catarrhalis cells has not been described.ResultsComparative genomic analyses identified M. catarrhalis gene products resembling the TatA, TatB, and TatC proteins of the well-characterized Twin Arginine Translocation (TAT) secretory apparatus. Mutations in the M. catarrhalis tatA, tatB and tatC genes revealed that the proteins are necessary for optimal growth and resistance to β-lactams. Site-directed mutagenesis was used to replace highly-conserved twin arginine residues in the predicted signal sequence of M. catarrhalis strain O35E BRO-2, which abolished resistance to the β-lactam antibiotic carbanecillin.ConclusionsMoraxella catarrhalis possesses a TAT secretory apparatus, which plays a key role in growth of the organism and is necessary for secretion of BRO-2 into the periplasm where the enzyme can protect the peptidoglycan cell wall from the antimicrobial activity of β-lactam antibiotics.
Highlights
Moraxella catarrhalis is a human-specific gram-negative bacterium readily isolated from the respiratory tract of healthy individuals
Moraxella catarrhalis is a Gram-negative bacterium primarily associated with otitis media in children and respiratory infections in adults with compromised lung function, patients with Chronic Obstructive Pulmonary Disease (COPD)
Upstream of the M. catarrhalis tatB-like gene, we identified an Open reading frame (ORF) specifying a 9-kDa protein of 77 aa that is most similar to TatA of Xanthomonas oryzae [77]
Summary
Moraxella catarrhalis is a human-specific gram-negative bacterium readily isolated from the respiratory tract of healthy individuals. Moraxella catarrhalis is a Gram-negative bacterium primarily associated with otitis media in children and respiratory infections in adults with compromised lung function, patients with Chronic Obstructive Pulmonary Disease (COPD). A number of molecules in the outer membrane have been shown to contribute to adherence, allowing M. catarrhalis to bind and colonize the host mucosa. These include LOS, UspA1, UspA2H, McaP, OMPCD, Hag/MID, MhaB1, MhaB2, MchA1, MchA2, and the type IV pilus [28,29,30,31,32,33,34,35,36,37]. The best studied of these being UspA2 and UspA2H, which bind the C4-binding protein, C3 and vitronectin [38,39,40,41], as well as CopB, OMPCD, OmpE, and LOS [31,37,42,43]
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