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Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2
BACKGROUND: Moraxella 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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695778/ https://www.ncbi.nlm.nih.gov/pubmed/23782650 http://dx.doi.org/10.1186/1471-2180-13-140 |
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author | Balder, Rachel Shaffer, Teresa L Lafontaine, Eric R |
author_facet | Balder, Rachel Shaffer, Teresa L Lafontaine, Eric R |
author_sort | Balder, Rachel |
collection | PubMed |
description | BACKGROUND: Moraxella 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. RESULTS: Comparative 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. CONCLUSIONS: Moraxella 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. |
format | Online Article Text |
id | pubmed-3695778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36957782013-06-29 Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 Balder, Rachel Shaffer, Teresa L Lafontaine, Eric R BMC Microbiol Research Article BACKGROUND: Moraxella 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. RESULTS: Comparative 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. CONCLUSIONS: Moraxella 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. BioMed Central 2013-06-19 /pmc/articles/PMC3695778/ /pubmed/23782650 http://dx.doi.org/10.1186/1471-2180-13-140 Text en Copyright © 2013 Balder et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Balder, Rachel Shaffer, Teresa L Lafontaine, Eric R Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title | Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title_full | Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title_fullStr | Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title_full_unstemmed | Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title_short | Moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase BRO-2 |
title_sort | moraxella catarrhalis uses a twin-arginine translocation system to secrete the β-lactamase bro-2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695778/ https://www.ncbi.nlm.nih.gov/pubmed/23782650 http://dx.doi.org/10.1186/1471-2180-13-140 |
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