The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids
ABSTRACTWhooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vacci...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1601502 |
| _version_ | 1797385743702687744 |
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| author | Iain MacArthur Thomas Belcher Jerry D. King Vasantha Ramasamy Munirah Alhammadi Andrew Preston |
| author_facet | Iain MacArthur Thomas Belcher Jerry D. King Vasantha Ramasamy Munirah Alhammadi Andrew Preston |
| author_sort | Iain MacArthur |
| collection | DOAJ |
| description | ABSTRACTWhooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vaccines. It is inhibited by fatty acids and other hydrophobic molecules. The AcrAB efflux system is present in many different bacteria and in combination with an outer membrane factor exports acriflavine and other small hydrophobic molecules from the cell. Here, we identify that the speciation of B. pertussis has selected for an Acr system that is naturally mutated and displays reduced activity compared to B. bronchiseptica, in which the system appears intact. Replacement of the B. pertussis locus with that of B. bronchiseptica conferred higher levels of resistance to growth inhibition by acriflavine and fatty acids. In addition, we identified that the transcription of the locus is repressed by a LysR-type transcriptional regulator. Palmitate de-represses the expression of the acr locus, dependent on the LysR regulator, strongly suggesting that it is a transcriptional repressor that is regulated by palmitate. It is intriguing that the speciation of B. pertussis has selected for a reduction in activity of the Acr efflux system that typically is regarded as protective to bacteria. |
| first_indexed | 2024-03-08T21:58:40Z |
| format | Article |
| id | doaj.art-096f26d16e5e4a198c4e2ed01fd0d093 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-08T21:58:40Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-096f26d16e5e4a198c4e2ed01fd0d0932023-12-19T16:09:58ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-018160361210.1080/22221751.2019.1601502The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acidsIain MacArthur0Thomas Belcher1Jerry D. King2Vasantha Ramasamy3Munirah Alhammadi4Andrew Preston5The Milner Centre for Evolution, University of Bath, Bath, UKDepartment of Biology and Biochemistry, University of Bath, Bath, UKDepartment of Biology and Biochemistry, University of Bath, Bath, UKDepartment of Biology and Biochemistry, University of Bath, Bath, UKDepartment of Biology and Biochemistry, University of Bath, Bath, UKThe Milner Centre for Evolution, University of Bath, Bath, UKABSTRACTWhooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vaccines. It is inhibited by fatty acids and other hydrophobic molecules. The AcrAB efflux system is present in many different bacteria and in combination with an outer membrane factor exports acriflavine and other small hydrophobic molecules from the cell. Here, we identify that the speciation of B. pertussis has selected for an Acr system that is naturally mutated and displays reduced activity compared to B. bronchiseptica, in which the system appears intact. Replacement of the B. pertussis locus with that of B. bronchiseptica conferred higher levels of resistance to growth inhibition by acriflavine and fatty acids. In addition, we identified that the transcription of the locus is repressed by a LysR-type transcriptional regulator. Palmitate de-represses the expression of the acr locus, dependent on the LysR regulator, strongly suggesting that it is a transcriptional repressor that is regulated by palmitate. It is intriguing that the speciation of B. pertussis has selected for a reduction in activity of the Acr efflux system that typically is regarded as protective to bacteria.https://www.tandfonline.com/doi/10.1080/22221751.2019.1601502Bordetella pertussisacrevolutiongrowth inhibitionpalmitaterepressor |
| spellingShingle | Iain MacArthur Thomas Belcher Jerry D. King Vasantha Ramasamy Munirah Alhammadi Andrew Preston The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids Emerging Microbes and Infections Bordetella pertussis acr evolution growth inhibition palmitate repressor |
| title | The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| title_full | The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| title_fullStr | The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| title_full_unstemmed | The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| title_short | The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| title_sort | evolution of bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids |
| topic | Bordetella pertussis acr evolution growth inhibition palmitate repressor |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1601502 |
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