BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals t...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-04-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00093-19 |
| _version_ | 1818836623100477440 |
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| author | Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi |
| author_facet | Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi |
| author_sort | Keiji Nakamura |
| collection | DOAJ |
| description | ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing after Bordetella infection. Here, we present a coughing model of rats infected with B. bronchiseptica. Rats, which are one of natural hosts of B. bronchiseptica, were readily infected with the organisms and showed frequent coughing. B. pertussis also caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than the B. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection with bspR (btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from a bspR (btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced by B. bronchiseptica in the Bvg+ phase. We consider that our rat model provides insight into the pathogenesis of cough induced by the Bordetella infection. IMPORTANCE Whooping cough is a contagious respiratory disease caused by Bordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing Bordetella-induced coughing is the lack of conventional animal models that replicate coughing. As Bordetella pertussis is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with B. bronchiseptica, which shares many virulence factors with B. pertussis. Using this rat model, we demonstrated that some of the major virulence factors of Bordetella are not involved in cough production, but an anti-σ factor, BspR/BtrA, of B. bronchiseptica regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which Bordetella induces cough. |
| first_indexed | 2024-12-19T03:09:33Z |
| format | Article |
| id | doaj.art-4859917f5bfa4da89f817ab28213c364 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T03:09:33Z |
| publishDate | 2019-04-01 |
| publisher | American Society for Microbiology |
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| series | mSphere |
| spelling | doaj.art-4859917f5bfa4da89f817ab28213c3642022-12-21T20:38:03ZengAmerican Society for MicrobiologymSphere2379-50422019-04-014210.1128/mSphere.00093-19BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in RatsKeiji Nakamura0Noriko Shinoda1Yukihiro Hiramatsu2Shinya Ohnishi3Shigeki Kamitani4Yoshitoshi Ogura5Tetsuya Hayashi6Yasuhiko Horiguchi7Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanDepartment of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, JapanABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing after Bordetella infection. Here, we present a coughing model of rats infected with B. bronchiseptica. Rats, which are one of natural hosts of B. bronchiseptica, were readily infected with the organisms and showed frequent coughing. B. pertussis also caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than the B. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection with bspR (btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from a bspR (btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced by B. bronchiseptica in the Bvg+ phase. We consider that our rat model provides insight into the pathogenesis of cough induced by the Bordetella infection. IMPORTANCE Whooping cough is a contagious respiratory disease caused by Bordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing Bordetella-induced coughing is the lack of conventional animal models that replicate coughing. As Bordetella pertussis is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with B. bronchiseptica, which shares many virulence factors with B. pertussis. Using this rat model, we demonstrated that some of the major virulence factors of Bordetella are not involved in cough production, but an anti-σ factor, BspR/BtrA, of B. bronchiseptica regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which Bordetella induces cough.https://journals.asm.org/doi/10.1128/mSphere.00093-19BordetellaBspR/BtrAcough |
| spellingShingle | Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats mSphere Bordetella BspR/BtrA cough |
| title | BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats |
| title_full | BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats |
| title_fullStr | BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats |
| title_full_unstemmed | BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats |
| title_short | BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats |
| title_sort | bspr btra an anti σ factor regulates the ability of italic toggle yes bordetella bronchiseptica italic to cause cough in rats |
| topic | Bordetella BspR/BtrA cough |
| url | https://journals.asm.org/doi/10.1128/mSphere.00093-19 |
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