TY - JOUR
T1 - BspR/BtrA, an Anti-σ factor, regulates the ability of Bordetella bronchiseptica to cause cough in rats
AU - Nakamura, Keiji
AU - Shinoda, Noriko
AU - Hiramatsu, Yukihiro
AU - Ohnishi, Shinya
AU - Kamitani, Shigeki
AU - Ogura, Yoshitoshi
AU - Hayashi, Tetsuya
AU - Horiguchi, Yasuhiko
N1 - Funding Information:
We thank P. A. Cotter for B. bronchiseptica RB50, A. Abe for the ▴bscN and ▴bspR strains, pABB-CRS2, and the anti-BspR antibody, and K. Minamisawa for the E. coli strains carrying pRK2013. We also thank H. Abe and M. Kobayashi for technical support for the gene manipulation and animal experiments. This study was supported by JSPS KAKENHI grants JP16K19124, JP18K15146, JP23390104, and JP26293096, as well as the Waksman Foundation of Japan, Novartis research grant 11-107, and The Naito Foundation Natural Science Scholarship. The authors declare no competing financial interests. K.N. and N.S. performed the majority of the animal experiments and generation of bacterial mutant strains. Y.H., S.O., and S.K. contributed to establishing the protocol for the animal experiments. Y.O. and T.H. performed the experiments related to the whole-genome sequences. Y.H. designed the experiments and wrote the manuscript.
Publisher Copyright:
© 2019 Nakamura et al.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
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U2 - 10.1128/MSPHERE.00093-19
DO - 10.1128/MSPHERE.00093-19
M3 - Article
C2 - 31019000
AN - SCOPUS:85065314981
VL - 4
JO - mSphere
JF - mSphere
SN - 2379-5042
IS - 2
M1 - e00093-19
ER -