Campylobacter hyointestinalis Isolated from Pigs Produces Multiple Variants of Biologically Active Cytolethal Distending Toxin.
Campylobacter hyointestinalis isolated from swine with proliferative enteritis often is considered to be pathogenic. While the precise virulence mechanisms of this species remain unclear, we have recently identified a cytolethal distending toxin (cdt) gene cluster in C. hyointestinalis isolated from a patient with diarrhea (W. Samosornsuk et al., J Med Microbiol, 27 July 2015, http://dx.doi.org/10.1099/jmm.0.000145). However, the sequences of the cdt genes in C. hyointestinalis were found to be significantly different and the gene products are immunologically distinct from those of other Campylobacter species. In this study, we demonstrate the presence of a second variant of the cdt gene cluster in C. hyointestinalis, designated cdt-II, while the former is named cdt-I. Sequencing of the cdt-II gene cluster and deduced amino acid sequences revealed that homologies between the subunits CdtA, CdtB, and CdtC of ChCDT-I and ChCDT-II are 25.0, 56.0, and 24.8%, respectively. Furthermore, the CdtB subunit of ChCDT-II was found to be immunologically unrelated to that of ChCDT-I by Ouchterlony double gel diffusion test. Recombinant ChCDT-II also induced cell distention and death of HeLa cells by blocking the cell cycle at G2/M phase. Interestingly, the cdt-II genes were detected in all 23 animal isolates and in 1 human isolate of C. hyointestinalis, and 21 of these strains carried both cdt-I and cdt-II gene clusters. Altogether, our results indicate that ChCDT-II is an important virulence factor of C. hyointestinalis in animals.
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Kazumasa
K
Kamei
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Noritoshi
N
Hatanaka
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Masahiro
M
Asakura
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Srinuan
S
Somroop
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan Faculty of Allied Health Sciences, Thammassat University, Bangkok, Thailand.
Worada
W
Samosornsuk
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Atsushi
A
Hinenoya
Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
Naoaki
N
Misawa
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Shinsaku
S
Nakagawa
Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan shinji@vet.osakafu-u.ac.jp.
Shinji
S
Yamasaki
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D002169:Campylobacter Infections / Q000382:microbiology* / Q000503:physiopathology / Q000662:veterinary*; D044862:Campylobacter hyointestinalis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology*
D001427:Bacterial Toxins; C067044:cytolethal distending toxin