TY - JOUR
T1 - Export of a Vibrio parahaemolyticus toxin by the Sec and type III secretion machineries in tandem
AU - Matsuda, Shigeaki
AU - Okada, Ryu
AU - Tandhavanant, Sarunporn
AU - Hiyoshi, Hirotaka
AU - Gotoh, Kazuyoshi
AU - Iida, Tetsuya
AU - Kodama, Toshio
N1 - Funding Information:
We thank Y. Akiyama, H. Mori, Y. Hizukuri and E. Ishii (Kyoto University, Kyoto, Japan) for providing E.coli strains AD202, secY39, IT41 and IT42, and for critical discussions and reading of the manuscript. We also thank S. Miyoshi for the kind gift of the anti-VPP1 antibody and Y. Yamaichi for critical reading of the manuscript. This study was in part supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, grant 17K08828 (to S.M.) and grant 17K08829 (to T.K.). This work was also supported by Grants-in-Aid from the Institute for Fermentation, Osaka, from the Naito Foundation, and from the Takeda Science Foundation, Japan (to T.K.).
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Many Gram-negative pathogens utilize dedicated secretion systems to export virulence factors such as exotoxins and effectors 1–4 . Several exotoxins are synthesized as precursors containing amino-terminal Sec signal peptides and are exported through the inner-membrane-bound Sec machinery to the periplasm, followed by secretion across the outer membrane to the exterior using a type II secretion system (T2SS) 3,5 . Here, we report that thermostable direct haemolysin (TDH), an exotoxin of the food-borne pathogen Vibrio parahaemolyticus, can be exported through the type III secretion system (T3SS), which engages in one-step secretion of effectors 4 , despite possessing a Sec signal peptide and being mainly secreted via the T2SS. Although the precursor of TDH is targeted to the Sec pathway, a fraction of mature TDH was observed to re-enter the bacterial cytoplasm. The N terminus of mature TDH comprises a T3SS signal sequence, allowing it to be loaded into the T3SS. We also show that T3SS-delivered TDH as an effector contributes to intestinal fluid accumulation in a rabbit diarrhoeal model of V. parahaemolyticus infection. Thus, our results show that an unconventional export mechanism for a bacterial toxin via the T3SS in tandem with the Sec machinery facilitates the virulence trait of V. parahaemolyticus.
AB - Many Gram-negative pathogens utilize dedicated secretion systems to export virulence factors such as exotoxins and effectors 1–4 . Several exotoxins are synthesized as precursors containing amino-terminal Sec signal peptides and are exported through the inner-membrane-bound Sec machinery to the periplasm, followed by secretion across the outer membrane to the exterior using a type II secretion system (T2SS) 3,5 . Here, we report that thermostable direct haemolysin (TDH), an exotoxin of the food-borne pathogen Vibrio parahaemolyticus, can be exported through the type III secretion system (T3SS), which engages in one-step secretion of effectors 4 , despite possessing a Sec signal peptide and being mainly secreted via the T2SS. Although the precursor of TDH is targeted to the Sec pathway, a fraction of mature TDH was observed to re-enter the bacterial cytoplasm. The N terminus of mature TDH comprises a T3SS signal sequence, allowing it to be loaded into the T3SS. We also show that T3SS-delivered TDH as an effector contributes to intestinal fluid accumulation in a rabbit diarrhoeal model of V. parahaemolyticus infection. Thus, our results show that an unconventional export mechanism for a bacterial toxin via the T3SS in tandem with the Sec machinery facilitates the virulence trait of V. parahaemolyticus.
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U2 - 10.1038/s41564-019-0368-y
DO - 10.1038/s41564-019-0368-y
M3 - Letter
C2 - 30778145
AN - SCOPUS:85061729397
VL - 4
SP - 781
EP - 788
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 5
ER -