Reduced virulence of the MARTX toxin increases the persistence of outbreak-associated Vibrio vulnificus in host reservoirs
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Choi, Sanghyeon; Hwang, Jungwon; Kim, Myung Hee] Korea Res Inst Biosci & Biotechnol KRIBB, Metab Regulat Res Ctr, Infect & Immun Res Lab, Daejeon, South Korea; [Choi, Sanghyeon] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon, South Korea; [Kim, Byoung Sik] Ewha Womans Univ, Dept Food Sci & Engn, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183444
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.jbc.2021.100777
초록/요약
Opportunistic bacteria strategically dampen their virulence to allow them to survive and propagate in hosts. However, the molecular mechanisms underlying virulence control are not clearly understood. Here, we found that the opportunistic pathogen Vibrio vulnificus biotype 3, which caused an outbreak of severe wound and intestinal infections associated with farmed tilapia, secretes significantly less virulent multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, which is the most critical virulence factor in other clinical Vibrio strains. The biotype 3 MARTX toxin contains a cysteine protease domain (CPD) evolutionarily retaining a unique autocleavage site and a distinct beta-flap region. CPD autoproteolytic activity is attenuated following its autocleavage because of the beta-flap region. This beta-flap blocks the active site, disabling further autoproteolytic processing and release of the modularly structured effector domains within the toxin. Expression of this altered CPD consequently results in attenuated release of effectors by the toxin and significantly reduces the virulence of V. vulnificus biotype 3 in cells and in mice. Bioinformatic analysis revealed that this virulence mechanism is shared in all biotype 3 strains. Thus, these data provide new insights into the mechanisms by which opportunistic bacteria persist in an environmental reservoir, prolonging the potential to cause outbreaks.
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