Reduced virulence of the MARTX toxin increases the persistence of outbreak-associated Vibrio vulnificus in host reservoirs

Sanghyeon Choi, Byoung Sik Kim, Jungwon Hwang, Myung Hee Kim

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1 Scopus citations

Abstract

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 β-flap region. CPD autoproteolytic activity is attenuated following its autocleavage because of the β-flap region. This β-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.

Original languageEnglish
Article number00570
JournalJournal of Biological Chemistry
Volume296
DOIs
StatePublished - 1 Jan 2021

Bibliographical note

Funding Information:
Funding and additional information—This work was supported by the Ministry of Science and Information and Communications Technology (ICT) of Korea (2014R1A2A1A01005971 and 2017R1A2B3007317 to M. H. K.) and the KRIBB Initiative Program (KGM2112133 to M. H. K.).

Publisher Copyright:
© 2021 THE AUTHORS.

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