Reduced virulence of the MARTX toxin increases the persistence of outbreak-associated Vibrio vulnificus in host reservoirs
| Autor: | Jungwon Hwang, Myung Hee Kim, Sanghyeon Choi, Byoung Sik Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Models Molecular DUF1 domain of unknown function Virulence Factors infectious disease cysteine protease domain Bacterial Toxins Virulence Vibrio vulnificus medicine.disease_cause Biochemistry virulence factor Virulence factor MARTX multifunctional autoprocessing repeats-in-toxin Microbiology ABH the alpha/beta hydrolase domain CPD cysteine protease domain 03 medical and health sciences Mice Bacterial Proteins medicine Animals Humans MCF makes caterpillars floppy-like Molecular Biology ARF ADP-ribosylation factor CD circular dichroism ExoY ExoY-like adenylate cyclase domain 030102 biochemistry & molecular biology biology Toxin Effector RID Rho GTPase-inactivation domain Cell Biology biology.organism_classification Cysteine protease Vibrio MARTX toxin 030104 developmental biology effector Vibrio Infections hpi hours postinfection Host-Pathogen Interactions DmX domain X effector Bacteria Research Article HeLa Cells |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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