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- Vibrio vulnificus PlpA facilitates necrotic host cell death induced by the pore forming MARTX toxin
- Changyi Cho , Sanghyeon Choi , Myung Hee Kim , Byoung Sik Kim
- J. Microbiol. 2022;60(2):224-233. Published online February 1, 2022
- DOI: https://doi.org/10.1007/s12275-022-1448-x
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- 7 Web of Science
- 6 Crossref
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Abstract
- Opportunistic pathogen Vibrio vulnificus causes severe systemic infection in humans with high mortality. Although multiple exotoxins have been characterized in V. vulnificus, their interactions and potential synergistic roles in pathogen-induced host cell death have not been investigated previously. By employing a series of multiple exotoxin deletion mutants, we investigated whether specific exotoxins of the pathogen functioned together to achieve severe and rapid necrotic cell death. Human epithelial cells treated with V. vulnificus with a plpA deletion background exhibited an unusually prolonged cell blebbing, suggesting the importance of PlpA, a phospholipase A2, in rapid necrotic cell death by this pathogen. Additional deletion of the rtxA gene encoding the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin did not result in necrotic cell blebs. However, if the rtxA gene was engineered to produce an effector-free MARTX toxin, the cell blebbing was observed, indicating that the pore forming activity of the MARTX toxin is sufficient, but the MARTX toxin effector domains are not necessary, for the blebbing. When a recombinant PlpA was treated on the blebbed cells, the blebs were completely disrupted. Consistent with this, MARTX toxin-pendent rapid release of cytosolic lactate dehydrogenase was significantly delayed in the plpA deletion background. Mutations in other exotoxins such as elastase, cytolysin/hemolysin, and/or extracellular metalloprotease did not affect the bleb formation or disruption. Together, these findings indicate that the pore forming MARTX toxin and the phospholipase A2, PlpA, cooperate sequentially to achieve rapid necrotic cell death by inducing cell blebbing and disrupting the blebs, respectively.
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Citations
Citations to this article as recorded by
- Genome-wide phenotypic profiling of transcription factors and identification of novel targets to control the virulence of Vibrio vulnificus
Dayoung Sung, Garam Choi, Minji Ahn, Hokyung Byun, Tae Young Kim, Hojun Lee, Zee-Won Lee, Ji Yong Park, Young Hyun Jung, Ho Jae Han, Sang Ho Choi
Nucleic Acids Research.2024;[Epub] CrossRef - Vibrio-infecting bacteriophages and their potential to control biofilm
Ana Cevallos-Urena, Jeong Yeon Kim, Byoung Sik Kim
Food Science and Biotechnology.2023; 32(12): 1719. CrossRef -
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Future Microbiology.2023; 18(6): 373. CrossRef - Functional conservation of specialized ribosomes bearing genome-encoded variant rRNAs in Vibrio species
Younkyung Choi, Eunkyoung Shin, Minho Lee, Ji-Hyun Yeom, Kangseok Lee, Bashir Sajo Mienda
PLOS ONE.2023; 18(12): e0289072. CrossRef - Complex regulatory networks of virulence factors in Vibrio vulnificus
Garam Choi, Sang Ho Choi
Trends in Microbiology.2022; 30(12): 1205. CrossRef - MARTX toxin of Vibrio vulnificus induces RBC phosphatidylserine exposure that can contribute to thrombosis
Han Young Chung, Yiying Bian, Kyung-Min Lim, Byoung Sik Kim, Sang Ho Choi
Nature Communications.2022;[Epub] CrossRef
- Genome-wide phenotypic profiling of transcription factors and identification of novel targets to control the virulence of Vibrio vulnificus
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