Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition
ABSTRACT Vibrio vulnificus is an environmental organism that causes septic human infections characterized by high morbidity and mortality. The annual incidence and global distribution of this pathogen are increasing as ocean waters warm. Clinical strains exhibit variations in the primary virulence t...
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American Society for Microbiology
2017
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oai:doaj.org-article:ee6fe3842b084e09add14ee746ab3a0d2021-11-15T15:22:05ZVariable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition10.1128/mSphereDirect.00272-172379-5042https://doaj.org/article/ee6fe3842b084e09add14ee746ab3a0d2017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00272-17https://doaj.org/toc/2379-5042ABSTRACT Vibrio vulnificus is an environmental organism that causes septic human infections characterized by high morbidity and mortality. The annual incidence and global distribution of this pathogen are increasing as ocean waters warm. Clinical strains exhibit variations in the primary virulence toxin, suggesting a potential for the emergence of new strains with altered virulence properties. A clonal outbreak of tilapia-associated wound infections in Israel serves as a natural experiment for the sudden emergence of a new V. vulnificus strain. The effector domain content of the multifunctional autoprocessing RTX (MARTX) toxin of the outbreak-associated biotype 3 (BT3) strains was previously shown to harbor a modification generated by recombination. The modification introduced an actin-induced adenylate cyclase effector domain (ExoY) and an effector domain that disrupts the Golgi organelle (DmX). Here, we report that the exchange of these effector domains for a putative progenitor biotype 1 toxin arrangement produces a toxin that slows the lysis kinetics of targeted epithelial cells but increases cellular rounding phenotypes in response to bacteria. In addition, replacing the biotype 3 toxin variant with the putative progenitor biotype 1 variant renders the resulting strain significantly more virulent in mice. This suggests that the exchange of MARTX effector domains during the emergence of BT3 generated a toxin with reduced toxin potency, resulting in decreased virulence of this outbreak-associated strain. We posit that selection for reduced virulence may serve as a route for this lethal infectious agent to enter the human food chain by allowing it to persist in natural hosts. IMPORTANCE Vibrio vulnificus is a serious infection linked to climate change. The virulence capacity of these bacteria can vary by gene exchange, resulting in new variants of the primary virulence toxin. In this study, we tested whether the emergence of an epidemic strain of V. vulnificus with a novel toxin variant correlated with a change in virulence. We found that restoring the biotype 3 toxin variant to the putative progenitor-type toxin resulted in dramatically increased virulence, revealing that the emergence of the biotype 3 strain could be linked to virulence reduction. This reduced virulence, previously found also in the biotype 1 strain, suggests that reduced virulence may stimulate outbreaks, as strains have greater capacity to enter the human food chain through reduced impact to environmental hosts.Byoung Sik KimHannah E. GavinKarla J. F. SatchellAmerican Society for Microbiologyarticlebiotype 3MARTXVibrio vulnificuscytotoxinsmouserecombinationMicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017) |
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biotype 3 MARTX Vibrio vulnificus cytotoxins mouse recombination Microbiology QR1-502 |
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biotype 3 MARTX Vibrio vulnificus cytotoxins mouse recombination Microbiology QR1-502 Byoung Sik Kim Hannah E. Gavin Karla J. F. Satchell Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
description |
ABSTRACT Vibrio vulnificus is an environmental organism that causes septic human infections characterized by high morbidity and mortality. The annual incidence and global distribution of this pathogen are increasing as ocean waters warm. Clinical strains exhibit variations in the primary virulence toxin, suggesting a potential for the emergence of new strains with altered virulence properties. A clonal outbreak of tilapia-associated wound infections in Israel serves as a natural experiment for the sudden emergence of a new V. vulnificus strain. The effector domain content of the multifunctional autoprocessing RTX (MARTX) toxin of the outbreak-associated biotype 3 (BT3) strains was previously shown to harbor a modification generated by recombination. The modification introduced an actin-induced adenylate cyclase effector domain (ExoY) and an effector domain that disrupts the Golgi organelle (DmX). Here, we report that the exchange of these effector domains for a putative progenitor biotype 1 toxin arrangement produces a toxin that slows the lysis kinetics of targeted epithelial cells but increases cellular rounding phenotypes in response to bacteria. In addition, replacing the biotype 3 toxin variant with the putative progenitor biotype 1 variant renders the resulting strain significantly more virulent in mice. This suggests that the exchange of MARTX effector domains during the emergence of BT3 generated a toxin with reduced toxin potency, resulting in decreased virulence of this outbreak-associated strain. We posit that selection for reduced virulence may serve as a route for this lethal infectious agent to enter the human food chain by allowing it to persist in natural hosts. IMPORTANCE Vibrio vulnificus is a serious infection linked to climate change. The virulence capacity of these bacteria can vary by gene exchange, resulting in new variants of the primary virulence toxin. In this study, we tested whether the emergence of an epidemic strain of V. vulnificus with a novel toxin variant correlated with a change in virulence. We found that restoring the biotype 3 toxin variant to the putative progenitor-type toxin resulted in dramatically increased virulence, revealing that the emergence of the biotype 3 strain could be linked to virulence reduction. This reduced virulence, previously found also in the biotype 1 strain, suggests that reduced virulence may stimulate outbreaks, as strains have greater capacity to enter the human food chain through reduced impact to environmental hosts. |
format |
article |
author |
Byoung Sik Kim Hannah E. Gavin Karla J. F. Satchell |
author_facet |
Byoung Sik Kim Hannah E. Gavin Karla J. F. Satchell |
author_sort |
Byoung Sik Kim |
title |
Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
title_short |
Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
title_full |
Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
title_fullStr |
Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
title_full_unstemmed |
Variable Virulence of Biotype 3 <named-content content-type="genus-species">Vibrio vulnificus</named-content> due to MARTX Toxin Effector Domain Composition |
title_sort |
variable virulence of biotype 3 <named-content content-type="genus-species">vibrio vulnificus</named-content> due to martx toxin effector domain composition |
publisher |
American Society for Microbiology |
publishDate |
2017 |
url |
https://doaj.org/article/ee6fe3842b084e09add14ee746ab3a0d |
work_keys_str_mv |
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