Protein Toxins of Pathogenic Vibrio Species

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 8892

Special Issue Editor


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Guest Editor
Department of Microbiology and Immunology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY 14642, USA
Interests: pathogenesis of Vibrio spp.; gene expression; cytotoxicity; T3SS; toxins

Special Issue Information

Dear Colleagues,

The study of pathogenic Vibrio species is historically rooted in the biochemical characterization of cholera toxin, the major virulence factor associated with the human pathogen V. cholerae. Over several decades, the field has grown to appreciate that the Vibrio genus encompasses numerous species having diverse toxigenic activities targeting humans and marine life, varying from fish to crustaceans and corals. In addition to cholera toxin, the hemolysins, cytotoxins, and various other toxins produced by Vibrio continue to teach us about host-cell homeostatic processes and how pathogen subversion leads to disease. We have also seen exciting investigations into the genetic basis of toxigenicity, virulence-factor regulation, pandemic epidemiology, and multiple-secretion systems that we now know can deliver protein toxins to both prokaryotic and eukaryotic targets. Every time we look further, we find another Vibrio secret that was awaiting our discovery.

This Special Issue of Toxins will highlight the breadth and depth of the activities of toxins produced by Vibrio species. In addition, we recognize that important findings in one species have facilitated detailed and comparative studies of related proteins and functions. We welcome contributions describing toxins from any pathogenic Vibrio species, and those that showcase a cross-disciplinary understanding of how the marine-based Vibrio genus acquires, regulates, and deploys an arsenal of toxins to cause diverse diseases across a wide range of hosts.

Dr. Michelle Dziejman
Guest Editor

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Keywords

  • Vibrio spp.
  • cytotoxin
  • hemolysin
  • cholera toxin
  • effector protein
  • MARTX
  • Vibrio pathogenesis

Published Papers (3 papers)

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Research

18 pages, 4014 KiB  
Article
In Vitro and In Vivo Inhibitory Activities of Selected Traditional Medicinal Plants against Toxin-Induced Cyto- and Entero- Toxicities in Cholera
by Rajitha Charla, Priyanka P. Patil, Arati A. Bhatkande, Nisha R. Khode, Venkanna Balaganur, Harsha V. Hegde, Darasaguppe R. Harish and Subarna Roy
Toxins 2022, 14(10), 649; https://doi.org/10.3390/toxins14100649 - 20 Sep 2022
Cited by 2 | Viewed by 1756
Abstract
Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by [...] Read more.
Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by toxins secreted by Vibrio cholerae. Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of V. cholerae were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of P. granatum were tested against CT-induced elevation of cAMP levels in CHO cell line, binding of CT to ganglioside GM1 receptor and NMDCY-induced cytotoxicity. Significant reduction of cAMP levels in CFCF treated CHO cell line was observed for all extracts except P. longum. C. arborea, P. granatum, H. antidysenterica and A. marmelos showed >50% binding inhibition of CT to GM1 receptor. C. arborea, P. granatum, and P. guajava effectively decreased cytotoxicity and morphological alterations caused by NMDCY in CHO cell line. Further, the efficacy of these three plants against CFCF-induced enterotoxicity was seen in adult mice ligated-ileal loop model as evidenced by decrease in volume of fluid accumulation, cAMP levels in ligated-ileal tissues, and histopathological changes in intestinal mucosa. Therefore, these plants can be further validated for their clinical use against cholera. Full article
(This article belongs to the Special Issue Protein Toxins of Pathogenic Vibrio Species)
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13 pages, 2666 KiB  
Article
Metal Ions and Chemical Modification Reagents Inhibit the Enzymatic Activity of Lecithin-Dependent Hemolysin from Vibrio parahaemolyticus
by Francisco Javier Vazquez-Armenta, Uriel Felipe Valdez-Olmos, Aldo Alejandro Arvizu-Flores, Jesus Fernando Ayala-Zavala, Adrian Ochoa-Leyva and Alonso Alexis Lopez-Zavala
Toxins 2022, 14(9), 609; https://doi.org/10.3390/toxins14090609 - 1 Sep 2022
Cited by 1 | Viewed by 1652
Abstract
Lecithin-dependent thermolabile hemolysin (LDH) is a virulence factor excreted by Vibrio parahaemolyticus, a marine bacterium that causes important losses in shrimp farming. In this study, the function of LDH was investigated through its inhibition by metal ions (Mg2+, Ca2+ [...] Read more.
Lecithin-dependent thermolabile hemolysin (LDH) is a virulence factor excreted by Vibrio parahaemolyticus, a marine bacterium that causes important losses in shrimp farming. In this study, the function of LDH was investigated through its inhibition by metal ions (Mg2+, Ca2+, Mn2+, Co2+, Ni2+ and Cu2+) and chemical modification reagents: β-mercaptoethanol (βME), phenylmethylsulfonyl fluoride (PMSF) and diethyl pyrocarbonate (DEPC). LDH was expressed in the Escherichia coli strain BL-21, purified under denaturing conditions, and the enzymatic activity was evaluated. Cu2+, Ni2+, Co2+ and Ca2+ at 1 mmol/L inhibited the LDH esterase activity by 20–95%, while Mg2+ and Mn2+ slightly increased its activity. Additionally, PMSF and DEPC at 1 mmol/L inhibited the enzymatic activity by 40% and 80%, respectively. Dose-response analysis showed that DEPC was the best-evaluated inhibitor (IC50 = 0.082 mmol/L), followed by Cu2+ > Co2+ > Ni2+ and PMSF (IC50 = 0.146–1.5 mmol/L). Multiple sequence alignment of LDH of V. parahaemolyticus against other Vibrio species showed that LDH has well-conserved GDSL and SGNH motifs, characteristic of the hydrolase/esterase superfamily. Additionally, the homology model showed that the conserved catalytic triad His-Ser-Asp was in the LDH active site. Our results showed that the enzymatic activity of LDH from V. parahaemolyticus was modulated by metal ions and chemical modification, which could be related to the interaction with catalytic amino acid residues such as Ser153 and/or His 393. Full article
(This article belongs to the Special Issue Protein Toxins of Pathogenic Vibrio Species)
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12 pages, 1471 KiB  
Article
A Potent Inhibitor of the Cystic Fibrosis Transmembrane Conductance Regulator Blocks Disease and Morbidity Due to Toxigenic Vibrio cholerae
by Fabian Rivera-Chávez, Bradley T. Meader, Sinan Akosman, Vuk Koprivica and John J. Mekalanos
Toxins 2022, 14(3), 225; https://doi.org/10.3390/toxins14030225 - 18 Mar 2022
Cited by 7 | Viewed by 4548
Abstract
Vibrio cholerae uses cholera toxin (CT) to cause cholera, a severe diarrheal disease in humans that can lead to death within hours of the onset of symptoms. The catalytic activity of CT in target epithelial cells increases cellular levels of 3′,5′-cyclic AMP (cAMP), [...] Read more.
Vibrio cholerae uses cholera toxin (CT) to cause cholera, a severe diarrheal disease in humans that can lead to death within hours of the onset of symptoms. The catalytic activity of CT in target epithelial cells increases cellular levels of 3′,5′-cyclic AMP (cAMP), leading to the activation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical ion channel that transports chloride out of epithelial cells, resulting in an electrolyte imbalance in the intestinal lumen and massive water loss. Here we report that when administered perorally, benzopyrimido-pyrrolo-oxazinedione, (R)-BPO-27), a potent small molecule inhibitor of CFTR, blocked disease symptoms in a mouse model for acute diarrhea caused by toxigenic V. cholerae. We show that both (R)-BPO-27 and its racemic mixture, (R/S)-BPO-27, are able to protect mice from CT-dependent diarrheal disease and death. Furthermore, we show that, consistent with the ability of the compound to block the secretory diarrhea induced by CT, BPO-27 has a measurable effect on suppressing the gut replication and survival of V. cholerae, including a 2010 isolate from Haiti that is representative of the most predominant ‘variant strains’ that are causing epidemic and pandemic cholera worldwide. Our results suggest that BPO-27 should advance to human Phase I studies that could further address its safety and efficacy as therapeutic or preventative drug intervention for diarrheal syndromes, including cholera, that are mediated by CFTR channel activation. Full article
(This article belongs to the Special Issue Protein Toxins of Pathogenic Vibrio Species)
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