Vibrio vulnificus infection in patients with liver disease: report of five autopsy cases

Chen, Yongxin; Satoh, Toshimi; Tokunaga, Osamu

doi:10.1007/s00428-002-0613-1

Cited by 25 publications

(22 citation statements)

References 15 publications

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“…V . vulnificus infection [9, 16, 37]. This damage has subsequently been attributed to the additive function of secreted exotoxins VvhA and MARTX [16].…”

Section: Resultsmentioning

confidence: 99%

“…vulnificus intragastric (i.g.) infection, it might follow that the MARTX toxin repeat region pore, sufficient for cellular necrosis in vitro , would be sufficient for MARTX-associated intestinal damage, bacterial dissemination, and death as linked to colonization of the liver and spleen [9, 16, 37–39]. Yet, the effector domain region is retained across V .…”

Section: Introductionmentioning

confidence: 99%

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The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine

2017

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Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin’s central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs–a key step in V. vulnificus foodborne pathogenesis–even before onset of overt intestinal pathology.

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“…V . vulnificus infection [9, 16, 37]. This damage has subsequently been attributed to the additive function of secreted exotoxins VvhA and MARTX [16].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine

2017

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“…Bacterial translocation may explain how enteric bacteria become the source of infection in other organs, such as in fasciitis [11]. Chen et al [12] reported that autopsy examination of patients with V. vulnificus infection and liver dysfunction revealed portal hypertension and gastrointestinal mucosal changes. Thus, bacteria invading the fascia from the intestine by bacterial translocation, with bacterial virulence factors, may play a pathogenic role in soft-tissue infection.…”

Section: Discussionmentioning

confidence: 98%

Clinical features of Vibrio vulnificus infections in the coastal areas of the Ariake Sea, Japan

Matsumoto

Ohshige

Fujita

et al. 2010

Journal of Infection and Chemotherapy

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“…A recent study from Korea is the first to report significant increases in the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6 in serum from V. vulnificus-infected patients compared to healthy individuals, confirming a role for dysregulation of the cytokine response (39). Autopsy reports from Japanese V. vulnificus cases also show a widespread inflammatory response characterized by a generalized neutrophil influx (3).…”

mentioning

confidence: 97%

Inflammatory Cytokine Response to Vibrio vulnificus Elicited by Peripheral Blood Mononuclear Cells from Chronic Alcohol Users Is Associated with Biomarkers of Cellular Oxidative Stress

et al. 2003

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Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1␤ (IL-1␤), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. Vibrio vulnificus is a gram-negative bacterium found commonly in marine and estuarine environments. In the United States, it predominates in the warm waters of the Gulf and Atlantic Coasts (25, 27, 28). Despite not being a notifiable disease, each year there are 20 to 50 reported cases of V. vulnificus primary septicemia in the United States, occurring most often following the consumption of naturally contaminated raw oysters (2, 14). V. vulnificus also has the ability to cause gastroenteritis, which is generally self-limiting, and wound infections in otherwise healthy individuals (17, 32). Primary septicemia is seen almost exclusively in people with an underlying condition affecting their immune system. In epidemiological studies, primary septicemia caused by V. vulnificus is most often associated with preexisting liver disease, although other conditions, such as diabetes mellitus, hemochromatosis, immunodeficiency, or malignancy, may also increase susceptibility to this organism (2,14,17,24,41). The impairment of iron metabolism and resultant iron overload associated with many of these conditions is thought to support increased V. vulnificus growth and reduced immune clearance (1, 15, 16). Primary septicemia caused by V. vulnificus appears to follow a classical septic shock pathway, including an overwhelming inflammatory cytokine response followed by multiorgan failure and death. Presently, there is no effective treatment for V. vulnificus once someone has developed primary septicemia, and death usually ensues. It should be noted that V. vulnificus has many similarities with other gram-negative, encapsulated, opportunistic bacterial pathogens and likely exploits similar host susceptibility pathways that could be targeted for intervention.To date, the majority of V. vulnificus studies have focused on the bacterial factors involved in disease (41). Therefore, while much is now known about some of the bacterial factors involved in the disease process, little is understood about host cellular factors leading to susceptibility. It has been previously shown that V. vulnificus has the ability to elicit inflammationassociated cytokines from primary human cells in vitro and from animals...

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Vibrio vulnificus infection in patients with liver disease: report of five autopsy cases

Cited by 25 publications

References 15 publications

The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine

The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine

Clinical features of Vibrio vulnificus infections in the coastal areas of the Ariake Sea, Japan

Inflammatory Cytokine Response to Vibrio vulnificus Elicited by Peripheral Blood Mononuclear Cells from Chronic Alcohol Users Is Associated with Biomarkers of Cellular Oxidative Stress

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