Vibrio vulnificus: Disease and Pathogenesis

Vibrio vulnificus is an opportunistic human pathogen that is highly lethal and is responsible for the overwhelming majority of reported seafood-related deaths in the United States (30, 117).This bacterium is a part of the natural flora of coastal marine environments worldwide and has been isolated from water, sediments, and a variety of seafood, including shrimp, fish, oysters, and clams (4,7,25,26,43,97, 109, 116, 118, 149, 165).Consumption of seafood (primarily raw oysters) containing V. vulnificus can result in a severe, fulminant systemic infection.Characteristics of this disease include fever, chills, nausea, hypotensive septic shock, and the formation of secondary lesions on the extremities of patients (11,22,41,74, 115, 146).This primary septicemia is the most lethal infection caused by V. vulnificus, with an average mortality rate exceeding 50% (30,41).A review of 459 U.S. cases reported by the FDA between 1992 and 2007 (J.D. Oliver, unpublished) revealed that 51.6% of the patients died.Interestingly, 85.6% of the cases were male; this aspect of the infection is discussed later in this review.Of 180 cases in 2002 to 2007 for which FDA data were available, 92.8% of patients had consumed raw oysters prior to the onset of symptoms and 95.3% had some preexisting disease(s).The latter are clearly associated with V. vulnificus infection, with liver diseases, such as cirrhosis or hepatitis, being the most common (116).In addition to septicemia, V. vulnificus can produce serious wound infections that typically result from exposure of open wounds to water harboring the bacterium (114).Wound infections are frequently contracted as a result of recreational swimming, fishing injuries, or seafood handling (7,46).Like systemic disease, wound infections progress rapidly to cellulitis, ecchymoses, and bullae, which can progress to necrotizing fasciitis at the site of infection; however, the mortality rate for wound infections (ca.25%) is lower than that for systemic disease (10,13,74).This organism possesses a wide array of virulence factors, including acid neutralization, capsular polysaccharide expression, iron acquisition, cytotoxicity, motility, and expression of proteins involved in attachment and adhesion.These factors likely require concerted expression for pathogenesis to take place and appear to be under the control of global regulators.Overall, V. vulnificus is a complex microorganism with physiological characteristics that contribute to its survival in the marine environment and in the human host. BIOTYPES AND GENOTYPESBiotypes.Strains of V. vulnificus are classified into biotypes based on their biochemical characteristics.Strains belonging to biotype 1 are responsible for the majority of human infections, while biotype 2 strains are primarily eel pathogens (2, 153).A recently identified third biotype (biotype 3) was shown to possess biochemical properties of both biotypes 1 and 2 and to cause human wound infection (7).Analyses comparing genomic similarities among the three biotypes indicated that biotype 3 is a hybrid of biotypes 1 and 2 (6).Furthermore, the use of multilocus sequence typing indicated similar results and divided strains of V. vulnificus into genetic lineages ( 24).This analysis also uncovered the presence of a 33-kb genomic island found only in lineage 1/biotype 1 strains (24).Several genes located within this genomic island are thought to play a role in pathogenesis of other pathogens; therefore, it was suggested that V. vulnificus strains possessing this island also possess an increased potential for virulence (24).While biotype 3 does cause human infections, these have to date been limited to Israel and to persons handling tilapia fish, and biotype 1 is the predominant cause of human infections.Thus, the remainder of this review will focus on the characteristics of biotype 1.On average, 34 cases of V. vulnificus infection are reported annually by the U.S. .However, in recent years this number has risen dramatically.The CDC reported Vibrio infections increased by 78% between 1996 and 2006, and in 2005, 121 cases of V. vulnificus disease were confirmed (14,15).While reasons for these increases have yet to be determined, it has been noted that outbreaks of V. vulnificus disease in Israel are associated with record high temperatures (124).These data suggest that global climate change resulting in higher water temperatures may increase the frequency of V. vulnificus disease and influence the global distribution of this pathogen (124).Despite increases in the number of cases, the rate of infection remains relatively low.This contrasts with the ubiquity of this organism in marine habitats.At least part of the explanation for this difference is that V. vulnificus rarely causes severe disease in healthy individuals.However, persons with underlying disorders, such as chronic liver disease, diabetes, hemachromatosis, AIDS, malignancy, and immunocompromised states, are at high risk of infection (74, 115, 116).In fact, individuals with compromised immune systems or chronic liver disease are up to 80 times more likely than healthy individuals to develop primary septicemia (13).However, in that such underlying conditions put between 12 million and 30 million Americans at