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Bacteriology at UW- Madison |
Vibrio vulnificus is scarcely recognized by many microbiologists, much less by the public at risk for the disease it causes. Yet, in this country, the bacterium causes 95 percent of all seafood-related deaths, and it causes a disease with a mortality rate greater than that of any other bacterial infection.
Vibrio vulnificus is a Gram-negative, motile curved bacterium found in marine and estuarine environments. It has been isolated from seawater, sediments, plankton and shellfish (oysters, clams and crabs) located in the Gulf of Mexico, the Atlantic Coast as far north as Cape Cod, and the entire U.S. West Coast. The bacterium thrives in warm seawater and is part of a group of vibrios that are referred to as "halophiles", because they require salt for growth. Vibrio vulnificus is frequently found in oysters and other shellfish in warm coastal waters during the summer months. This correlates with the peak incidence of disease caused by the bacterium.
Vibrio vulnificus is in the Bacterial family Vibrionaceae, same as Vibrio cholerae, the agent of epidemic cholera in humans. Vibrios are one of the most common organisms in surface waters of the world. They occur in both marine and freshwater habitats and in associations with aquatic animals. Some species are bioluminescent and live in mutualistic associations with fish and other marine life. Other species are pathogenic for fish, eels, and frogs, as well as other vertebrates and invertebrates.
V. cholerae and V. parahaemolyticus are pathogens of humans. Both produce diarrhea, but in ways that are entirely different. V. parahaemolyticus is an invasive organism affecting primarily the colon; V. cholerae is noninvasive, affecting the small intestine through secretion of an enterotoxin.
Vibrio vulnificus is an emerging pathogen of humans. It causes wound infections, gastroenteritis, or a syndrome known as primary septicemia. It was first recognized as an agent of disease in 1976. The first documented case of disease caused by the bacterium was in 1979.
Figure 1. Vibrio
vulnificus
is
a typical marine vibrio - a slightly curved bacterium, motile by means
of a single polar flagellum. Note that this cell is in the very early
stages
of cell division.The nuclear (light staining) material has been
replicated
and is being moved towards opposite poles of the cell, and the new
cross
wall (septum) that will separate the progeny cells is beginning to form
at the vertical midline of the cell.
Disease
V. vulnificus causes disease in individuals who eat contaminated seafood (usually raw or undercooked oysters) or have an open wound that is exposed to seawater. Among healthy people, ingestion of V. vulnificus can cause vomiting, diarrhea, and abdominal pain. Most V. vulnificus infections are acute and have no long-term consequences.
In immunocompromised persons, particularly those with chronic liver disease, V. vulnificus can invade the bloodstream from either a wound or from the GI tract, causing a severe and life-threatening illness called primary septicemia, characterized by fever, chills, septic shock and death. Blistering skin lesions accompany the disease in about 70% of the cases. V. vulnificus bloodstream infections are fatal about 50% of the time.
Although V. vulnificus is a rare cause of disease, it is likely that it is unrecognized and underreported (one estimate of the total number of cases annually in the U.S. is as high as 45,000). Between 1988 and 1995, CDC received reports of over 300 V. vulnificus infections from the Gulf Coast states, where the majority of cases occur.
Persons who are immunocompromised, especially those with chronic liver disease, are at risk for V. vulnificus when they eat raw seafood, particularly oysters. These individuals are 80-200 times more likely to develop V. vulnificus primary septicemia than are healthy people. For this particular risk group, the infection carries one of the highest mortality rates of all bacterial infections.
Health conditions that place a person at risk for serious illness or death from V. vulnificus infection include liver disease, hemochromatosis, diabetes, stomach problems, kidney disease, cancer, immune disorders (including HIV) and long-term steroid use. In these individuals, the bacterium enters the blood stream, resulting in septic shock, rapidly followed by death in many cases. These individuals are strongly advised not to consume raw or inadequately cooked seafood. Many of these health conditions may exist but be unrecognized in a person, so that they do not realize they are at risk of V. vulnificus disease.
Pathogenesis
Wound infections result from contaminating an existing open wound with seawater harboring the organism, or by cutting part of the body on coral, fish, fishhooks, etc., followed by contamination with the organism.
Also, people who consume foods contaminated with this organism are susceptible to gastroenteritis, which usually develops within 16 hours of eating the contaminated food. They experience vomiting, diarrhea, and abdominal pain. Many patients develop distinctive bullous skin lesions.
The bacterium invades directly from the GI tract or broken skin to
produce
bacteremia and septicemia. Invasion is characterized by the occurrence
of blister-like skin lesions or bullae, and rapidly-spreading necrosis
resembling necrotizing fasciitis.
Figure 2.
A.Characteristic
skin lesions associated with Vibrio vulnificus infection on the
leg in a 75-year-old patient with liver cirrhosis in whom septic shock
and bacteremia developed. B V. vulnificus bacteremia developed
one
day after a fish bone injury on the fourth finger of the left hand
(arrow)
in a 45-year-old patient with uremia. C. Gram-negative curved
bacilli
isolated from a blood sample of the 45-year-old patient with
uremia.(Photos
from Hsueh, et al. Vibrio vulnificus in Taiwan..CDC Emerging
Infectious
Diseases Volume 10, Number 8, August 2004)
Ecology and Virulence
Ecology and virulence are intertwined in this bacterium. it lives in a free-swimming planktonic form in bays and estuaries, but it is able to colonize oysters and apparently other fish and shellfish as well. It can also colonize human tissues, and invade from tissues into the bloodstream where it can resist host defenses and cause a lethal septicemia.
Attempts to associate phenotypic or genotypic characteristics of Vibrio vulnificus with strain virulence have been largely unsuccessful. V. vulnificus exhibits considerable strain-to-strain variation in virulence. More than 100 steains of the bacterium have been identified and it is possible that many thousands more exist. The bacterium also exhibits a large number of potential determinants of virulence, on the order of V. cholerae and Pseudomonas aeruginosa combined, but thier role in disease has not been elucidated.
There are at least three ways that Vibrio vulnificus strains have been divided into two "biotypes", one of which is pathogenic for humans, and the other of which is found in shellfish or fish, or is free-living. One way is based on the difference in a 17-bp nucleotide sequence of the 16S rRNA gene. By this criterion two major groups of V. vulnificus have been identified, designated types A and B. The majority of nonclinical isolates are type A, and there is a positive correlation between the type B genotype and the cause of human disease. Similarly, a homogeneous LPS type is found in vibrios that live in associations with eels (biotype 2), and disinct heterogenous LPS types are observed in clinical isolates (Biotype 1). And while the presence of a capsule occurs in virulent strains, noncapsulated strains are nonvirulent. The significance of these observations is not known and they do not explain how the bacteria are able to switch from free-swimming and colonizimg oysters to colonizing human tissues.
Generalized Stress Response
Many of the heat shock proteins produced by V. vulnificus, such
as the chaperonins DnaK and GroEL, and the proteases, Clp and
Lon,
are induced by environmental changes other than increased temperature,
such as ethanol, heavy metals or oxidizing agents, high osmolarity,
pollutants,
starvation, exposure to low temperature, or interaction with eukaryotic
hosts. This is thought to be a generalized stress response in the
bacterium. Through a process termed cross protection, this
response
improves the bacterium's thermotolerance, salt tolerance, tolerance to
heavy metals and UV exposure, and starvation survival. The generalized
stress response may be critical for bacterial adaptation to changes in
the environment, and is a major link between bacterial ecology
and
bacterial pathogenesis.
Stress is also thought to cause genomic differences observed among strains of V. vulnificus. Genomic differences may be the result of gene rearrangements in the bacterium. Since the bacterium may exist in a rapidly changing ecosystem where major alterations in temperature, salt concentration, UV irradiation, and nutrient availability are routinely encountered, it is possible that such gene rearrangements may increase the chances of survival of the bacterium when it moves from water to oyster to human.
Capsule
Expression of a polysaccharide capsule is necessary for virulence of
Vibrio
vulnificus. The noncapsulated form is nonvirulent. Under
laboratory
conditions, acapsular variants arise at a fairly high frequency
(~1/100),
with certain environmental stresses dramatically increasing this switch
rate. Once such noncapsulated (translucent) colonies arise, they
do not appear able to revert back to the capsule-expressing (opaque)
morphology.
The mechanism of this capsule switching has not been explained.
Fimbriae
Type IV pili (fimbriae) are required for virulence. Type IV pili are
N-methylphenylalanine pili, characteristic of vibrios, that allow the
bacteria
to adhere to epithelial cells. The receptor has not yet been
identified.
The N-methylphenylalanine pili of Vibrio cholerae utilize
N-acetylneuraminic
acid (sialic acid) as a receptor.
Figure 3. Electron micrograph
of Vibrio vulnificus. The arrows mark fimbriae (pili) of the
bacterium.
The laboratory of Dr. Mark Strom at the
NOAA Northwest Fisheries Science Center is
studying how the adhesins of the bacterium, which include fimbriae and
other cell surface components, influence the course of mammalian
colonization
and infection, as well as the organism's ability to colonize and
persist
in shellfish.
LPS
As a Gram negative bacterium, V. vulnificus lipopolysaccharide
(endotoxin) is expected to play a role in fever and septic shock
brought
on by infection. On the basis of lipopolysaccharide (LPS) antigens, the
species can be organized into three biotypes. Biotype 1 is the
predominant
human pathogen; biotype 2 is associated with eels; and biotype 3 was
recently
isolated from fish handlers in Israel. Biotype 2 consists of a
homogeneous
type of LPS, and although Biotype 1 was originally divided into 5
antigenic subgroups, other subgroups are known to exist. Biotype 1 is
almost
invariably associated with human disease, and one particular LPS type
(1/5)
is significantly more prevalent among clinical strains. This suggests
that
either the presence of this LPS type itself causes increased virulence,
or that the LPS type is a marker of more virulent strains.
Besides attachment ability, capsule switching, LPS, and the ability to undergo the stress response, other properties of V. vulnificus that have been considered as determinants of virulence include production of alternate (stress) sigma factors, SSR repeats, motility, quorum sensing, production of a siderophore and a hemolysin (cytolysin), and numerous extracellular enzymes, including proteases, collagenase, mucinase, esterase, chondroitinase, hyaluronidase, DNAase and sulfatase.
A recently identified determinant of virulence in Vibrio vulnificus is the member of the RTX family of toxins produced by a limited group of Gram-negative pathogens. RTX toxins cause pore formation in red blood cells, necrotic death of Hep2 cells, and depolymerization of actin in HeLa cells.
An excellent review of the molecular pathogenesis of Vibrio vulnificus may be seen at Gulig, et al. Molecular Pathogenesis of Vibrio vulnificus
Treatment
Antibiotics are necessary for treatmeent of V. vulnificus
infections.
Effective antibiotics include tetracycline, third-generation
cephalosporins
(e.g., ceftazidime), and imipenem. In case of wound infection,
aggressive
debridement is necessary to remove necrotic tissue.
For more information on Vibrio vulnificus
CDC
- General Information
CDC
- Technical Information
FDA/CFSAN
Bad Bug Book
FDA/CFSAN Prime
Connection
Clemson
University
Florida
State University - Vibrio vulnificus
Florida
State Ubiversity - Toward Safer Oysters
NOAA
Northwest Fisheries Science Center
Southern
Medical
Association Vibrio vulnificus
Infection: case study
UNC Charlotte
- Oliver Research Lab