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''Vibrio vulnificus'' is a species of
Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
, motile, curved rod-shaped (bacillus), pathogenic
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
of the genus ''
Vibrio ''Vibrio'' is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to survive ...
''. Present in marine environments such as
estuaries An estuary is a partially enclosed coastal body of brackish water with one or more rivers or streams flowing into it, and with a free connection to the open sea. Estuaries form a transition zone between river environments and maritime environme ...
, brackish ponds, or coastal areas, ''V. vulnificus'' is related to '' ''V. cholerae'''', the causative agent of
cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...
. At least one strain of ''V. vulnificus'' is
bioluminescent Bioluminescence is the production and emission of light by living organisms. It is a form of chemiluminescence. Bioluminescence occurs widely in marine vertebrates and invertebrates, as well as in some fungi, microorganisms including some b ...
. Infection with ''V. vulnificus'' leads to rapidly expanding
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
or
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. It was first isolated as a source of disease in 1976.


Signs and symptoms

''Vibrio vulnificus'' is an extremely virulent bacterium that can cause three types of infections: * Acute
gastroenteritis Gastroenteritis, also known as infectious diarrhea and gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydr ...
from eating raw or undercooked shellfish: ''V. vulnificus'' causes an infection often incurred after eating
seafood Seafood is any form of sea life regarded as food by humans, prominently including fish and shellfish. Shellfish include various species of molluscs (e.g. bivalve molluscs such as clams, oysters and mussels, and cephalopods such as octopus an ...
, especially raw or undercooked oysters. It does not alter the appearance, taste, or odor of oysters. Symptoms include vomiting,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
, and abdominal pain. *
Necrotizing Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
wound infections can occur in injured skin exposed to contaminated marine water. ''V. vulnificus'' bacteria can enter the body through open
wound A wound is a rapid onset of injury that involves lacerated or punctured skin (an ''open'' wound), or a contusion (a ''closed'' wound) from blunt force trauma or compression. In pathology, a ''wound'' is an acute injury that damages the epider ...
s when swimming or wading in infected waters, or by puncture wounds from the spines of fishes such as
stingray Stingrays are a group of sea rays, which are cartilaginous fish related to sharks. They are classified in the suborder Myliobatoidei of the order Myliobatiformes and consist of eight families: Hexatrygonidae (sixgill stingray), Plesiobatidae ...
s. People may develop a
blister A blister is a small pocket of body fluid ( lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing ( friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...
ing
dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved c ...
sometimes mistaken for
pemphigus Pemphigus ( or ) is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes. The name is derived from the Greek root ''pemphix'', meaning "pustule". In pemphigus, autoantibodies form against desmoglein, whic ...
or
pemphigoid Pemphigoid is a group of rare autoimmune blistering diseases of the skin, and mucous membranes. As its name indicates, pemphigoid is similar in general appearance to pemphigus, but, unlike pemphigus, pemphigoid does not feature acantholysis, a ...
. * Invasive
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
can occur after eating raw or undercooked shellfish, especially oysters. ''V. vulnificus'' is 80 times more likely to spread into the bloodstream in people with compromised
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
s, especially those with chronic liver disease. When this happens, severe symptoms including blistering skin lesions and
septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...
can sometimes lead to death. This severe infection may occur regardless of whether the infection began from contaminated food or an open wound. Among healthy people, ingestion of ''V. vulnificus'' can cause vomiting, diarrhea, and abdominal pain. In someone with a compromised immune system, particularly those with chronic
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...
, it can infect the bloodstream, causing a severe and life-threatening illness characterized by fever and chills, decreased blood pressure (septic shock), and blistering skin lesions. While men have been shown to be more at risk from this infection than women, co-morbidities such as alcoholic cirrhosis and diseases affecting the endocrine system (diabetes, rheumatoid arthritis, etc.) put a person far more at risk to develop infection from ''V. vulnificus.''


Pathogenesis

Capsule: V. ''vulnificus'' has a capsule, made of polysaccharides, and is thought to protect against
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
. The capsule also aids the bacteria in escaping opsonization. Different strains of the bacteria are capable of shifting through the unencapsulated and encapsulated forms. Mouse models have shown that the unencapsulated forms are avirulent. These same strains however, are shown to have a higher predisposition to shift to the virulent encapsulated form when taken up by oysters. Endotoxin: Like all gram negative bacteria, V. ''vulnificus'' has LPS (
lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O- antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the out ...
as the major component of its outer membrane). However, the LPS the bacteria produces isn't as efficient at triggering the immune system's release of tumor necrosis factor (TNF) alpha and other cytokines that produce shock syndromes. The capsular proteins the bacteria express however, are capable of producing an immune response contributing to shock syndrome. Exotoxin: ''V. vulnificus'' produces a number of extracellular toxins such as metalloprotease VvpE, cytolysin/hemolysin VvhA, and the
multifunctional autoprocessing repeats-in-toxin The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein seq ...
s (MARTX) toxin. While the VvhA and MARTX toxin are factors in the bacteria's virulence, in vivo studies in mice suggest that the MARTX toxin is more responsible for bacterial dissemination from the intestine to produce sepsis. Iron: Growth of V. ''vulnificus'' is dependent on the amount of iron that is accessible to the bacteria. The observed association of the infection with liver disease (associated with increased serum iron) might be due to the capability of more virulent strains to capture iron bound to
transferrin Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encod ...
.Oxford handbook of Infect Dis and Microbiol, 2009


Strains

The most harmful strains of ''V. vulnificus'' documented have been observed in three different forms. The first is in an anti-phagocytic polysaccharide capsule that protects the bacteria. By encapsulating the bacteria, phagocytosis and opsonization are not able to occur, thus allowing the bacteria to continue throughout the organism it is in. The second way that ''V. vulnificus'' has been most harmful is with some of the toxins that it creates. These toxins are not part of the infection that ''V. vulnificus'' causes but instead they are part of a secondary infection in the GI tract that most certainly will lead to systemic infection. Lastly, ''V. vulnificus'' has been seen to cause more harm in patients who have higher levels of iron.


Treatment

''Vibrio vulnificus'' wound infections have a mortality rate around 25%. In people in whom the infection worsens into sepsis, typically following ingestion, the mortality rate rises to 50%. The majority of these people die within the first 48 hours of infection. The optimal treatment is not known, but in one retrospective study of 93 people in Taiwan, use of a third-generation
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
and a
tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...
(e.g.,
ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and join ...
and
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus ...
, respectively) was associated with an improved outcome. Prospective clinical trials are needed to confirm this finding, but ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' data support the suggestion that this combination is
synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christia ...
against ''V. vulnificus''. Likewise, the
American Medical Association The American Medical Association (AMA) is a professional association and lobbying group of physicians and medical students. Founded in 1847, it is headquartered in Chicago, Illinois. Membership was approximately 240,000 in 2016. The AMA's sta ...
and the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) recommend treating the person with a
quinolone Quinolone may refer to: * 2-Quinolone * 4-Quinolone * Quinolone antibiotic A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They a ...
or
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
doxycycline with ceftazidime. The first successful documented treatment of
fulminant Fulminant () is a medical descriptor for any event or process that occurs suddenly and escalates quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. The word comes from Latin ''fulmināre'', to stri ...
''V. vulnificus''
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
was in 1995. Treatment was ceftazidime and intravenous (IV)
ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...
and IV doxycycline, which proved successful. Prevention of secondary infections from
respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
and
acute renal failure Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are c ...
is crucial. Key to the diagnosis and treatment were the early recognition of bullae in an immunocompromised person with
liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
and oyster ingestion within the previous 48 hours, and the request by the physician for STAT Gram staining and
blood culture A blood culture is a medical laboratory test used to detect bacteria or fungi in a person's blood. Under normal conditions, the blood does not contain microorganisms: their presence can indicate a bloodstream infection such as bacteremia ...
s for ''V. vulnificus''. ''Vibrio vulnificus'' often causes large, disfiguring
ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
s that require extensive
debridement Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy. I ...
or even amputation.


Prognosis

''Vibrio vulnificus'' is the most common cause of death due to seafood in the United States, causing over 95% of deaths that are known to have occurred due to ingested seafood. If treatment with tetracycline or other cephalosporin antibiotics is initiated at the onset of symptoms and the full course followed, patients generally experience no long term effects. The worst prognosis is in those people arriving at hospital in a state of
shock Shock may refer to: Common uses Collective noun *Shock, a historic commercial term for a group of 60, see English numerals#Special names * Stook, or shock of grain, stacked sheaves Healthcare * Shock (circulatory), circulatory medical emerge ...
. Total mortality in treated people (ingestion and wound) is around 33%. People especially vulnerable are those with liver disease (especially
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
and
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
) or
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
states (some kinds of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, bone marrow suppression, HIV,
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, etc.). With these cases, ''V. vulnificus'' usually enters the bloodstream, where it may cause fever and chills, septic shock (with sharply decreased blood pressure), and blistering skin lesions. About half of those who contract blood infections die. ''Vibrio vulnificus'' infections also disproportionately affect males; 85% of those developing endotoxic shock from the bacteria are male. Females having had an
oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), historically also called ''ovariotomy'' is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference ...
experienced increased mortality rates, as
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
has been shown experimentally to have a protective effect against ''V. vulnificus''.


Epidemiology

''Vibrio vulnificus'' is commonly found in the
Gulf of Mexico The Gulf of Mexico ( es, Golfo de México) is an ocean basin and a marginal sea of the Atlantic Ocean, largely surrounded by the North American continent. It is bounded on the northeast, north and northwest by the Gulf Coast of the United ...
, where more than a dozen people have died from the infection since 1990. Most deaths at that time were occurring due to fulminant sepsis, either in the area of oyster harvest and ingestion, or in tourists returning home. Lack of disease recognition, and also of the risk factors, presentation, and cause, were and are major obstacles to good outcome and recovery. After the successful treatment of the first person, the
Florida Department of Health The Florida Department of Health is responsible for protecting the public health and safety of the residents and visitors of the state of Florida. It is a cabinet-level agency of the state government, headed by a state surgeon general who reports ...
was able to trace the origin of the outbreak to
Apalachicola Bay Apalachicola may refer to: * Apalachicola people, a group of Native Americans who lived along the Apalachicola River in present-day Florida Places * Apalachicola, Florida *Apalachicola River * Apalachicola Bay * Apalachicola National Forest * Apa ...
oysters and their harvesting in water prone to excessive growth of the organism. This contamination was due to warmth of the water and change in freshwater dilution because of a change in flow of the
Chattahoochee River The Chattahoochee River forms the southern half of the Alabama and Georgia border, as well as a portion of the Florida - Georgia border. It is a tributary of the Apalachicola River, a relatively short river formed by the confluence of the Chatt ...
into the
Apalachicola River The Apalachicola River is a river, approximately 160 mi (180 km) long in the state of Florida. The river's large watershed, known as the ACF River Basin, drains an area of approximately into the Gulf of Mexico. The distance to its far ...
, and in turn into Apalachicola Bay. A similar situation occurred after
Hurricane Katrina Hurricane Katrina was a destructive Category 5 Atlantic hurricane that caused over 1,800 fatalities and $125 billion in damage in late August 2005, especially in the city of New Orleans and the surrounding areas. It was at the time the cost ...
in
New Orleans New Orleans ( , ,New Orleans
.


Further treatment research

While the treatment for ''V. vulnificus'' can be as straightforward as making the rapid choice of appropriate antibiotics, there have been cases in which the genes mutated, thus rendering antibiotics ineffective. While looking for an answer to this problem, researchers found that one way to stop the infection from spreading is to again mutate the bacteria. This mutation happens on the flagellum of the bacteria. When injected with flgC and flgE (two genes in the flagella that cause the mutation), the flagellum no longer function properly. When unable to move normally, the bacteria is no longer able to spread toxins through the body, thus decreasing the effect that ''V. vulnificus'' has on the body systemically.


History

The pathogen was first isolated in 1976 from a series of blood culture samples submitted to the CDC in
Atlanta Atlanta ( ) is the capital and most populous city of the U.S. state of Georgia. It is the seat of Fulton County, the most populous county in Georgia, but its territory falls in both Fulton and DeKalb counties. With a population of 498,7 ...
. It was described as a "lactose-positive vibrio". It was subsequently given the initial name, ''Beneckea vulnifica'', and finally, ''Vibrio vulnificus'', by J. J. Farmer in 1979. Increasing seasonal temperatures and decreasing coastal salinity levels seem to favor a greater concentration of ''Vibrio'' within filter-feeding shellfish of the U.S. Atlantic seaboard and the Gulf of Mexico, especially oysters (''
Crassostrea virginica The eastern oyster (''Crassostrea virginica'')—also called the Atlantic oyster, American oyster, or East Coast oyster—is a species of true oyster native to eastern North and South America. Other names in local or culinary use include the We ...
''). Scientists have frequently demonstrated the presence of ''V. vulnificus'' in the gut of oysters and other shellfish and in the intestines of fish that inhabit oyster reefs. The vast majority of people who develop sepsis from ''V. vulnificus'' became ill after they ate raw oysters; most of these cases have been men. In 2005, health officials clearly identified strains of ''V. vulnificus'' infections among evacuees from
New Orleans New Orleans ( , ,New Orleans
due to the flooding there caused by Hurricane Katrina. In 2015, in Florida, eight cases of ''V. vulnificus'' infection with two resulting in death were reported. In 2022 following
Hurricane Ian Hurricane Ian was a large and destructive List of Category 4 Atlantic hurricanes, Category 4 Atlantic hurricane that was the deadliest Tropical cyclone, hurricane to strike the U.S. state, state of Florida since the 1935 Labor Day hurricane. Ia ...
,
Lee County, Florida Lee County is located in Southwest Florida on the Gulf Coast. As of the 2020 census, the population was 760,822. The county seat is Fort Myers (with a population of 86,395 as of the 2020 census), and the largest city is Cape Coral with an est ...
saw a sharp rise in infections and deaths from ''V. vulnificus''. By October 18, 2022, four deaths and 29 illnesses had been recorded since landfall of the hurricane in late September.


Natural transformation

Natural transformation In category theory, a branch of mathematics, a natural transformation provides a way of transforming one functor into another while respecting the internal structure (i.e., the composition of morphisms) of the categories involved. Hence, a natur ...
is a
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
l adaptation for DNA transfer between individual cells. ''V. vulnificus'' was found to become naturally transformable during growth on
chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...
in the form of crab shells. The ability to now carry out transformation experiments in the laboratory should facilitate
molecular genetic Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
analysis of this opportunistic
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
.


References


External links


Large and detailed article on ''V. vulnificus'' at ''Todar's Online Textbook of Bacteriology''

CNN video on vibrio vulnificus

Type strain of ''Vibrio vulnificus'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q135183 Bacterial diseases Bacterium-related cutaneous conditions Vibrionales Waterborne diseases Bacteria described in 1976 Marine microorganisms