Necrotizing fasciitis induced by Vibrio vulnificus
Necrotizing fasciitis (NF) is a soft-tissue infection that is most commonly caused by bacteria that infect open wounds and results in tissue damage and death. For this reason the bacteria that induce this infection are termed “flesh-eating bacteria”. Different variations of Necrotizing fasciitis exist and they are separated into three general groups based on the types of bacteria that cause the infection . The first and most common are the Streptococcus and Staphylococcus bacteria, which are of growing concern because of the emergence of MRSA’s. The second group involves polymicrobial-induced infection or infection by Vibrio vulnificus. Clostridium bacteria cause the third variation of Necrotizing fasciitis.
While Vibrio vulnificus is one of the more infrequent causes of NF, it has a relatively high mortality rate of 26%  because it spreads quickly and it is hard to diagnose. V. vulnificus thrives in warm, medium salinity water and causes infections either through the ingestion of contaminated seafood or in this case, through open wounds that come in contact with V. vulnificus contaminated water. There also appears to be increasing incidence of Vibrios infections, which could be the result of ocean warming due to global climate change .
The people most at risk for infection are those with immunodeficiencies, especially liver disease, hepatitis B or C or any disorder characterized by high iron levels . Iron is believed to promote infection by enhancing growth of the bacteria and reducing immune response .V. vulnificus uses cytotoxins i.e. compound that are toxic to cells, to cause the infection. A few mechanisms of V. vulnificus cytotoxicity resulting in tissue damage have been studied in mice, including the toxins VvTtxA, hemolysin (Vvha), and VvpE.
- Hemolysin (VvhA) is an exotoxin encoded by the bacteria, which assists in iron release from hemoglobin. The toxin also causes cell death by pore formation in the cellular membrane .
- VvpE is an extracellular metalloprotease and its purified form has been shown to cause tissue necrosis and bullous lesions, which are characteristic of NF caused by V. vulnificus. VvpE degrades type IV collagen, which is a structural component of basement membranes, and it also activates procaspase 3, which is a protein involved in cellular apoptosis .
Cell-to-cell contact with the host is required for cytotoxicity (Figure 2) and V. vulnificus knows when to release its toxins using quorum sensing . LuxS synthesizes the autoinducer and LuxR is the transcriptional regulator. Mutation of either of the genes that codes these proteins resulted in decreased cytotoxicity. The gene luxS influences the transcription of vvhA and vvpE, resulting in increased or decreased levels of these toxins. The protein HlyU also regulates cytotoxicity . The gene hlyU regulates the expression of rtxA at the transcriptional level by binding upstream of the rtxA promoter region, initiating transcription.
Symptoms and Diagnosis
Symptoms tend to appear in the summer months, when the seawater temperature rises resulting in increased V. vulnificus presence . Early symptoms come across as the flu: fever, diarrhea, and nausea. Within 12-24 hours after infection, patients develop severe cellulitis with tissue swelling and hemorrhagic bullae and many become septic, which can increase the mortality rate from about 25% to a staggering 50-75%. Some characteristic symptoms of this infection include vasodilation and edema (swelling). This can be explained by the presence of the toxin Hemolysin, which can form pores in the endothelial cells of blood vessels [8, 12]. It induces histamine to be released from mast cells and it activates kinin pathways. The later and more extreme symptom of necrotic cell death is associated with the toxin RtxA, which causes depolymerization of actin in cells and apoptosis.
Many of the patients also experience a change in mental status, such as lethargy and disorientation [5, 11]. Unfortunately because the infection acts so quickly, and can be misdiagnosed as the flu or a less dangerous skin infection, it is difficult to treat effectively. Knowing whether the patient has come into contact with the ocean recently is the most significant indicator of whether it is Vibrio induced NF, followed by whether the patient has any form of immunodifficiency.
Treatment can vary from relatively noninvasive antibiotics to amputation of infected tissue and limbs.
As mentioned in the introduction, it appears that Vibrio caused infections are increasing in incidence and researchers believe that this increase is related to global warming.
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Edited by (Elana Goldstein), a student of Nora Sullivan in BIOL168L (Microbiology) in The Keck Science Department of the Claremont Colleges Spring 2014.