Difference between revisions of "Necrotizing fasciitis induced by Vibrio vulnificus"

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[2] Oliver J.D. 2005. Wound infections caused by Vibrio vulnificus and other  
 
[2] Oliver J.D. 2005. Wound infections caused by Vibrio vulnificus and other  
marine bacteria . Epidemiol. Infect. 133: 383–391.
+
marine bacteria. Epidemiol. Infect. 133: 383–391. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870261/
  
 
[3] Vibrio vulnificus | Vibrio Illness (Vibriosis) | CDC. CDC [Internet]. 2013. Available  
 
[3] Vibrio vulnificus | Vibrio Illness (Vibriosis) | CDC. CDC [Internet]. 2013. Available  
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[4] Vezzulli, L. et al. 2013. Ocean warming and spread of pathogenic vibrios in the  
 
[4] Vezzulli, L. et al. 2013. Ocean warming and spread of pathogenic vibrios in the  
aquatic environment. Microb Ecol. 65: 817-825.
+
aquatic environment. Microb Ecol. 65: 817-825. http://link.springer.com/article/10.1007%2Fs00248-012-0163-2
  
 
[5] Horseman M, Surani S. 2011. A comprehensive review of Vibrio vulnificus:  
 
[5] Horseman M, Surani S. 2011. A comprehensive review of Vibrio vulnificus:  
an important cause of severe sepsis and skin and soft-tissue infection. International Journal of Infectious Diseases 15:e157–e166.
+
an important cause of severe sepsis and skin and soft-tissue infection. International Journal of Infectious Diseases 15:e157–e166. http://www.sciencedirect.com/science/article/pii/S1201971210025385
  
 
[6]Hor L., et al. 2000. Mechanism of high susceptibility of iron-overloaded mouse to  
 
[6]Hor L., et al. 2000. Mechanism of high susceptibility of iron-overloaded mouse to  
Vibrio vulnificus infection. Microbiol Immunol 44:871–8.
+
Vibrio vulnificus infection. Microbiol Immunol 44:871–8. https://www.jstage.jst.go.jp/article/mandi1977/44/11/44_11_871/_article
  
 
[7]Lee J.H., et al. 2007. Identification and characterization of the Vibrio vulnificus  
 
[7]Lee J.H., et al. 2007. Identification and characterization of the Vibrio vulnificus  
rtxA essential for cytotoxicity in vitro and virulence in mice. J Microbiol 45:146–52.
+
rtxA essential for cytotoxicity in vitro and virulence in mice. J Microbiol 45:146–52. http://www.msk.or.kr/jsp/view_old_journalD.jsp?paperSeq=2520
  
 
[8] Jones MK, Oliver JD. 2009. Vibrio vulnificus: disease and pathogenesis. Infect  
 
[8] Jones MK, Oliver JD. 2009. Vibrio vulnificus: disease and pathogenesis. Infect  
Immun 77:1723–33.
+
Immun 77:1723–33. http://iai.asm.org/content/77/5/1723.full
  
 
[9] Kim, S. Y., et al. 2003. Regulation of Vibrio vulnificus virulence by the LuxS  
 
[9] Kim, S. Y., et al. 2003. Regulation of Vibrio vulnificus virulence by the LuxS  
quorum-sensing system. Mol. Microbiol. 48:1647-1664.
+
quorum-sensing system. Mol. Microbiol. 48:1647-1664. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.2003.03536.x/full
  
 
[10]Matsuoka Y, et al. 2013. Accurate diagnosis and treatment of Vibrio  
 
[10]Matsuoka Y, et al. 2013. Accurate diagnosis and treatment of Vibrio  
vulnificus infection: a retrospective study of 12 cases. Braz J Infect Dis 17:7–12.
+
vulnificus infection: a retrospective study of 12 cases. Braz J Infect Dis 17:7–12. http://www.sciencedirect.com/science/article/pii/S141386701200219X
  
 
[11] Hong G-L, et al. 2012. Surgical treatment of 19 cases with Vibrio  
 
[11] Hong G-L, et al. 2012. Surgical treatment of 19 cases with Vibrio  
necrotising fasciitis. Burns 38:290–295.
+
necrotising fasciitis. Burns 38:290–295. http://www.sciencedirect.com/science/article/pii/S0305417911001380
  
 
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Revision as of 05:55, 15 April 2014

This student page has not been curated.

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 [1]. 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.

Figure 1. Colorized SEM of a flagellated Vibrio vulnificus bacterium; Mag. 26367x. Image from CDC Public Health Image Library. http://phil.cdc.gov/Phil/details.asp

While Vibrio vulnificus is one of the more infrequent causes of NF, it has a relatively high mortality rate of 26% [2] 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[3]. There also appears to be increasing incidence of Vibrios infections, which could be the result of ocean warming due to global climate change [4].

Pathogenesis

Toxins involved

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 [5]. Iron is believed to promote infection by enhancing growth of the bacteria and reducing immune response [6].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.

  • VvRtxA appears to be the key toxin that contributes to the cytotoxicity of the bacteria. It is believed to trigger excessive production of reactive oxygen species (ROS) (ROS) by the host, resulting in necrotic cell death and apoptosis, which is programmed cell death [7].
  • 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 [8].
  • 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 [8].

Quorum Sensing

Figure 2. Levels of the RtxA1 toxin (green) in V. vulnificus increased in a time-dependent manner after making contact with the host cells. From Young, R.M., et al. 2007. Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells. Cellular Microbiology 10:848-862. Copywrite © 2007 The Authors http://onlinelibrary.wiley.com/doi/10.1111/j.1462-5822.2007.01088.x/citedby

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 [9]. 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 [8]. 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

Figure 3. Presentations of skin damage of vibrio necrotizing fasciitis including A. swelling and vein dilation, B. bruising, C. blistering, and D. tissue necrosis. From Hong G-L, et al. 2012. Surgical treatment of 19 cases with Vibrio necrotising fasciitis. Burns 38:290–295. Copyright © 2012 Elsevier Ltd and ISBI http://www.sciencedirect.com/science/article/pii/S0305417911001380

Symptoms tend to appear in the summer months, when the seawater temperature rises resulting in increased V. vulnificus presence [10]. 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%[5]. 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 Options

Treatment can vary from relatively noninvasive antibiotics to amputation of infected tissue and limbs.

Further Reading

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.

References

[1] Davis C. 2012. Necrotizing Fasciitis (Flesh-Eating Disease) Symptoms, Treatment, Causes, Pictures, Diagnosis. MedicineNet [Internet]. Available from: http://www.medicinenet.com/necrotizing_fasciitis/article.htm

[2] Oliver J.D. 2005. Wound infections caused by Vibrio vulnificus and other marine bacteria. Epidemiol. Infect. 133: 383–391. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870261/

[3] Vibrio vulnificus | Vibrio Illness (Vibriosis) | CDC. CDC [Internet]. 2013. Available from: http://www.cdc.gov/vibrio/vibriov.html

[4] Vezzulli, L. et al. 2013. Ocean warming and spread of pathogenic vibrios in the aquatic environment. Microb Ecol. 65: 817-825. http://link.springer.com/article/10.1007%2Fs00248-012-0163-2

[5] Horseman M, Surani S. 2011. A comprehensive review of Vibrio vulnificus: an important cause of severe sepsis and skin and soft-tissue infection. International Journal of Infectious Diseases 15:e157–e166. http://www.sciencedirect.com/science/article/pii/S1201971210025385

[6]Hor L., et al. 2000. Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection. Microbiol Immunol 44:871–8. https://www.jstage.jst.go.jp/article/mandi1977/44/11/44_11_871/_article

[7]Lee J.H., et al. 2007. Identification and characterization of the Vibrio vulnificus rtxA essential for cytotoxicity in vitro and virulence in mice. J Microbiol 45:146–52. http://www.msk.or.kr/jsp/view_old_journalD.jsp?paperSeq=2520

[8] Jones MK, Oliver JD. 2009. Vibrio vulnificus: disease and pathogenesis. Infect Immun 77:1723–33. http://iai.asm.org/content/77/5/1723.full

[9] Kim, S. Y., et al. 2003. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system. Mol. Microbiol. 48:1647-1664. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.2003.03536.x/full

[10]Matsuoka Y, et al. 2013. Accurate diagnosis and treatment of Vibrio vulnificus infection: a retrospective study of 12 cases. Braz J Infect Dis 17:7–12. http://www.sciencedirect.com/science/article/pii/S141386701200219X

[11] Hong G-L, et al. 2012. Surgical treatment of 19 cases with Vibrio necrotising fasciitis. Burns 38:290–295. http://www.sciencedirect.com/science/article/pii/S0305417911001380

Edited by (Elana Goldstein), a student of Nora Sullivan in BIOL168L (Microbiology) in The Keck Science Department of the Claremont Colleges Spring 2014.