The U.S. has seen a rise in infections caused by so-called “flesh-eating bacteria,” a.k.a. Vibrio vulnificus, a bacterium that inhabits brackish water. But is this microbe really “eating” flesh? How does it cause the damage it does—and why? 

What's in a Name?

Like other Vibrio species, V. vulnificus lives in coastal estuarine waters and is commonly associated with shellfish, such as oysters. In the context of human health, the bacterium is most known for causing gastrointestinal disease that can advance to septicemia in people who have ingested raw or undercooked shellfish that harbors the organism. However, this sea-dwelling microbe can also wreak havoc on the body surface.

If someone with an open wound (e.g., a recent tattoo or cut) comes in contact with V. vulnificus, the microbe may enter and infect said wound. What might start as swelling and pain at the wound site can, within a few days, lead to widespread skin destruction, making it appear as if something has been munching the flesh away. 

However, this isn’t quite accurate. Rather, V. vulnificus triggers wound infections that can advance to necrotizing fasciitis (NF), a condition characterized by death of the muscle fascia (connective tissue surrounding muscle fibers and other body structures) and tissues below the skin. As the infection progresses, the skin eventually breaks down too, giving rise to blistering and gaping lesions. If not treated quickly via antimicrobial therapy and surgery to remove necrotic tissues (debridement), V. vulnificus can become systemic, particularly in hosts with certain preexisting conditions (e.g., liver disease), and prove fatal.

“Time is critical—you have to get antibiotic treatment right away,” said James Oliver, Ph.D., a professor emeritus at University of North Carolina Charlotte who has studied V. vulnificus for over 45 years. “A lot of times people [with wound infections] see it [and think it] looks like spider bite or something; they don't pay much attention to it. And then 24 hours later, they go into the hospital because [they now have] bullous lesions."

Though it has captured headlines in recent months, V. vulnificus is not the only bacterium to cause NF, nor is it the most common. For example, while V. vulnificus causes 150-200 cases in the U.S. every year, group A Streptococcus (GAS)—another “flesh-eater” that inhabits the skin, nose and throat of humans and spreads via respiratory droplets or contaminated surfaces—has caused approximately 700-1,150 infections annually since 2010.

That could change, though. As climate change boosts temperatures of coastal waters, which promotes growth of V. vulnificus (blooms of the organism usually occur between May and October when the water is warmest) and broadens its geographic range, infections caused by the bacterium are expected to rise. Already, cases in the eastern U.S. increased 8-fold between 1988 and 2018, emphasizing the need to understand and raise awareness about this sea-faring microbe.

How Does V. vulnificus Destroy Flesh?

Despite years of study, how V. vulnificus causes soft tissue infections is still a bit of a mystery. While the bacterium does have an arsenal of known and putative virulence factors, most studies have focused on their role in causing gastroenteritis and subsequent septicemia. According to Oliver, this attention is likely due to the differences in mortality between the wound and gut infections (~20% for wound infections and 50% for ingestion).

What is known is that tissue destruction is tied to a repertoire of proteases, hemolysins, collagenases, toxins and other proteins secreted by, or associated with, the bacterium. Some of these factors are better understood than others. For example, RtxA1—a toxin secreted by V. vulnificus and implicated in both gastrointestinal and wound infections—kills cells by altering host cytoskeleton and actin aggregation; it also antagonizes phagocytic immune cells. Capsule (a sticky extracellular coating) is essential for V. vulnificus, due to its ability to resist host immune responses and promote bacterial survival. Adhesion factors (for sticking to tissues), flagella (which allows the bacterium to move and proliferate at the site of infection) and the ability to engage in chemotaxis (a process that facilitates invasion into deeper tissues), also appear to be involved.

V. vulnificus bacteria are not the sole perpetrators of NF progression—host factors are also at play. Indeed, immune cells that control infection, like neutrophils, can also exacerbate disease through the release of inflammatory compounds. The nutritional milieu provided by the host further influences disease susceptibility and outcomes. For instance, V. vulnificus is an iron-hungry microbe—the ability to acquire iron is integral for its survival and plays an important role in its pathogenesis. Thus, the bacterium is more likely to spread beyond a wound site in people with serum iron-elevating conditions, such as those with liver disease, leading to deadly systemic infection. 

Still, for Oliver there is much to be elucidated about V. vulnificus pathogenesis and wound infections. “I’d like to know more about the actual toxins involved,” he said, highlighting that wounds present a vastly different environment from the gut, where most V. vulnificus virulence research has centered.

Why Does V. vulnificus "Eat" Flesh?

Why does any microbe cause destruction in (or on) a host? From a bacterial standpoint, the factors that disrupt host cells are likely, in some way, helping the microbe itself. It is also important to consider that humans are not the natural host for V. vulnificus. The microbe is ubiquitous in coastal waters, often in association with shellfish—it evolved to thrive in these environments. Thus, if it finds itself in a human wound, V. vulnificus deploys its pre-existing repertoire of tools to survive. Whether that repertoire contains the tools needed to successfully infect the human host varies depending on the strain of the bacterium. In any case, tissue destruction is an unfortunate outcome of the bacterial cells using what they already possess to make do in the host environment they are in.

Perhaps a better question then is how does V. vulnificus benefit from destroying host tissue? There are several elements to consider. For one, damaged tissue may serve as a source of food for V. vulnificus. “Tissue destruction [releases] all kinds of proteins, lipids [and] so many [other] things, which the bacteria could use as nutrients,” Oliver said. While the use of tissue-derived nutrients has not been explicitly shown for V. vulnificus, the use of nutrients released from host cells during infection has been illustrated for pathogens like V. cholerae (a relative of V. vulnificus) and GAS, another NF-causing organism. 

The ability of V. vulnificus to spread to deeper tissues—and thus cause further destruction—may also be nutritionally beneficial for the bacterium, allowing for migration into fresh nutrient pools to minimize competition. Factors that kill host cells protect V. vulnificus from immune responses geared toward terminating it, further enhancing its survival. For the most part, however, what V. vulnificus ‘gets’ out of infection requires more investigation.

Protect Your Flesh

For all the intrigue behind the how and why underlying V. vulnificus wound infections and NF, one thing is clear: it is best to avoid them in the first place. The U.S. Centers for Disease Control and Prevention (CDC) recommends that those with open wounds avoid brackish water, including wading at the beach. If avoidance is not possible, washing wounds with soap after contacting water potentially harboring V. vulnificus, or raw/undercooked seafood, is a good idea.

Oliver highlighted that awareness about V. vulnificus is key. “I think the best thing is to [make people] aware, especially if they have underlying diseases,” he said, which puts them at greater risk for infection. “[If] they get a cut while they're in the water, and it becomes infected, they should immediately go to a doctor, and they should mention that they got a cut while they were in sea water to try to ring a bell for the physician.” He noted that V. vulnificus is “extremely sensitive to antibiotics,” which is a good thing—it’s just matter of catching the infection early. 

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Learn more about Vibrio vulnificus (and other Vibrio species) in this episode of MicroTalk featuring Dr. Salvador Almagro-Moreno.