Cashew compound
may help to fight superbug

Published October 03 2016

Neutrophil extracellular traps are sticky webs of DNA (colored green in this artistic rendering) that trap and kill bacteria (blue). IMAGE COURTESY OF VICTOR NIZET

Since the 1940s, antibiotics have revolutionized the treatment of bacterial infections and greatly reduced illness and death from infectious diseases. However, the widespread use of antibiotics has led to the emergence of “superbugs” that are resistant to first-line treatments and, in some cases, to all available antibiotics. In a recent paper published in the Journal of Biological Chemistry, Victor Nizet of the University of California, San Diego, and colleagues showed that a compound from cashews could boost the immune system to kill drug-resistant bacteria.

According to the Centers for Disease Control and Prevention, there are more than 2 million cases of antibiotic-resistant bacterial infection in the U.S. each year, leading to more than 23,000 deaths. Among the most serious threats is methicillin-resistant Staphylococcus aureus, or MRSA, a leading cause of health care-acquired infections. To combat the growing threat of antibiotic resistance, scientists are hunting for new classes of antibiotics and immune-boosting drugs, often drawing candidates from the natural world.

A team of researchers headed by Nizet has identified an immune-boosting compound with MRSA-killing potential in extracts of cashew nut shells. Cashew nut and leaf extracts have been used as a traditional remedy for inflammation, ulcers and cancer but haven’t been demonstrated to be effective in clinical trials. The active compound, anacardic acid, previously was shown to have direct antimicrobial activity.

The team of scientists found that anacardic acid provides a double boost to the function of immune cells called neutrophils, which are the body’s first line of defense against bacterial infection. First, anacardic acid triggers neutrophils to release reactive oxygen species, which are toxic to bacteria, in a sudden “oxidative burst.” In addition, anacardic acid stimulates neutrophils to release neutrophil extracellular traps, or NETs, which are sticky webs of DNA coated in antimicrobial compounds. Bacteria are trapped in these NETs and are killed by the antimicrobial factors.

Nizet and colleagues found that neutrophils treated with anacardic acid produced more NETs and were more effective at killing bacteria, including MRSA. Drugs that work to clear infection by acting on the body’s immune system could serve as important supplements or alternatives to traditional antibiotics, says Nizet, especially for antibiotic-resistant superbugs like MRSA. While anacardic acid also could kill some strains of bacteria directly, it couldn’t act directly on MRSA.

There are also reasons to believe that immune-boosting drugs could be safer for patients than traditional antibiotics. Nizet explains, “Treatments that work through the immune system help preserve our microbiome, the healthy bacteria that live in our gut.” Broad-spectrum antibiotics often kill good bacteria along with bad, leading to complications such as diarrhea and opportunistic infections. Overprescription of antibiotics also has been associated with increased risks of chronic disorders from asthma to obesity.

Nizet and colleagues found that anacardic acid boosts neutrophils by interacting with receptors on the cells’ surface called spingosine-1 phosphate receptors, which set off a cascade of internal reactions in the cell called the PI3K pathway. This discovery could make it easier to design new drugs that mimic or strengthen the effect of anacardic acid on the immune system. In the near future, such immune-boosting drugs may provide a critical alternative to antibiotics in the fight against emerging antibiotic-resistant superbugs.

Melissa Bowman Melissa Bowman is a scientist and health policy communicator in Washington, D.C.