Cholesterol-lowering Drug May Also Fight Infectious Disease

A new study from researchers at Duke University may shed light on what makes individuals susceptible to infectious diseases such as typhoid fever, chlamydia, and malaria, and how cholesterol levels may impact susceptibility.

Typhoid fever, caused by Salmonella Typhi bacteria, is responsible for 5,700 cases in the United States each year, according to the Centers for Disease Control and Prevention (CDC). Outside of the United States, the World Health Organization (WHO) says that typhoid fever causes an estimated 21 million cases and 222,000 related deaths worldwide each year, and children make up most of those deaths.

Salmonella Typhi bacteria spread through contaminated food and water, causing illness marked by prolonged fever, headache, nausea, loss of appetite, and constipation or diarrhea. Severe cases of typhoid fever can lead to complications or death. Two vaccines are available to prevent and control outbreaks, though neither is recommended for children under the age of 2.

Following recent flooding in parts of India, health officials have been on the alert for a spike in water-borne diseases there, including typhoid fever. The news brings added importance to a recent study by Duke University researchers, published in the journal Proceedings of the National Academy of Sciences. The authors noted that when it comes to infectious diseases such as typhoid, the risk and severity of infection depends on a combination of pathogen virulence and host susceptibility. They studied how genetic variation may affect human disease susceptibility to pathogens such as S. Typhi. The researchers focused on the role of cholesterol, finding that a gene called VAC14 regulates bacterial invasion, and that decreased expression of the gene led to increased plasma membrane cholesterol. They observed that Salmonella use the elevated cholesterol in cell membranes to bind to and invade cells, and that cells with higher cholesterol saw increased Salmonella invasion.

The researchers used zebrafish, which have been used in previous studies on disease transmission and pathogenesis, to study how reducing cholesterol levels impacted infection. They found that zebrafish that were given the cholesterol-lowering drug ezetimibe showed increased clearance of S. Typhi, suggesting that statins administered to lower the risk of a heart attack may also help lower the risk of certain diseases.

“Our study is primarily focused on human genetic variation affecting susceptibility to Salmonella invasion and typhoid fever, though we do demonstrate that a cholesterol-lowering drug is protective in a zebrafish model of infection,” explained senior author Dennis C. Ko, MD, PhD, to Contagion ^®.

While the study may indicate that statins given to reduce cholesterol levels may one day play an additional role in infection prevention, the authors note the need for further research. “This is just the first step,” said Dr. Ko in a recent press release. “We need to try this approach in different model organisms, such as mice, and likely with different pathogens, before we can consider taking this into the clinic. What’s so exciting is that our study provides a blueprint for combining different techniques for understanding why some people are more susceptible to disease than others, and what can be done about it.”