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Researchers make major progress in fighting dangerous surgical site infections

Posted by Admin | 23 Sep

In the United States alone, about 300,000 surgical patients develop infections within 30 days of surgery each year, and more than 13,000 of them die, the researchers noted. Infections lead to an estimated $10 billion in additional health care costs.

Nano dressing

A major advance in the fight against dangerous and expensive surgical site infections has been made by researchers at Oregon State University and the University of Nebraska Medical Center in nanofiber-based wound dressings that contain vitamin D. Enzyme inhibitors are added so that cells are better able to produce antimicrobial peptides.

But "because these wound dressings work by enhancing the innate immune response rather than by including traditional single-target antimicrobial compounds, they are less likely to contribute to drug resistance," said Oregon State University researcher Adrian Gombart.

Gombart, professor of biochemistry and biophysics in OSU's College of Science and principal investigator at the university's Linus Pauling Institute, and his collaborators have been exploring how vitamin D can be used to fight infection through wound dressings and sutures for years.

Vitamin D is fat-soluble and found in very few foods—including fatty fish, beef liver, cheese, and egg yolks—to facilitate the absorption of calcium in the gut and is required for bone health. Made by the body when triggered by sunlight, it is also important for cell growth, neuromuscular function, and reducing inflammation.

In this latest study, Gombart and collaborators including Oregon State University's Gitali-Ganguli Indra, Nilika Bhattacharya, Isabelle Logan, and Arup Indra tested a biologically active form of vitamin D called 1,25-dihydroxy vitamin D3, or 1,25(OH)2D3, a wound dressing -- and another compound called VID400, developed by Jingwei Xie and his team at the University of Nebraska Medical Center.

VID400 acts as a brake on the enzyme CYP24A1 that breaks down 1,25(OH)2D3.

Gombart had earlier studied the role of bioactive vitamin D in boosting the body's production of the antimicrobial peptide LL-37, which is associated with the gene CAMP present in humans and other primates. Other mammals, including mice, have a similar gene, Camp, but vitamin D doesn't trigger it to turn on LL-37 production.

To study how the vitamin D and CAMP genes work together to help prevent infection, Gombart and his research team developed a series of mice that carried the CAMP gene but not Camp. They bred mice engineered to carry human CAMP to mice knocked out of the Camp gene, resulting in mice with an antimicrobial peptide gene regulated by the biologically active form of vitamin D.

The study showed that mice with the human CAMP gene had increased resistance to intestinal infections and that staph infections on their skin could be successfully treated with the bioactive form of the vitamin.

Like previous work, the latest study used human skin tissue collected from plastic surgery patients, as well as the CAMP mouse model. It builds on earlier findings showing that VID400 prevents vitamin D degradation, which means it activates the CAMP gene better, which means better protection against infection.

nanofiber dressings containing bioactive vitamin D and VID400 help prevent surgical site infections by inducing antimicrobial peptide expression better than either compound alone," Gombart said.

understand more

Yajuan Su et al, Synergistic delivery of 1α,25-dihydroxy vitamin D3 and the CYP24A1 inhibitor VID400 by nanofiber dressing promotes induction of endogenous antimicrobial peptide LL-37, Molecular Pharmacy (2022). DOI: 10.1021/acs.molpharmaceut.1c00944