Skip to main content

Peptide quells “genomic storm”

Oct. 28, 2014, 8:00 AM

by T.J. Utset

(iStock)

Vanderbilt University researchers have found a way to block the signaling pathways that lead to lethal shock, a deadly complication of infections caused by Gram-negative bacteria that produce the endotoxin lipopolysaccharide (LPS), a potent virulence factor.

In the journal PLOS ONE, Antonio DiGiandomenico, Ph.D., Jacek Hawiger, M.D., Ph.D., and colleagues report that a cell-penetrating peptide they developed, cSN50.1, dramatically increased survival in mice exposed to high doses of LPS.

When LPS binds to its sensors on immune and vascular cells, it triggers mobilization of stress-responsive transcription factors (SRTFs) to the nucleus. In this signaling cascade, specialized proteins called importins/karyopherins ferry SRTFs into the cell nucleus where they reprogram gene expression. The ensuing “genomic storm” ramps up production of inflammatory molecules that induce fever and blood vessel injury. When left unchecked, this ultimately leads to multiple organ failure and death.

The cSN50.1 peptide targets importins, thereby reducing nuclear transport of SRTFs. The researchers concluded that controlling nuclear import may aid antibiotics in treating Gram-negative bacterial infections.

This work was supported by National Institutes of Health grants HL087531, HL069452, HL069765, DK090146 and HL087531, the Vanderbilt Immunotherapy Program, and was dedicated to the late Dr. Robert D. Collins, a longtime mentor, colleague, and friend to the authors.

Send suggestions for articles to highlight in Aliquots and any other feedback about the column to aliquots@vanderbilt.edu

Recent Stories from VUMC News and Communications Publications

Betsy Williams has firsthand advice for parents on the fence about whether their adolescent children should be vaccinated for the common human papilloma virus (HPV), which can lead to six types of cancer.  Don’t hesitate. Do it.

Momentum

Betsy Williams has firsthand advice for parents on the fence about whether their adolescent children should be vaccinated for the common human papilloma virus (HPV), which can lead to six types of cancer. Don’t hesitate. Do it.

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

Vanderbilt Medicine

Keeping pace: Nashville, once a mid-size city with a Southern small-town feel, is experiencing explosive growth.

VUMC campus

VUMC campus

Vanderbilt University School of Medicine entrance

Vanderbilt University School of Medicine entrance

more