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HIV/AIDS Drug Development: Genetically engineered live bacteria block HIV fusion and entry

AIDSWEEKLY Plus; Monday, November 7, 2005
Staff Medical Writers


NewsRx -- Genetically engineered live bacteria block HIV fusion and entry.

"Most HIV transmission occurs on the mucosal surfaces of the gastrointestinal and cervicovaginal tracts, both of which are normally coated by a biofilm of nonpathogenic commensal bacteria. We propose to genetically engineer such naturally occurring bacteria to protect against HIV infection by secreting antiviral peptides," scientists in the United States report.

"Here we describe the development and characterization of Nissle 1917, a highly colonizing probiotic strain of Escherichia coli, secreting HIV-gp41-hemolysin A hybrid peptides that block HIV fusion and entry into target cells.

"By using an appropriate combination of cis- and transacting secretory and regulatory signals, micromolar secretion levels of the anti-HIV peptides were achieved," wrote S. Rao and colleagues at the U.S. National Institutes of Health.

"The genetically engineered Nissle 1917 were capable of colonizing mice for periods of weeks to months, predominantly in the colon and cecum, with lower concentrations of bacteria present in the rectum, vagina, and small intestine.

"Histological and immunocytochemical examination of the colon revealed bacterial growth and peptide secretion throughout the luminal mucosa and in association with epithelial surfaces," investigators said.

The authors concluded, "The use of genetically engineered live microbes as anti-HIV microbicides has important potential advantages in economy, efficacy, and durability."

Rao and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):11993-8.

For additional information, contact D.H. Hamer, NCI, Biochemistry Laboratory, NIH, 9000 Rockville Pike, Bldg 37, Room 6002, Bethesda, MD 20892, USA.

The publisher's contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Academy Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA.

Keywords: Bethesda, Maryland, United States, HIV/AIDS, Microbicide, Genetically Engineered Bacteria, HIV Fusion Inhibitor, Biofilm, Antiviral Peptides, Secretory Signals, Regulatory Signals, Nissle 1917.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Rao S, Hu S, McHugh L, et al., "Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide"Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):11993-8.

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