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Microbicide Containing Engineered Bacteria May Inhibit HIV-1

Researchers from the U.S. and abroad used bacteria inherent to the human vaginal tract to develop a live, topical microbicide that may induce production of HIV-1 protein inhibitors and ultimately prevent transmission of the virus. They detail their findings in the July 2010 issue of the journal Antimicrobial Agents and Chemotherapy.

HIV-1 has killed more than 25 million people over three decades and there are currently 33 million people living with the virus worldwide. Although health officials are ultimately striving to develop an effective vaccine, topical anti-HIV-1 microbicides are a promising alternate strategy for minimizing transmission. Live microbicides are of particular interest as they utilize bacteria inherent to the human body to induce natural production of anti-HIV-1 agents.

Lactobacillus spp. are ideal candidates for live microbicide development as they are the predominant bacterial species in the female genital tract. In the study researchers engineered a human vaginal isolate of Lactobacillus jensenii capable of generating the anti-HIV-1 proteins RANTES and CIC5 RANTES which oppose the HIV-1 receptor protein, CCR5. Both RANTES variants inhibited HIV-1 infection and demonstrated significant activity against various HIV-1 genetic subtypes.

"Our results provide proof of principle for the efficient secretion of an anti-HIV-1 active CCR5 antagonist by an engineered vaginal commensal bacterium, which represents an important advancement toward realistic, safe, and low-cost prevention of sexual transmission of HIV-1," say the researchers.

(L. Vangelista, M. Secchi, X. Liu, A. Bachi, L. Jia, Q. Xu, P. Lusso. 2010. Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers.Antimicrobial Agents and Chemotherapy, 54. 7: 2994-3001.)

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