Lactobacillus bacteria are potential delivery vehicles for biopharmaceutical molecules because they are well-recognized as safe microorganisms that naturally inhabit the human body. The goal of this study is to employ these lactobacilli to combat human immunodeficiency virus (HIV-1) infection and transmission. By using a chromosomal integration method, we engineered the Lactobacillus helveticus R0052 strain to display human CD4, the HIV-1 receptor, on the cell surface. Since human CD4 can bind to any infectious HIV-1 particles, the engineered lactobacilli can potentially capture HIV-1 of different sub-types and prevent infection. Our data demonstrate that the CD4-carrying bacteria are able to adsorb HIV-1 particles and reduce infection significantly in vitro, and also block intrarectal HIV-1 infection in a humanized mouse model in preliminary tests in vivo. Our results support the potential of this approach to decrease the efficiency of HIV-1 sexual transmission. [ABSTRACT FROM AUTHOR]