Live microbial microbicides

Abstract

The present invention relates, e.g., to a commensal bacterium which can colonize the genitourinary and/or gastrointestinal mucosa, and which, under suitable conditions, secretes a heterologous antimicrobial polypeptide, wherein the secreted antimicrobial polypeptide is effective to inhibit infectivity by, or a pathogenic activity of, a pathogen. In a most preferred embodiment, the antimicrobial polypeptide inhibits HIV infection (e.g., fusion) and/or pathogenesis. Also described are preventive or therapeutic compositions comprising the commensal bacteria, and methods to inhibit infectivity and/or pathogenesis, using the bacteria.

1 . A commensal bacterium which can colonize genitourinary and/or gastrointestinal mucosa, and which, under suitable conditions, secretes a recombinant, antimicrobial polypeptide in an amount effective to inhibit infectivity by, and/or a pathogenic activity of, a pathogen, wherein the bacterium is  Lactobacillus  and the recombinant, antimicrobial polypeptide is cyanovirin. 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The commensal bacterium of  claim 1 , wherein the antimicrobial polypeptide is fused in phase to a carboxyterminal secretion signal of the hemolysin A gene. 
     
     
         6 - 13 . (canceled) 
     
     
         14 . The commensal bacterium of  claim 1 , wherein the pathogen is HIV. 
     
     
         15 - 18 . (canceled) 
     
     
         19 . The commensal bacterium of  claim 1 , wherein the secretion is mediated by a secretion signal that is a secretion-effective C-terminal fragment of HlyA. 
     
     
         20 . The commensal bacterium of  claim 1 , wherein the expression is under the control of an expression control sequence that comprises a constitutive promoter. 
     
     
         21 . The commensal bacterium of  claim 20 , wherein the expression control sequence comprises a promoter from the  E. coli  lac operon and a translational control sequence from bacteriophage T7. 
     
     
         22 . The commensal bacterium of  claim 1 , which comprises, stably integrated into its chromosome, sequences encoding an antimicrobial polypeptide fused in frame to a secretory signal, operably linked to an expression control sequence. 
     
     
         23 . A pharmaceutical composition, comprising an effective amount of a commensal bacterium of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . A method for inhibiting HIV infectivity and/or pathogenicity in a subject in need of such treatment, comprising administering to the subject an effective amount of a commensal bacterium of  claim 14 , under conditions in which the anti-microbial polypeptide is secreted in an amount effective to inhibit HIV infectivity and/or pathogenicity. 
     
     
         27 - 35 . (canceled)