abstract |
The present invention provides genetically modified microorganisms (eg bacteria or yeast) with improved mucin-binding and/or cell-adhesive properties. For example, the present invention provides bacteria that exhibit increased in vitro binding to Caco-2 cells and increased in vitro binding to mucins. Such microorganisms (eg bacteria) can be used, for example, for delivery of bioactive polypeptides to the gastrointestinal tract of mammalian subjects. Microbial modification in the manner described above allows control of the gastrointestinal retention and transit time of microbes (eg, bacteria). Exemplary microorganisms (eg, lactic acid bacteria, such as Lactococcus lactis) contain cell-adherent polypeptides such as CmbA and mucin-binding polypeptides such as trefoil factor (TFF), such as human TFF3 contains an exogenous nucleic acid encoding a fusion protein that The present invention further provides methods for making and using the described microorganisms (eg, bacteria). |