Summary Naturally invasive bacteria have been successfully used for mucosal delivery of DNA vaccines against bacterial, viral and tumour antigens. Recently, an alternative delivery system based on a genetically modified mutant of the non-pathogenic commensal bacterium Escherichia coli, was developed and successfully used to deliver therapeutic genes and immunogenic proteins to epithelial cells in vivo. In this work, we used these recombinant invasive bacteria to deliver DNA vaccines against two Mycobacterium tuberculosis proteins (FbpA, and HtpX) following intranasal administration. Both DNA vaccines were able to induce an antigen-specific T-cell response. Moreover, mice immunized with the recombinant bacteria carrying the DNA vaccine encoding HtpX, were significatively protected from challenge with M. tuberculosis.