The present invention relates to
gram-negative bacterial mutants resistant to one or more
stress conditions, including, but not limited to, CO2, acid pH, and high osmolarity. The present invention also relates more particularly to
gram-negative bacterial mutants with reduced TNF-α induction having a
mutation in one or more
lipid biosynthesis genes, including, but not limited to msbB, that are rendered stress-resistant by a
mutation in the zwf
gene. The present invention provides compositions comprising one or more stress-resistant
gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. In particular, the present invention relates to methods for prophylaxis or treatment of a virally induced
disease in a subject comprising administering to said subject one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. The present invention further relates to methods for prophylaxis or treatment of a virally induced
disease in a subject comprising administering to said subject one or more stress-resistant gram-negative bacterial mutants as vectors for the delivery of one or more therapeutic molecules. The methods of the invention provide more efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.