DMSA PROMOTERS AND DERIVATIVES THEREOF USED FOR CONTROLLED EXPRESSION OF FOREIGN GENES

摘要

A novel bacterial vector capable of expressing foreign proteins in vivo is disclosed herein. The expression is specifically controlled by an anaerobically inducible FNR promoter, dmsA or its derivatives, operatively linked to a DNA sequence encoding the protein of interest. The dmsA promoter allows for in vivo expression of foreign proteins, such as vaccine antigens, in live attenuated vaccine strains. Two derivatives of dmsA were engineered to enhance the expression under anaerobic growth conditions by otpimizing the FNR binding sequence. The protein expression driven by these promoters was tightly controlled by anaerobiosis and to a lesser extent, inhibited by nitrate. The use of dmsA promoter derivatives for expression of foreign proteins in live attenuated vaccines offers a modular promoter system for expression of proteins at different levels. This allows tailoring an optimal expression system by matching the level of expression of a specific foreign gene while imposing minimal metabolic stress on the carrier strain.