Differential synthesis of novel small protein times Salmonella virulence program

Abstract

Gene organization in operons enables concerted transcription of functionally related genes and efficient control of cellular processes. Typically, an operon is transcribed as a polycistronic mRNA that is translated into corresponding proteins. Here, we identify a bicistronic operon transcribed as two mRNAs, yet only one allows translation of both genes. We establish that the novel geneugtSforms an operon with virulence geneugtL, an activator of the master virulence regulatory system PhoP/PhoQ inSalmonella entericaserovar Typhimurium. Only the longerugtSugtLmRNA carries theugtSribosome binding site and therefore allowsugtStranslation. Inside macrophages, theugtSugtLmRNA species allowing translation of both genes is produced hours before that allowing translation solely ofugtL. The small protein UgtS controls the kinetics of PhoP phosphorylation by antagonizing UgtL activity, preventing premature activation of a critical virulence program. Moreover,S. enterica serovars that infect cold-blooded animals lackugtS. Our results establish how foreign gene control of ancestral regulators enables pathogens to time their virulence programs.