Open AccessDifferential synthesis of novel small protein times Salmonella virulence program
Author(s) -
Hubert Salvail,
Jeongjoon Choi,
Eduardo A. Groisman
Publication year - 2022
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1010074
Subject(s) - operon , virulence , biology , gene , translation (biology) , salmonella enterica , transcription (linguistics) , genetics , ribosome , protein biosynthesis , messenger rna , ribosomal binding site , activator (genetics) , regulation of gene expression , mutant , rna , escherichia coli , linguistics , philosophy
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 gene ugtS forms an operon with virulence gene ugtL , an activator of the master virulence regulatory system PhoP/PhoQ in Salmonella enterica serovar Typhimurium. Only the longer ugtSugtL mRNA carries the ugtS ribosome binding site and therefore allows ugtS translation. Inside macrophages, the ugtSugtL mRNA species allowing translation of both genes is produced hours before that allowing translation solely of ugtL . 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 lack ugtS . Our results establish how foreign gene control of ancestral regulators enables pathogens to time their virulence programs.