The MogR Transcriptional Repressor Regulates Nonhierarchal Expression of Flagellar Motility Genes and Virulence in Listeria monocytogenes

Open Access
Publisher Website
Google Scholar
Abstract
Flagella are surface structures critical for motility and virulence of many bacterial species. In Listeria monocytogenes, MogR tightly represses expression of flagellin (FlaA) during extracellular growth at 37 °C and during intracellular infection. MogR is also required for full virulence in a murine model of infection. Using in vitro and in vivo infection models, we determined that the severe virulence defect of MogR-negative bacteria is due to overexpression of FlaA. Specifically, overproduction of FlaA in MogR-negative bacteria caused pleiotropic defects in bacterial division (chaining phenotype), intracellular spread, and virulence in mice. DNA binding and microarray analyses revealed that MogR represses transcription of all known flagellar motility genes by binding directly to a minimum of two TTTT-N5-AAAA recognition sites positioned within promoter regions such that RNA polymerase binding is occluded. Analysis of MogR protein levels demonstrated that modulation of MogR repression activity confers the temperature-specificity to flagellar motility gene expression. Epistasis analysis revealed that MogR repression of transcription is antagonized in a temperature-dependent manner by the DegU response regulator and that DegU further regulates FlaA levels through a posttranscriptional mechanism. These studies provide the first known example to our knowledge of a transcriptional repressor functioning as a master regulator controlling nonhierarchal expression of flagellar motility genes. Bacteria move in liquid environments using hair-like structures on their surface called flagella. Production of flagella requires more than 40 genes and a significant amount of energy. Indeed, a single flagella filament is composed of approximately 20,000 flagellin subunits. In the environment, bacteria use flagella to swim toward nutrients. Flagella are also important for disease-causing bacteria (pathogens) to initiate infections. However, once inside a person, flagellin is a potent stimulator of the human immune system. Consequently, many bacteria decrease production of flagella shortly after infection. Listeria monocytogenes is a pathogen that grows inside of human cells. In this study, the authors show that L. monocytogenes produce a unique protein (MogR) that downregulates production of all of the genes required to produce flagella. This mode of flagella regulation has not been previously observed in bacteria. The authors demonstrate that in the absence of MogR, L. monocytogenes overproduce flagellin. Misregulation of flagellin production results in bacteria that are no longer able to efficiently enter host cells and are less pathogenic. Thus, the authors demonstrate that MogR-dependent repression of flagellin production is essential for L. monocytogenes to grow inside of host cells.