Listeria monocytogenes regulates flagellar motility gene expression through MogR, a transcriptional repressor required for virulence.
Previous studies have shown that Listeria monocytogenes flagellar motility genes, including flaA, encoding flagellin, are transcriptionally down-regulated at 37 degrees C. For some L. monocytogenes strains, temperature-dependent motility gene expression is less stringent. By using flaA-lacZ transcriptional fusions, we identified regions upstream of the -35/-10 promoter elements that are necessary for temperature-dependent expression of flaA in L. monocytogenes strain EGDe. Whereas the sequence of the flaA promoter region was identical in L. monocytogenes strain 10403S, transcriptional activity was only partially down-regulated at 37 degrees C in 10403S. This finding suggested that a transacting regulatory protein with differential expression or activity in EGDe might be involved in temperature-dependent transcription of flaA. Indeed, a protein factor capable of specifically binding to the flaA promoter region was identified in cytoplasmic extracts of EGDe by using affinity purification and MS. Deletion of the factor-encoding gene (lmo0674) resulted in loss of temperature-dependent flaA expression and an increase in flaA promoter activity. Expression of other motility genes was also deregulated in the lmo0674 deletion. We have designated lmo0674 as mogR, indicating its role as a motility gene repressor. In tissue culture models, MogR repression of flaA during intracellular infection was independent of temperature and a deletion of mogR reduced the capacity for cell-to-cell spread. During in vivo infection, a deletion of mogR resulted in a 250-fold decrease in virulence. These studies indicate that regulation of flagellar motility gene expression and/or other genes controlled by MogR is required for full virulence of L. monocytogenes.
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Angelika
A
Gründling
Laura S
LS
Burrack
H G Archie
HG
Bouwer
Darren E
DE
Higgins
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005407:Flagella / Q000502:physiology*; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009068:Movement; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D013696:Temperature; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D005408:Flagellin; C067138:flaA protein, bacteria