Identification of the agr locus of Listeria monocytogenes: role in bacterial virulence.
Listeria monocytogenes is a gram-positive facultative intracellular food-borne pathogen that can cause severe infections in humans and animals. We have recently adapted signature-tagged transposon mutagenesis (STM) to identify genes involved in the virulence of L. monocytogenes. A new round of STM allowed us to identify a new locus encoding a protein homologous to AgrA, the well-studied response regulator of Staphylococcus aureus and part of a two-component system involved in bacterial virulence. The production of several secreted proteins was modified in the agrA mutant of L. monocytogenes grown in broth, indicating that the agr locus influenced protein secretion. Inactivation of agrA did not affect the ability of the pathogen to invade and multiply in cells in vitro. However, the virulence of the agrA mutant was attenuated in the mouse (a 10-fold increase in the 50% lethal dose by the intravenous route), demonstrating for the first time a role for the agr locus in the virulence of L. monocytogenes.
Autret
Nicolas
N
INSERM U-570, CHU Necker-Enfants Malades, 75730 Paris Cedex 15, France.
Raynaud
Catherine
C
Dubail
Iharilalao
I
Berche
Patrick
P
Charbit
Alain
A
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D018938:Caco-2 Cells; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D000071677:Histidine Kinase; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011494:Protein Kinases / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015534:Trans-Activators; D011494:Protein Kinases; D000071677:Histidine Kinase