Identification of a ClpC ATPase required for stress tolerance and in vivo survival of Listeria monocytogenes.
We identified a new chromosomal locus involved in the virulence of the facultative intracellular pathogen Listeria monocytogenes. This locus displays the same genetic organization as that of the clpC/mecB locus of Bacillus subtilis. It contains a thermoregulated operon of four genes, whose transcription is upregulated at 42 degrees C. The last gene of this operon is clpC, which encodes a protein of 826 amino acid residues, identified as a ClpC ATPase, sharing a strong peptide sequence identity (78%) with ClpC/MecB of B. subtilis. Tn917 insertions inactivating the entire operon, or only clpC, gave mutants highly susceptible to stress, including iron limitation, elevated temperatures and high osmolarity. The virulence of these mutants was severely impaired in the mouse. A clpC insertional mutant was also restricted in its capacity to grow in bone-marrow-derived macrophages. These results demonstrate that the ClpC ATPase of L. monocytogenes is a general stress protein involved in intracellular growth and in vivo survival of this pathogen in host tissues.
Rouquette
C
C
INSERM U 411, Faculté de Médecine Necker, Paris, France.
Ripio
M T
MT
Pellegrini
E
E
Bolla
J M
JM
Tascon
R I
RI
Vázquez-Boland
J A
JA
Berche
P
P
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010641:Phenotype; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D006360:Heat-Shock Proteins; D007501:Iron; D000251:Adenosine Triphosphatases