Role of the Streptococcus agalactiae ClpP serine protease in heat-induced stress defence and growth arrest.
The main causes of microbial death after heat exposure are not well understood. Here, it is shown that the heat-shock protein ClpP plays a major role in heat-induced growth arrest in Streptococcus agalactiae. A mutant lacking the ClpP protease was more sensitive to the inhibitory effects of heat, salt and oxidative stress than the isogenic wild-type strain. During growth arrest, this mutant displayed important modifications of its total protein content, including a decreased level of essential metabolic enzymes such as the alcohol dehydrogenase. Analysis of protein carbonylation demonstrated that the ClpP protease plays a role in preventing accelerated protein oxidation. Higher levels of oxidized DnaK, a key modulator of the heat-shock regulon, were observed in the ClpP mutant and these were increased following heat shock. Accumulation of oxidized/inactivated DnaK might explain why the ClpP mutant was unable to properly synthesize DNA and proteins, and why it exhibited an aberrant cell morphology. Even though ClpP plays a minor role in the virulence of S. agalactiae in a murine infection model, the data presented here point to the importance of ClpP in oxidative stress defence in preventing heat-induced cell alterations.
Nair
Shamila
S
INSERM U411, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Poyart
Claire
C
Laboratoire Mixte Pasteur-Necker de Recherche sur les Streptocoques et Streptococcies, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.|INSERM U411, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Beretti
Jean-Luc
JL
INSERM U411, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Veiga-Fernandes
Herrique
H
INSERM U345, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Berche
Patrick
P
INSERM U411, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Trieu-Cuot
Patrick
P
Laboratoire Mixte Pasteur-Necker de Recherche sur les Streptocoques et Streptococcies, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.|INSERM U411, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D049071:Endopeptidase Clp; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000201:enzymology* / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases