TY - JOUR
T1 - Clp chaperones and proteases are central in stress survival, virulence and antibiotic resistance of Staphylococcus aureus
AU - Frees, Dorte
AU - Gerth, Ulf
AU - Ingmer, Hanne
N1 - Copyright © 2013 Elsevier GmbH. All rights reserved.
PY - 2014/3
Y1 - 2014/3
N2 - Intracellular proteolysis carried out by energy-dependent proteases is one of the most conserved biological processes. In all cells proteolysis maintains and shapes the cellular proteome by ridding the cell of damaged proteins and by regulating abundance of functional proteins such as regulatory proteins. The ATP-dependent ClpP protease is highly conserved among eubacteria and in the chloroplasts and mitochondria of eukaryotic cells. In the serious human pathogen, Staphylococcus aureus inactivation of clpP rendered the bacterium avirulent emphasizing the central role of proteolysis in virulence. The contribution of the Clp proteins to virulence is likely to occur at multiple levels. First of all, both Clp ATPases and the Clp protease are central players in stress responses required to cope with the adverse conditions met in the host. The ClpP protease has a dual role herein, as it both eliminates stress-damaged proteins as well as ensures the timely degradation of major stress regulators such as Spx, LexA and CtsR. Additionally, as we will summarize in this review, Clp proteases and Clp chaperones impact on such central processes as virulence gene expression, cell wall metabolism, survival in stationary phase, and cell division. These observations together with recent findings that Clp proteins contribute to adaptation to antibiotics highlights the importance of this interesting proteolytic machinery both for understanding pathogenicity of the organism and for treating staphylococcal infections.
AB - Intracellular proteolysis carried out by energy-dependent proteases is one of the most conserved biological processes. In all cells proteolysis maintains and shapes the cellular proteome by ridding the cell of damaged proteins and by regulating abundance of functional proteins such as regulatory proteins. The ATP-dependent ClpP protease is highly conserved among eubacteria and in the chloroplasts and mitochondria of eukaryotic cells. In the serious human pathogen, Staphylococcus aureus inactivation of clpP rendered the bacterium avirulent emphasizing the central role of proteolysis in virulence. The contribution of the Clp proteins to virulence is likely to occur at multiple levels. First of all, both Clp ATPases and the Clp protease are central players in stress responses required to cope with the adverse conditions met in the host. The ClpP protease has a dual role herein, as it both eliminates stress-damaged proteins as well as ensures the timely degradation of major stress regulators such as Spx, LexA and CtsR. Additionally, as we will summarize in this review, Clp proteases and Clp chaperones impact on such central processes as virulence gene expression, cell wall metabolism, survival in stationary phase, and cell division. These observations together with recent findings that Clp proteins contribute to adaptation to antibiotics highlights the importance of this interesting proteolytic machinery both for understanding pathogenicity of the organism and for treating staphylococcal infections.
U2 - 10.1016/j.ijmm.2013.11.009
DO - 10.1016/j.ijmm.2013.11.009
M3 - Journal article
C2 - 24457183
SN - 1438-4221
VL - 304
SP - 142
EP - 149
JO - International Journal of Medical Microbiology
JF - International Journal of Medical Microbiology
IS - 2
ER -