Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death

被引:85
作者
Chatterjee, I
Becker, P
Grundmeier, M
Bischoff, M
Somerville, GA
Peters, G
Sinha, B
Harraghy, N
Proctor, RA
Herrmann, M
机构
[1] Univ Saarland, Inst Med Microbiol & Hyg, Inst Infect Dis Med, D-6650 Homburg, Germany
[2] Univ Hosp Munster, Inst Med Microbiol, Munster, Germany
[3] Univ Zurich, Inst Med Microbiol, Zurich, Switzerland
[4] NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA
[5] Univ Wisconsin, Sch Med, Dept Med & Med Microbiol & Immunol, Madison, WI USA
关键词
D O I
10.1128/JB.187.13.4488-4496.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The ability of Staphylococcus aureus to adapt to various conditions of stress is the result of a complex regulatory response. Previously, it has been demonstrated that Clp homologues are important for a variety of stress conditions, and our laboratory has shown that a clpC homologue was highly expressed in the S. aureus strain DSM20231 during biofilm formation relative to expression in planktonic cells. Persistence and longterm survival are a hallmark of biofilm-associated staphylococcal infections, as cure frequently fails even in the presence of bactericidal antimicrobials. To determine the role of clpC in this context, we performed metabolic, gene expression, and long-term growth and survival analyses of DSM20231 as well as an isogenic clpC allelic-replacement mutant, a sigB mutant, and a clpC sigB double mutant. As expected, the clpC mutant showed increased sensitivity to oxidative and heat stresses. Unanticipated, however, was the reduced expression of the tricarboxylic acid (TCA) cycle gene citB (encoding aconitase), resulting in the loss of aconitase activity and preventing the catabolization of acetate during the stationary phase. clpC inactivation abolished post-stationary-phase recovery but also resulted in significantly enhanced stationary-phase survival compared to that of the wild-type strain. These data demonstrate the critical role of the ClpC ATPase in regulating the TCA cycle and implicate ClpC as being important for recovery from the stationary phase and also for entering the death phase. Understanding the stationary- and post-stationary-phase recovery in S. aureus may have important clinical implications, as little is known about the mechanisms of long-term persistence of chronic S. aureus infections associated with formation of biofilms.
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页码:4488 / 4496
页数:9
相关论文
共 50 条
[1]   A mitochondrial-like aconitase in the bacterium Bacteroides fragilis:: Implications for the evolution of the mitochondrial Krebs cycle [J].
Baughn, AD ;
Malamy, MH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (07) :4662-4667
[2]   Oxidative stress induced by ciprofloxacin in Staphylococcus aureus [J].
Becerra, MC ;
Albesa, I .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 297 (04) :1003-1007
[3]   Detection of differential gene expression in biofilm-forming versus planktonic populations of Staphylococcus aureus using micro-representational-difference analysis [J].
Becker, P ;
Hufnagle, W ;
Peters, G ;
Herrmann, M .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2001, 67 (07) :2958-2965
[4]   Teicoplanin stress-selected mutations increasing σB activity in Staphylococcus aureus [J].
Bischoff, M ;
Berger-Bächi, B .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (06) :1714-1720
[5]  
Bruckner R, 1997, FEMS MICROBIOL LETT, V151, P1
[6]  
Chan PF, 1998, J BACTERIOL, V180, P6082
[7]   Comparative genomics reveal novel heat shock regulatory mechanisms in Staphylococcus aureus and other Gram-positive bacteria [J].
Chastanet, A ;
Fert, J ;
Msadek, T .
MOLECULAR MICROBIOLOGY, 2003, 47 (04) :1061-1073
[8]   A null mutation in the Bacillus subtilis aconitase gene causes a block in Spo0A-phosphate-dependent gene expression [J].
Craig, JE ;
Ford, MJ ;
Blaydon, DC ;
Sonenshein, AL .
JOURNAL OF BACTERIOLOGY, 1997, 179 (23) :7351-7359
[9]   The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation [J].
Cramton, SE ;
Gerke, C ;
Schnell, NF ;
Nichols, WW ;
Götz, F .
INFECTION AND IMMUNITY, 1999, 67 (10) :5427-5433
[10]   CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in Gram-positive bacteria [J].
Derré, I ;
Rapoport, G ;
Msadek, T .
MOLECULAR MICROBIOLOGY, 1999, 31 (01) :117-131