Toothpicks, Serendipity and the Emergence of the <i>Escherichia coli</i> DnaK (Hsp70) and GroEL (Hsp60) Chaperone Machines

Georgopoulos, Costa

doi:10.1534/genetics.104.68262

Cited by 56 publications

(43 citation statements)

References 67 publications

(69 reference statements)

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“…DnaK, also known as heat shock protein 70, has long been recognized as a chaperone protein, in both prokaryotic and eukaryotic systems, aiding in the proper folding of proteins during biosynthesis and unfolding misfolded proteins when necessary (22,59). In F. tularensis, DnaK expression increases in response to heat and hydrogen peroxide (13); the DnaK molecular chaperone system of F. tularensis, first cloned in 1995, cross-reacts with polyclonal antisera raised against E. coli DnaK (61).…”

Section: Following Recovery From Sublethal Infection Boosting With Hmentioning

confidence: 99%

Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy

Savitt

Mena-Taboada

Monsalve

et al. 2009

Clin Vaccine Immunol

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Francisella tularensis is the causative agent of tularemia and a potential agent of biowarfare. As an easily transmissible infectious agent, rapid detection and treatment are necessary to provide a positive clinical outcome. As an agent of biowarfare, there is an additional need to prevent infection. We made monoclonal antibodies to the F. tularensis subsp. holarctica live vaccine strain (F. tularensis LVS) by infecting mice with a sublethal dose of bacteria and, following recovery, by boosting the mice with sonicated organisms. The response to the initial and primary infection was restricted to immunoglobulin M antibody directed solely against lipopolysaccharide (LPS). After boosting with sonicated organisms, the specificity repertoire broadened against protein antigens, including DnaK, LpnA, FopA, bacterioferritin, the 50S ribosomal protein L7/L12, and metabolic enzymes. These monoclonal antibodies detect F. tularensis LVS by routine immunoassays, including enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence. The ability of the antibodies to protect mice from intradermal infection, both prophylactically and therapeutically, was examined. An antibody to LPS which provides complete protection from infection with F. tularensis LVS and partial protection from infection with F. tularensis subsp. tularensis strain SchuS4 was identified. There was no bacteremia and reduced organ burden within the first 24 h when mice were protected from F. tularensis LVS infection with the anti-LPS antibody. No antibody that provided complete protection when administered therapeutically was identified; however, passive transfer of antibodies against LPS, FopA, and LpnA resulted in 40 to 50% survival of mice infected with F. tularensis LVS.

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Section: Following Recovery From Sublethal Infection Boosting With Hmentioning

confidence: 99%

Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy

Savitt

Mena-Taboada

Monsalve

et al. 2009

Clin Vaccine Immunol

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“…This consists of rapid upregulation of a set of proteins, the heat-shock proteins (Hsps), most of which reduce the intracellular level of unfolded and aggregated proteins. The major Hsps fall into two categories: molecular chaperones which promote correct protein folding (Hartl et al, 1992;Hartl, 1996;Lund, 2001;Georgopoulos, 2006) and ATP-dependent proteases that degrade unfolded polypeptides (Neuwald et al, 1999;Suzuki et al, 1997;Dougan et al, 2002). Both groups also have roles in protein quality control within the cell under normal conditions, and their importance is shown by their high conservation.…”

Section: Introductionmentioning

confidence: 99%

The hrcA and hspR regulons of Campylobacter jejuni

2010

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The human pathogen Campylobacter jejuni has a classic heat shock response, showing induction of chaperones and proteases plus several unidentified proteins in response to a small increase in growth temperature. The genome contains two homologues to known heat shock response regulators, HrcA and HspR. Previous work has shown that HspR controls several heat-shock genes, but the hrcA regulon has not been defined. We have constructed single and double deletions of C. jejuni hrcA and hspR and analysed gene expression using microarrays. Only a small number of genes are controlled by these two regulators, and the two regulons overlap. Strains mutated in hspR, but not those mutated in hrcA, showed enhanced thermotolerance. Some genes previously identified as being downregulated in a strain lacking hspR showed no change in expression in our experiments.

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“…7). GroEL/ES and DnaK/DnaJ are primary chaperones dedicated to protection against stress-induced protein aggregation (53). GroEL has been shown to protect bovine catalase against thermal stress (54).…”

mentioning

confidence: 99%

Synergistic Roles of Helicobacter pylori Methionine Sulfoxide Reductase and GroEL in Repairing Oxidant-damaged Catalase

Mahawar¹,

Tran

Sharp

et al. 2011

Journal of Biological Chemistry

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Hypochlorous acid (HOCl) produced via the enzyme myeloperoxidase is a major antibacterial oxidant produced by neutrophils, and Met residues are considered primary amino acid targets of HOCl damage via conversion to Met sulfoxide. Met sulfoxide can be repaired back to Met by methionine sulfoxide reductase (Msr). Catalase is an important antioxidant enzyme; we show it constitutes 4 -5% of the total Helicobacter pylori protein levels. msr and katA strains were about 14-and 4-fold, respectively, more susceptible than the parent to killing by the neutrophil cell line HL-60 cells. Catalase activity of an msr strain was much more reduced by HOCl exposure than for the parental strain. Treatment of pure catalase with HOCl caused oxidation of specific MS-identified Met residues, as well as structural changes and activity loss depending on the oxidant dose. Treatment of catalase with HOCl at a level to limit structural perturbation (at a catalase/HOCl molar ratio of 1:60) resulted in oxidation of six identified Met residues. Msr repaired these residues in an in vitro reconstituted system, but no enzyme activity could be recovered. However, addition of GroEL to the Msr repair mixture significantly enhanced catalase activity recovery. Neutrophils produce large amounts of HOCl at inflammation sites, and bacterial catalase may be a prime target of the host inflammatory response; at high concentrations of HOCl (1:100), we observed loss of catalase secondary structure, oligomerization, and carbonylation. The same HOCl-sensitive Met residue oxidation targets in catalase were detected using chloramine-T as a milder oxidant.

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Toothpicks, Serendipity and the Emergence of the Escherichia coli DnaK (Hsp70) and GroEL (Hsp60) Chaperone Machines

Cited by 56 publications

References 67 publications

Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy

Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy

The hrcA and hspR regulons of Campylobacter jejuni

Synergistic Roles of Helicobacter pylori Methionine Sulfoxide Reductase and GroEL in Repairing Oxidant-damaged Catalase

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