Apicoplast Lipoic Acid Protein Ligase B Is Not Essential for Plasmodium falciparum

Günther, Svenja; Wallace, Lynsey J. M.; Patzewitz, Eva‐Maria; McMillan, Paul J.; Storm, Janet; Wrenger, Carsten; Bissett, Ryan; Smith, Terry; Müller, Sylke

doi:10.1371/journal.ppat.0030189

Cited by 53 publications

(100 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the PDHs of Gram-positive bacteria and all BCDHs and AoDHs are com- VOL. 74,2010 LIPOIC ACID METABOLISM IN MICROBIAL PATHOGENS 201 posed of two proteins, E1␣ and E1␤, arranged as heterotetramers (␣ 2 ␤ 2 ). In both cases, the E1 multimers contain two thiamine pyrophosphate (TPP) cofactors that are thought to communicate through a "proton wire" and act in a reciprocal manner during catalysis (51).…”

Section: Structure Of Lipoylated Complexesmentioning

confidence: 99%

“…VOL. 74,2010 LIPOIC ACID METABOLISM IN MICROBIAL PATHOGENS 203 and excess pyruvate and is suppressed during fermentative growth (31). In eukaryotes, in addition to allosteric regulation of the PDH by accumulation of product, activity is also controlled through phosphorylation of the E1 subunit (122).…”

Section: Lipoylated Complexesmentioning

confidence: 99%

“…The BCDH is anticipated to generate the primers for branched-chain fatty acid synthesis in this species, as it does in other bacterial species such as Listeria monocytogenes (described in "GramPositive Bacteria" below), in which branched-chain fatty acids VOL. 74,2010 LIPOIC ACID METABOLISM IN MICROBIAL PATHOGENS 209 predominate. In contrast, BCFAs are found in only trace amounts in P. aeruginosa (145,146), and in this species, the role of the BCDH may be to support the full catabolism of valine, isoleucine, and leucine to TCA cycle intermediates, such as acetyl-CoA and succinyl-CoA.…”

Section: Gram-negative Bacteriamentioning

confidence: 99%

“…The production of mature RPM1 RNA requires the endonuclease activity of VOL. 74,2010 LIPOIC ACID METABOLISM IN MICROBIAL PATHOGENS 215 RNase P, providing a possible feedback mechanism regulating the processing of mitochondrial RNAs (Fig. 4).…”

Section: Metabolic Regulationmentioning

confidence: 99%

See 3 more Smart Citations

Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

160

186

View full text Add to dashboard Cite

SUMMARY Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.

show abstract

Section: Structure Of Lipoylated Complexesmentioning

confidence: 99%

Section: Lipoylated Complexesmentioning

confidence: 99%

Section: Gram-negative Bacteriamentioning

confidence: 99%

Section: Metabolic Regulationmentioning

confidence: 99%

See 2 more Smart Citations

Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

160

186

View full text Add to dashboard Cite

show abstract

“…In the last decade, techniques for genetic manipulation of P. falciparum have become available (59,60). Molecular tools for gene disruption were developed and led to the identification of several parasite-derived proteins along with the elucidation of their function and mechanism (60)(61)(62). Research was not only based on identification and characterization of enzymes involved in transportation processes and metabolic functions but also on secreted proteins such as the PfEMP1 protein (parasite-derived erythrocyte membrane protein) or the knobassociated histidine-rich protein (KAHRP), which participate in the ''knob'' formation and are believed to be involved in REVIEW ARTICLE cytoadherance (63).…”

Section: Employing Aptamers On Parasite Infectionmentioning

confidence: 99%

Disease‐specific biomarker discovery by aptamers

Ulrich

Wrenger

2009

Cytometry Pt A

Self Cite

View full text Add to dashboard Cite

RNA and DNA aptamers developed by an in vitro selection process, Systematic Evolution of Ligands by EXponential enrichment (SELEX), comprise a novel class of highaffinity and specific capture agents, which can be easily modified for cytometry and in vivo applications. A novel application of this technique (Cell SELEX) explores the expression of cell surface epitopes that differ between two given cell types or between healthy and diseased cells. Using whole cells as targets, aptamer libraries can be identified that bind to biomarkers expressed by target cells and not by any other cells. Aptamers have been developed that specifically interact with cell surface epitopes of trypanosomes or distinguish between the differences in molecular signature of somatic and cancer cells. Aside from its use for target cell identification by image and flow cytometry and laser-scanning microscopy, aptamers can be used for ligand-mediated purification and identification of their binding proteins in target cell membranes. In this review, we discuss an approach for the development of aptamers targeting parasitederived surface proteins of Trypanosoma and Plasmodium. ' 2009 International Society for Advancement of CytometryKey terms aptamers; Plasmodium falciparum; deconvolution SELEX; cell and target protein identification; fluorescence-labeled aptamers for clinical and cytomics application THE SELEX TECHNOLOGYThe SELEX technique (Systematic Evolution of Ligands by EXponential enrichment) initially developed by the laboratories of Larry Gold (1) and Jack Szostak (2) uses iterative in vitro selection of combinatorial RNA or DNA pools against a target molecule for the identification of high-affinity oligonucleotide ligands, known as aptamers. This methodology has been extensively used to isolate aptamers for a wide variety of peptides and proteins of therapeutic importance, including growth and coagulation factors (3). This novel class of oligonucleotide-based ligands recognizes their targets with binding specificities and affinities comparable to those of monoclonal antibodies. Moreover, aptamers are able to distinguish between protein isoforms and different conformational forms of the same protein (4,5). In most cases, aptamer binding to its target protein inhibits its biological activity, either resulting from aptamer interference with the catalytic site of an enzyme or with sites involved in ligandreceptor recognition. However, it is also possible that aptamer-target protein binding induces allosteric effects, such as changes in conformational states resulting in loss of biological activity of the target protein.Aptamers can be identified by in vitro selection against almost any target, including toxins and antigens which do not induce immune responses in host animals for antibody production. As a result, this novel class of ligands is highly promising for the development of therapeutics and biotechnological tools. The potential utility of aptamers for in vivo applications and as therapeutic agents is considerably enhanced ...

show abstract