Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49

Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

doi:10.1016/j.pep.2013.07.002

Cited by 21 publications

(24 citation statements)

References 56 publications

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“…11 Following purification, ADI activity was assayed by measuring the rate of ammonia produced by the conversion of L-Arg to L-citrulline as described using Ammonia Assay Kit (Sigma, AA0100). 11 Here, L-glutamate dehydrogenase catalyzes the reaction of ammonia, a-ketoglutaric acid (KGA), and reduced nicotinamide adenine dinucleotide phosphate (NADPH) to L-glutamate and oxidized nicotinamide adenine dinucleotide phosphate (NADP C ). The decrease in absorbance at 340 nm due to the oxidation of NADPH was measured.…”

Section: Methodsmentioning

confidence: 99%

Arginine deprivation by arginine deiminase ofStreptococcus pyogenescontrols primary glioblastoma growthin vitroandin vivo

Fiedler

Strauss

Hering

et al. 2015

Cancer Biology & Therapy

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Arginine auxotrophy constitutes a weak point of several tumors, among them glioblastoma multiforme (GBM). Hence, those tumors are supposed to be sensitive for arginine-depleting substances, such as arginine deiminase (ADI). Here we elucidated the sensitivity of patient-individual GBM cell lines toward Streptococcus pyogenes-derived ADI. To improve therapy, ADI was combined with currently established and pre-clinical cytostatic drugs. Additionally, effectiveness of local ADI therapy was determined in xenopatients. Half of the GBM cell lines tested responded well toward ADI monotherapy. In those cell lines, viability decreased significantly (up to 50 %). Responding cell lines were subjected to combination therapy experiments to test if any additive or even synergistic effects may be achieved. Such promising results were obtained in 2/3 cases. In cell lines HROG02, HROG05 and HROG10, ADI and Palomid 529 combinations were most effective yielding more than 70 % killing after 2 rounds of treatment. Comparable boosted antitumoral effects were observed after adding chloroquine to ADI (>60% killing). Apoptosis, as well as cell cycle dysregulation were found to play a minor role. In some, but clearly not all cases, (epi-) genetic silencing of arginine synthesis pathway genes (argininosuccinate synthetase 1 and argininosuccinate lyase) explained obtained results. In vivo, ADI as well as the combination of ADI and SAHA efficiently controlled HROG05 xenograft growth, whereas adding Palomid 529 to ADI did not further increase the strong antitumoral effect of ADI. The cumulative in vitro and in vivo results proved ADI as a very promising candidate therapeutic, especially for development of adjuvant GBM combination treatments.

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Section: Methodsmentioning

confidence: 99%

Arginine deprivation by arginine deiminase ofStreptococcus pyogenescontrols primary glioblastoma growthin vitroandin vivo

Fiedler

Strauss

Hering

et al. 2015

Cancer Biology & Therapy

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“…Hence, arginine-degrading enzymes are currently the most promising approach to arginine deprivation therapy. Therapeutically relevant argininedegrading enzymes include (1) arginase 1 catabolizing arginine to ornithine, (2) arginine decarboxylase (ADC) decarboxylating arginine to agmatine and CO 2 , and (3) arginine deiminase (ADI) degrading arginine to citrulline and ammonia [19,30,46]. The potential of each of these enzymes for arginine degradation not only depends on their efficiency, but also on their immunogenicity, catabolic products as well as stability in patients.…”

Section: Strategies For Arginine-deprivation Therapy -Experimental Apmentioning

confidence: 99%

“…However, the reaction optima of ADIs from some species fit well with the conditions in humans. Among those are ADI from Streptococcus pyogenes, Pseudomonas plecoglossicida or Mycoplasma species, having their temperature optimum at around 37 °C and their pH optimum in the neutral to slightly acidic range, which corresponds to conditions in the microenvironment of solid tumors [46,47]. Due to the high affinity to arginine, ADI derived from Mycoplasma species are by far best investigated and are the most frequently applied enzymes in experimental and clinical studies.…”

Section: Adimentioning

confidence: 99%

Arginine-Depleting Enzymes – An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies

Riess

Shokraie

Classen

et al. 2018

Cell Physiol Biochem

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Arginine auxotrophy occurs in certain tumor types and is usually caused by the silencing of argininosuccinate synthetase 1 or arginine lyase genes. Such tumors are often associated with an intrinsic chemoresistance and thus a poor prognosis. Arginine auxotrophy however renders these tumors vulnerable to treatment with arginine-degrading enzymes. Among the most frequently applied arginine-degrading agents are bacterial arginine deiminases (ADI). The anti-cancerous effects of ADI derived from different bacteria were extensively studied in numerous preclinical cell culture and xenograft models. Mycoplasma-derived ADI-PEG20 is most commonly used and is currently under clinical investigation as a single agent therapeutic as well as in combination with different antineoplastic compounds. Mechanistically, ADI is capable of reducing metabolic activity in tumor cells, contributing to autophagy, senescence and apoptosis in arginine auxotrophic cells. Although clinical trials are promising, the resistance development upon initial treatment response is an increasing challenge. Furthermore, interference of ADI with the tumor microenvironment is poorly understood. In the present review, we outline recent experimental ADI-based treatment approaches and their translation into the clinic. Furthermore, we summarize new insights into the molecular mechanisms underlying the anti-cancer effects of ADI that might facilitate the refinement of ADI-based combination therapy approaches.

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“…2 oxoisovalerate dehydrogenase subunit alpha is part of a large protein complex in the TCA cycle, and is responsible for the conversion of alpha-keto acids to acetyl-CoA [32]. Carbamate kinase is responsible for transferring a phosphate from carbamoyl phosphate to ADP thereby generating ATP [33]. NH3 dependent NAD synthetase is responsible for the final step in generating NAD+ from deamindo-NAD+ [34].…”

Section: Resultsmentioning

confidence: 99%

Discovery of genes encoding a Streptolysin S-like toxin biosynthetic cluster in a select highly pathogenic methicillin resistantStaphylococcus aureusJKD6159 strain

Kane

Yang

et al. 2019

Preprint

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21Background: Staphylococcus aureus (S. aureus) is a major human pathogen owing to 22 its arsenal of virulence factors, as well as its acquisition of multi-antibiotic resistance. 23Here we report the identification of a Streptolysin S (SLS) like biosynthetic gene cluster 24 in a highly virulent community-acquired methicillin resistant S. aureus (MRSA) isolate, 25 JKD6159. Examination of the SLS-like gene cluster in JKD6159 shows significant 26 homology and gene organization to the SLS-associated biosynthetic gene (sag) cluster 27 responsible for the production of the major hemolysin SLS in Group A Streptococcus. 28 Results: We took a comprehensive approach to elucidating the putative role of the sag 29 gene cluster in JKD6159 by constructing a mutant in which one of the biosynthesis 30 genes (sagB homologue) was deleted in the parent JKD6159 strain. Assays to evaluate 31 bacterial gene regulation, biofilm formation, antimicrobial activity, as well as complete 32 host cell response profile and comparative in vivo infections in Balb/Cj mice were 33 conducted. 34 Conclusions: Although no significant phenotypic changes were observed in our 35assays, we postulate that the SLS-like toxin produced by this strain of S. aureus may be 36 a highly specialized virulence factor utilized in specific environments for selective 37 advantage; studies to better understand the role of this newly discovered virulence 38 factor in S. aureus warrant further investigation. 39

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Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49

Cited by 21 publications

References 56 publications

Arginine deprivation by arginine deiminase ofStreptococcus pyogenescontrols primary glioblastoma growthin vitroandin vivo

Arginine deprivation by arginine deiminase ofStreptococcus pyogenescontrols primary glioblastoma growthin vitroandin vivo

Arginine-Depleting Enzymes – An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies

Discovery of genes encoding a Streptolysin S-like toxin biosynthetic cluster in a select highly pathogenic methicillin resistantStaphylococcus aureusJKD6159 strain

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