Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences

Kawatra, Anubhuti; Dhankhar, Rakhi; Gulati, Pooja

doi:10.1016/j.ijbiomac.2021.12.015

Cited by 14 publications

(4 citation statements)

References 94 publications

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“…While Arg-deprived, non-cancer cells undergo quiescence and cycle arrest at G0/G1 phase, cancer cells starved for Arg continue instead to DNA synthesis, leading to unbalanced growth and ultimately to cell death [ 63 ]. Currently, ARGase, as a PEGylated derivative, is employed in clinical trials for the treatment of HCC, melanoma, prostate adenocarcinoma, and pediatric acute myeloid leukemia (AML), while trials with PEGylated ADI are ongoing for the treatment of small cell lung cancer, melanoma, AML, HCC, and mesothelioma [ 64 ].…”

Section: Introductionmentioning

confidence: 99%

Amino Acids in Cancer and Cachexia: An Integrated View

Ragni

Fornelli

Nisoli

et al. 2022

Cancers

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Rapid tumor growth requires elevated biosynthetic activity, supported by metabolic rewiring occurring both intrinsically in cancer cells and extrinsically in the cancer host. The Warburg effect is one such example, burning glucose to produce a continuous flux of biomass substrates in cancer cells at the cost of energy wasting metabolic cycles in the host to maintain stable glycemia. Amino acid (AA) metabolism is profoundly altered in cancer cells, which use AAs for energy production and for supporting cell proliferation. The peculiarities in cancer AA metabolism allow the identification of specific vulnerabilities as targets of anti-cancer treatments. In the current review, specific approaches targeting AAs in terms of either deprivation or supplementation are discussed. Although based on opposed strategies, both show, in vitro and in vivo, positive effects. Any AA-targeted intervention will inevitably impact the cancer host, who frequently already has cachexia. Cancer cachexia is a wasting syndrome, also due to malnutrition, that compromises the effectiveness of anti-cancer drugs and eventually causes the patient’s death. AA deprivation may exacerbate malnutrition and cachexia, while AA supplementation may improve the nutritional status, counteract cachexia, and predispose the patient to a more effective anti-cancer treatment. Here is provided an attempt to describe the AA-based therapeutic approaches that integrate currently distant points of view on cancer-centered and host-centered research, providing a glimpse of several potential investigations that approach cachexia as a unique cancer disease.

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Section: Introductionmentioning

confidence: 99%

Amino Acids in Cancer and Cachexia: An Integrated View

Ragni

Fornelli

Nisoli

et al. 2022

Cancers

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“…Pegylated recombinant mycoplasma ADI (ADI-PEG 20) is in the last phase of clinical trials against various arginine auxotrophic cancers, such as hepatocellular carcinoma, melanoma, and mesothelioma [75]. Recently, ADI has become of great importance in the treatment of Alzheimer's disease and antiviral drugs [76]. Arginine catabolism with ADI-PEG 20 is considered a promising method of obesity treatment and related disorders [77].…”

Section: Discussionmentioning

confidence: 99%

Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro

Starikova,

Mammedova,

Ozhiganova

et al. 2023

Microorganisms

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Pathogenic microbes use arginine-metabolizing enzymes as an immune evasion strategy. In this study, the impact of streptococcal arginine deiminase (ADI) on the human peripheral blood T lymphocytes function in vitro was studied. The comparison of the effects of parental strain (Streptococcus pyogenes M49-16) with wild type of ArcA gene and its isogenic mutant with inactivated ArcA gene (Streptococcus pyogenes M49-16delArcA) was carried out. It was found that ADI in parental strain SDSC composition resulted in a fivefold decrease in the arginine concentration in human peripheral blood mononuclear cell (PBMC) supernatants. Only parental strain SDSCs suppressed anti-CD2/CD3/CD28-bead-stimulated mitochondrial dehydrogenase activity and caused a twofold decrease in IL-2 production in PBMC. Flow cytometry analysis revealed that ADI decreased the percentage of CM (central memory) and increased the proportion of TEMRA (terminally differentiated effector memory) of CD4+ and CD8+ T cells subsets. Enzyme activity inhibited the proliferation of all CD8+ T cell subsets as well as CM, EM (effector memory), and TEMRA CD4+ T cells. One of the prominent ADI effects was the inhibition of autophagy processes in CD8+ CM and EM as well as CD4+ CM, EM, and TEMRA T cell subsets. The data obtained confirm arginine’s crucial role in controlling immune reactions and suggest that streptococcal ADI may downregulate adaptive immunity and immunological memory.

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“… 87 Importantly, microbial ADI moved also into the focus of interest because of its therapeutic potential against auxotrophic tumors. 88 …”

Section: Microbial L-arg Metabolismmentioning

confidence: 99%

L-arginine metabolism as pivotal interface of mutual host–microbe interactions in the gut

et al. 2023

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L-arginine (L-arg) is a versatile amino acid and a central intestinal metabolite in mammalian and microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways in the regulation of cell division and growth. It also serves as a source of carbon, nitrogen, and energy or as a substrate for protein synthesis. Consequently, L-arg can simultaneously modify mammalian immune functions, intraluminal metabolism, intestinal microbiota, and microbial pathogenesis. While dietary intake, protein turnover or de novo synthesis usually supply L-arg in sufficient amounts, the expression of several key enzymes of L-arg metabolism can change rapidly and dramatically following inflammation, sepsis, or injury. Consequently, the availability of L-arg can be restricted due to increased catabolism, transforming L-arg into an essential amino acid. Here, we review the enzymatic pathways of L-arg metabolism in microbial and mammalian cells and their role in immune function, intraluminal metabolism, colonization resistance, and microbial pathogenesis in the gut.

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Microbial arginine deiminase: A multifaceted green catalyst in biomedical sciences

Cited by 14 publications

References 94 publications

Amino Acids in Cancer and Cachexia: An Integrated View

Amino Acids in Cancer and Cachexia: An Integrated View

Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro

L-arginine metabolism as pivotal interface of mutual host–microbe interactions in the gut

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