bims-polyam 2019-08-18 papers

on Polyamines

Issue of 2019–08–18
six papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

Short-chain diamines are the physiological substrates of PACE family efflux pumps.
Spermine Confers Stress Resilience by Modulating Abscisic Acid Biosynthesis and Stress Responses in Arabidopsis Plants.
Transcriptome Analysis of Acid-Responsive Genes and Pathways Involved in Polyamine Regulation in Iron Walnut.
Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling.
24-epibrassinolide and spermidine alleviate Mn stress via the modulation of root morphology, stomatal behavior, photosynthetic attributes and antioxidant defense in Brassica juncea.
Clinical and cranial MRI features of female patients with ornithine transcarbamylase deficiency: Two case reports.

Proc Natl Acad Sci U S A. 2019 Aug 15. pii: 201901591. [Epub ahead of print]

Short-chain diamines are the physiological substrates of PACE family efflux pumps.

Karl A Hassan, Varsha Naidu, Jacob R Edgerton, Karla A Mettrick, Qi Liu, Leila Fahmy, Liping Li, Scott M Jackson, Irshad Ahmad, David Sharples, Peter J F Henderson, Ian T Paulsen.

  Acinetobacter baumannii has rapidly emerged as a major cause of gram-negative hospital infections worldwide. A. baumannii encodes for the transport protein AceI, which confers resistance to chlorhexidine, a widely used antiseptic. AceI is also the prototype for the recently discovered proteobacterial antimicrobial compound efflux (PACE) family of transport proteins that confer resistance to a range of antibiotics and antiseptics in many gram-negative bacteria, including pathogens. The gene encoding AceI is conserved in the core genome of A. baumannii, suggesting that it has an important primordial function. This is incongruous with the sole characterized substrate of AceI, chlorhexidine, an entirely synthetic biocide produced only during the last century. Here we investigated a potential primordial function of AceI and other members of the PACE family in the transport of naturally occurring polyamines. Polyamines are abundant in living cells, where they have physiologically important functions and play multifaceted roles in bacterial infection. Gene expression studies revealed that the aceI gene is induced in A. baumannii by the short-chain diamines cadaverine and putrescine. Membrane transport experiments conducted in whole cells of A. baumannii and Escherichia coli and also in proteoliposomes showed that AceI mediates the efflux of these short-chain diamines when energized by an electrochemical gradient. Assays conducted using 8 additional diverse PACE family proteins identified 3 that also catalyze cadaverine transport. Taken together, these results demonstrate that short-chain diamines are common substrates for the PACE family of transport proteins, adding to their broad significance as a novel family of efflux pumps.

Keywords:  PACE family; drug resistance; efflux; polyamines; transport

DOI:  https://doi.org/10.1073/pnas.1901591116
Front Plant Sci. 2019 ;10 972

Spermine Confers Stress Resilience by Modulating Abscisic Acid Biosynthesis and Stress Responses in Arabidopsis Plants.

Francisco Marco, Enrique Busó, Teresa Lafuente, Pedro Carrasco.

  Polyamines (PAs) constitute a group of low molecular weight aliphatic amines that have been implicated as key players in growth and development processes, as well as in the response to biotic and abiotic stresses. Transgenic plants overexpressing PA-biosynthetic genes show increased tolerance to abiotic stress. Therein, abscisic acid (ABA) is the hormone involved in plant responses to environmental stresses such as drought or high salinity. An increase in the level of free spermine (Spm) in transgenic Arabidopsis plants resulted in increased levels of endogenous ABA and promoted, in a Spm-dependent way, transcription of different ABA inducible genes. This phenotype was only partially reversed by blocking ABA biosynthesis, indicating an ABA independent response mediated by Spm. Moreover, the phenotype was reproduced by adding Spm to Col0 wild-type Arabidopsis plants. In contrast, Spm-deficient mutants showed a lower tolerance to salt stress. These results indicate that Spm plays a key role in modulating plant stress responses.

Keywords:  abscisic acid; salt stress; spermine; stress response; stress tolerance

DOI:  https://doi.org/10.3389/fpls.2019.00972
Genes (Basel). 2019 Aug 10. pii: E605. [Epub ahead of print]10(8):

Transcriptome Analysis of Acid-Responsive Genes and Pathways Involved in Polyamine Regulation in Iron Walnut.

Xiaomei Luo, Juncheng Liu.

  We reported changes in the co-regulated mRNA expression in iron walnut (Juglans sigillata) in response to soil pH treatments and identified mRNAs specific to acidic soil conditions. Phenotypic and physiological analyses revealed that iron walnut growth was greater for the pH 4-5 and pH 5-6 treatments than for the pH 3-4 and pH 6-7 treatments. A total of 2768 differentially expressed genes were detected and categorized into 12 clusters by Short Time-series Expression Miner (STEM). The 994 low-expression genes in cluster III and 255 high-expression genes in cluster X were classified as acid-responsive genes on the basis of the relationships between phenotype, physiology, and STEM clustering, and the two gene clusters were analyzed by a maximum likelihood (ML) evolutionary tree with the greatest log likelihood values. No prominent sub-clusters occurred in cluster III, but three occurred in cluster X. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that acid-responsive genes were related primarily to arginine biosynthesis and the arginine/proline metabolism pathway, implying that polyamine accumulation may enhance iron walnut acid stress tolerance. Overall, our results revealed 1249 potentially acid-responsive genes in iron walnut, indicating that its response to acid stress involves different pathways and activated genes.

Keywords:  RNA-seq; Short Time-series Expression Miner (STEM) analysis; acid soil stress; chlorophyll; photosynthesis

DOI:  https://doi.org/10.3390/genes10080605
Front Oncol. 2019 ;9 681

Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling.

Cheng Zhang, Mohammed Aldrees, Muhammad Arif, Xiangyu Li, Adil Mardinoglu, Mohammad Azhar Aziz.

  Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.

Keywords:  colorectal cancer; genome scale metabolic model; personalized medicine; polyamine metabolism; transcriptomics

DOI:  https://doi.org/10.3389/fonc.2019.00681
Physiol Mol Biol Plants. 2019 Jul;25(4): 905-919

24-epibrassinolide and spermidine alleviate Mn stress via the modulation of root morphology, stomatal behavior, photosynthetic attributes and antioxidant defense in Brassica juncea.

Anjuman Hussain, Faroza Nazir, Qazi Fariduddin.

  Brassinosteroids and polyamines are generally used to surpass different abiotic stresses like heavy metal toxicity in plants. The current study was conducted with an aim that 24-epibrassinolide (EBL) and/or spermidine (Spd) could modify root morphology, movement of stomata, cell viability, photosynthetic effectiveness, carbonic anhydrase and antioxidant enzyme activities in Brassica juncea under manganese (Mn) stress (30 or 150 mg kg-1 soil). EBL (10-8 M) and/or Spd, (1.0 mM) were applied to the foliage of B. juncea plants at 35 days after sowing (DAS), grown in the presence of Mn (30 or 150 mg kg-1 soil). High Mn concentration (150 mg kg-1 soil) altered root morphology, affected stomatal movement, reduced the viability of cells and photosynthetic effectiveness and increased the production of reactive oxygen species (O2 ·- and H2O2) in the leaves and antioxidant defense system of B. juncea at 45 DAS. Furthermore, exogenous treatment of EBL and Spd under stress and stress- free conditions improved the aforesaid traits while decreased the O2 ·- and H2O2 production. Therefore, EBL and Spd could be applied to the foliage of B. juncea plants for the better growth under metal stress.

Keywords:  Epibrassinolide; Manganese; Photosynthesis; Root morphology; Spermidine; Stomata

DOI:  https://doi.org/10.1007/s12298-019-00672-6
Medicine (Baltimore). 2019 Aug;98(33): e16827

Clinical and cranial MRI features of female patients with ornithine transcarbamylase deficiency: Two case reports.

Dan Yu, Guoyan Lu, Rajah Mowshica, Yan Cheng, Fumin Zhao.

INTRODUCTION: Ornithine transcarbamylase deficiency (OTCD) is a common metabolic disease of urea circulation disorder. We reported the clinical, brain imaging and genetic characteristics of 2 cases with OTCD. The patients' clinical features, novel gene mutations, cranial MR specific imaging changes and blood tandem mass spectrometry, and urine gas chromatography-mass spectrometry were, retrospectively, analyzed.
PATIENT CONCERNS: Patient 1 was a 1.6-year-old female. She was admitted to the hospital with 2-months history of general irritability and disturbance of consciousness for a day. Patient 2 was a 3.7-year-old female. She was admitted to the hospital due to decline of language ability and irritability for 5 days. Blood tandem mass spectrometry and urine gas chromatography-mass spectrometry showed uracil and orotate increased significantly in urine while amino acids in the urea cycle ring were in the normal range. The features of brain MRI are consistent with those of urea circulatory disorders. Gene detection showed 1 novel mutation in the OTC gene (c.658C>T) in patient 1 and, 1 novel mutation (c.298+2T>G) in the OTC gene in patient 2.
DIAGNOSIS: Combined with metabolic screening and gene detection, both patients were diagnosed with OTCD.
INTERVENTIONS: The patients' condition improved after following a low protein diet and receiving treatments for decreasing blood ammonia, energy supplement, correcting acid-base imbalance, and other symptomatic treatments.
OUTCOMES: After prompt symptomatic treatment, the consciousness and cognition of the children improved. Besides, liver function also improved significantly.
CONCLUSIONS: For patients with neurological symptoms and unexplained increase in transaminase and ammonia, OTCD should be considered as a possible diagnosis. Brain MRI can help the diagnosis of genetic metabolic encephalopathy and reflect the level of brain injury. Metabolic screening and genetic detection are helpful to make a confirmed diagnosis.

DOI: https://doi.org/10.1097/MD.0000000000016827