Polyamine Metabolism in Fungi with Emphasis on Phytopathogenic Species

Valdés-Santiago, Laura; Cervantes-Chávez, José Antonio; León-Ramírez, Claudia Geraldine; Ruíz-Herrera, José

doi:10.1155/2012/837932

Cited by 60 publications

(67 citation statements)

References 100 publications

(127 reference statements)

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“…Therefore, identification of the route of Hst 5 efflux is crucial for understanding the mechanism for possible Hst 5 resistance. Polyamines are essential aliphatic polycations needed for normal growth and morphogenesis in fungi, so that their depletion results in growth cessation while high intracellular accumulation may be cytotoxic (52). Thus, fungi must strictly regulate their intracellular polyamine pools using membrane-localized polyamine transporter systems that facilitate internalization of exogenous polyamines and excretion of excess intracellular polyamines.…”

Section: Discussionmentioning

confidence: 99%

Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity

Kumar

Tati

et al. 2013

Antimicrob Agents Chemother

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Histatin 5 (Hst 5) is a salivary human antimicrobial peptide that is toxic to the opportunistic yeast Candida albicans. Fungicidal activity of Hst 5 requires intracellular translocation and accumulation to a threshold concentration for it to disrupt cellular processes. Previously, we observed that total cytosolic levels of Hst 5 were gradually reduced from intact cells, suggesting that C. albicans possesses a transport mechanism for efflux of Hst 5. Since we identified C. albicans polyamine transporters responsible for Hst 5 uptake, we hypothesized that one or more polyamine efflux transporters may be involved in the efflux of Hst 5. C. albicans FLU1 and TPO2 were found to be the closest homologs of Saccharomyces cerevisiae TPO1, which encodes a major spermidine efflux transporter, indicating that the products of these two genes may be involved in efflux of Hst 5. We found that flu1⌬/⌬ cells, but not tpo2⌬/⌬ cells, had significant reductions in their rates of Hst 5 efflux and had significantly higher cytoplasmic Hst 5 and Hst 5 susceptibilities than did the wild type. We also found that flu1⌬/⌬ cells had reduced biofilm formation compared to wild-type cells in the presence of Hst 5. Transcriptional levels of FLU1 were not altered over the course of treatment with Hst 5; therefore, Hst 5 is not likely to induce FLU1 gene overexpression as a potential mechanism of resistance. Thus, Flu1, but not Tpo2, mediates efflux of Hst 5 and is responsible for reduction of its toxicity in C. albicans. Candida albicans is a human fungal pathogen that causes serious infections in immunocompromised populations (1-3). In hospitalized patients, this organism can disseminate hematogenously and infect virtually all organs (4-6). The incidence and mortality rates associated with this infectious disease have remained unchanged for more than a decade despite major advances in the field of antifungal therapy (6, 7).Azoles are one of the most widely used groups of antifungal drugs used to treat candidiasis patients and represent a class of five-membered, nitrogen-containing, heterocyclic compounds (8, 9). The azole drugs enter C. albicans cells by facilitated diffusion (10) and inhibit the biosynthesis of ergosterol, which is a major component of C. albicans membranes (11-13). However, the widespread use of azoles coupled with the fungistatic nature of these drugs has led to the emergence of resistance in clinical isolates (8,14,15). Mechanisms of azole resistance include alteration (either by mutation or by overexpression) of the drug target enzyme lanosterol demethylase (encoded by ERG11) and/or constitutive overexpression of multidrug transporters (16).There are two main classes of multidrug transporters that are found to be upregulated in drug-resistant clinical isolates and experimentally evolved populations of C. albicans; these include transporters containing ATP-binding cassettes (ABC) and transporters of the major facilitator superfamily (MFS) (17-20). The ABC transporter superfamily, including Cdr1 and Cdr2, consists of membran...

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Section: Discussionmentioning

confidence: 99%

Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity

Kumar

Tati

et al. 2013

Antimicrob Agents Chemother

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“…Dur3 and Sam3 are predominantly responsible for PA import [110], while Uga4 dominates PA vacuolar transport [111]. Conversely, yeast has four transporters (Tpo1-Tpo4) that function as PA efflux pumps [7,[112][113][114]. Tpo1 and Tpo4 are responsible for the transport of Spd, Spm [115] and Put [116], while Tpo2 and Tpo3 only recognize Spm [115].…”

Section: Controlling Pa Levels Through Transportmentioning

confidence: 99%

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

Miller-Fleming

Olín-Sandoval

Campbell

et al. 2015

Journal of Molecular Biology

540

522

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The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi-directional membrane transport system and a unique posttranslational modification-hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology.

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“…In the study conducted by Santiago et al (2012) they have detected that exogenously applied polyamines may inhibit the micelle growth. In this study, all spermidine and spermidine + proline pre-applications decreased the amount of zoospores and the colony growth compared to the control and 0.1 mM spd, 1 mM spd and 0.1 mM spd + 1 mM proline were determined as the most effective applications.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with spermidine and proline reverses inhibitory effects of Phytophthora capsici stress in pepper

Koç

Arıcı

İşlek

2016

Zemdirbyste-Agriculture

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Phytophthora blight (Phytophthora capsici Leon.), which is one of the most important disease factors incurring great economic losses, causes root crown rot. When pepper seedlings were pretreated with 0.1 mM spermidine (spd), 1 mM spd, 0.1 mM spd + 1 mM proline, 0.1 mM spd + 10 mM proline, 1 mM spd + 1 mM proline and 1 mM spd + 10 mM proline and then exposed to P. capsici, they improved their tolerance to subsequent P. capsici-induced oxidative damage. It was detected that cultivar 'Sirena RZ F1' was resistant to P. capsici and it was determined that cultivar 'Sera Demre-8' exhibited sensitive reaction. P. capsici stress caused an increase in total phenolic, malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ) levels, as well as peroxidase (POX) and polyphenol oxidase (PPO) activities in leaves of pepper seedlings. Application of exogenous spermidine and spermidine + proline further increased PPO and POX activity, total phenolic amount. On the other hand, these applications in two cultivars and all days decreased the disease severity, necrosis length and MDA and H 2 O 2 amounts. These data show that antioxidants, especially polyphenol oxidase, peroxidase and total phenolic appear to protect pepper seedlings against stress-related damage. Moreover, spermidine and spermidine + proline have the potential to scavenge directly free radicals and promote the activity of antioxidant enzymes in pepper seedlings under P. capsici stress. In addition, it was also identified that especially 0.1 mM spd, 1 mM spd and 0.1 mM spd + 1 mM proline applications decreased the colony growth of P. capsici and the amount of zoospores. Therefore, we suggest that spermidine and spermidine + proline could play a protective role in protecting the pepper seedlings from P. capsici stress.

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Polyamine Metabolism in Fungi with Emphasis on Phytopathogenic Species

Cited by 60 publications

References 100 publications

Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity

Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

Pretreatment with spermidine and proline reverses inhibitory effects of Phytophthora capsici stress in pepper

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