Of a Tenacious and Versatile Relic: The Role of Inorganic Polyphosphate (Poly-P) Metabolism in the Survival, Adaptation, and Virulence ofCampylobacter Jejuni

Author(s):  
Issmat I. Kassem ◽  
Gireesh Rajashekara
2016 ◽  
Vol 44 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Cristina Azevedo ◽  
Adolfo Saiardi

Post-translational modifications (PTMs) add regulatory features to proteins that help establish the complex functional networks that make up higher organisms. Advances in analytical detection methods have led to the identification of more than 200 types of PTMs. However, some modifications are unstable under the present detection methods, anticipating the existence of further modifications and a much more complex map of PTMs. An example is the recently discovered protein modification polyphosphorylation. Polyphosphorylation is mediated by inorganic polyphosphate (polyP) and represents the covalent attachment of this linear polymer of orthophosphate to lysine residues in target proteins. This modification has eluded MS analysis as both polyP itself and the phosphoramidate bonds created upon its reaction with lysine residues are highly unstable in acidic conditions. Polyphosphorylation detection was only possible through extensive biochemical characterization. Two targets have been identified: nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1). Polyphosphorylation occurs within a conserved N-terminal polyacidic serine (S) and lysine (K) rich (PASK) cluster. It negatively regulates Nsr1–Top1 interaction and impairs Top1 enzymatic activity, namely relaxing supercoiled DNA. Modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. Here we discuss the significance of the recently identified new role of inorganic polyP.


Author(s):  
Alexander Tomashevsky ◽  
Ekaterina Kulakovskaya ◽  
Ludmila Trilisenko ◽  
Tatiana Kulakovskaya ◽  
Alexey Fedorov ◽  
...  

Inorganic polyphosphate (polyP) is an important factor of stress tolerance in microbial cells. In yeast, the major enzyme of polyP biosynthesis is Vtc4, a subunit of the vacuole transporter chaperone (VTC) complex. In this study, we demonstrated that Vtc4 knockout in Saccharomyces cerevisiae not only decreased polyP content but also caused shifts in the composition of the intracellular polyP pool and changed the stress tolerance profile. In the mutant S. cerevisiae, the level of short-chain acid-soluble polyPs was decreased nearly 10-fold, whereas that of longer acid-insoluble polyPs was decreased only 2-fold, suggesting the existence of other enzymes compensating the production of long-chain polyPs. The Δvtc4 mutant showed inhibition of Mg2+-dependent phosphate uptake and decreased resistance to alkaline stress but increased tolerance to oxidation and heavy metal ions, especially Mn2+. Quantitative PCR revealed the upregulation of the DDR2 gene implicated in multiple stress responses and downregulation of PHO84 encoding a phosphate and Mn2+ transporter, which could account for the effects on phosphate uptake and Mn2+-related stress response in the Δvtc4 mutant. Our study indicates that short-chain polyPs, plays an important role in the regulation of stress response in yeast.


Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 461 ◽  
Author(s):  
Ludmila Trilisenko ◽  
Anton Zvonarev ◽  
Airat Valiakhmetov ◽  
Alexey A. Penin ◽  
Irina A. Eliseeva ◽  
...  

Inorganic polyphosphate (polyP) is crucial for adaptive reactions and stress response in microorganisms. A convenient model to study the role of polyP in yeast is the Saccharomyces cerevisiae strain CRN/PPN1 that overexpresses polyphosphatase Ppn1 with stably decreased polyphosphate level. In this study, we combined the whole-transcriptome sequencing, fluorescence microscopy, and polyP quantification to characterize the CRN/PPN1 response to manganese and oxidative stresses. CRN/PPN1 exhibits enhanced resistance to manganese and peroxide due to its pre-adaptive state observed in normal conditions. The pre-adaptive state is characterized by up-regulated genes involved in response to an external stimulus, plasma membrane organization, and oxidation/reduction. The transcriptome-wide data allowed the identification of particular genes crucial for overcoming the manganese excess. The key gene responsible for manganese resistance is PHO84 encoding a low-affinity manganese transporter: Strong PHO84 down-regulation in CRN/PPN1 increases manganese resistance by reduced manganese uptake. On the contrary, PHM7, the top up-regulated gene in CRN/PPN1, is also strongly up-regulated in the manganese-adapted parent strain. Phm7 is an unannotated protein, but manganese adaptation is significantly impaired in Δphm7, thus suggesting its essential function in manganese or phosphate transport.


2014 ◽  
Vol 356 (1) ◽  
pp. 8-19 ◽  
Author(s):  
Christina Bronowski ◽  
Chloe E. James ◽  
Craig Winstanley

2019 ◽  
Vol 662 ◽  
pp. 177-189 ◽  
Author(s):  
Lea K. Seidlmayer ◽  
Maria R. Gomez-Garcia ◽  
Toshikazu Shiba ◽  
George A. Porter ◽  
Evgeny V. Pavlov ◽  
...  

2017 ◽  
Vol 112 (3) ◽  
pp. 439a
Author(s):  
Maria de la Encarnacion Solesio Torregrosa ◽  
Mitchell Marta-Ariza ◽  
Fernando Goni ◽  
Evgeny V. Pavlov

2020 ◽  
Vol 295 (12) ◽  
pp. 4014-4023
Author(s):  
Toru Ito ◽  
Suguru Yamamoto ◽  
Keiichi Yamaguchi ◽  
Mami Sato ◽  
Yoshikatsu Kaneko ◽  
...  

Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate units that are linked by phosphoanhydride bonds and is involved in various pathophysiological processes. However, the role of polyP in immune cell dysfunction is not well-understood. In this study, using several biochemical and cell biology approaches, including cytokine assays, immunofluorescence microscopy, receptor-binding assays with quartz crystal microbalance, and dynamic light scanning, we investigated the effect of polyP on in vitro lipopolysaccharide (LPS)-induced macrophage inflammatory response. PolyP up-regulated LPS-induced production of the inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6, in macrophages, and the effect was polyP dose– and chain length–dependent. However, orthophosphate did not exhibit this effect. PolyP enhanced the LPS-induced intracellular macrophage inflammatory signals. Affinity analysis revealed that polyP interacts with LPS, inducing formation of small micelles, and the polyP-LPS complex enhanced the binding affinity of LPS to Toll-like receptor 4 (TLR4) on macrophages. These results suggest that inorganic polyP plays a critical role in promoting inflammatory response by enhancing the interaction between LPS and TLR4 in macrophages.


2013 ◽  
Vol 90 (4) ◽  
pp. 699-715 ◽  
Author(s):  
Melina Galizzi ◽  
Juan M. Bustamante ◽  
Jianmin Fang ◽  
Kildare Miranda ◽  
Lia C. Soares Medeiros ◽  
...  

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