bims-polyam 2024-01-21 papers

Issue of 2024–01–21
four papers selected by
Sebastian J. Hofer, University of Graz

Microbiol Res. 2024 Jan 12. pii: S0944-5013(24)00006-5. [Epub ahead of print]281 127605

Spermidine constitutes a key determinant of motility and attachment of Salmonella Typhimurium through a novel regulatory mechanism.

Abhilash Vijay Nair, Anmol Singh, Yashas Devasurmutt, S A Rahman, Utpal Shashikant Tatu, Dipshikha Chakravortty.

Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer's patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis.

Keywords: Adhesins; Flagella; Intestinal epithelial cells; Sigma-factor(28)Salmonella- pathogenicity island-1; Spermidine

DOI: https://doi.org/10.1016/j.micres.2024.127605

Biotechnol Appl Biochem. 2024 Jan 15.

Enzymatic properties of ornithine decarboxylase from Clostridium aceticum DSM1496.

Qian Tan, Linbo Gou, Tai-Ping Fan, Yujie Cai.

Clostridium aceticum DSM1496 is an acid-resistant strain in which ornithine decarboxylase (ODC) plays a crucial role in acid resistance. In this study, we expressed ODC derived from C. aceticum DSM1496 in Escherichia coli BL21 (DE3) and thoroughly examined its enzymatic properties. The enzyme has a molecular weight of 55.27 kDa and uses pyridoxal-5'-phosphate (PLP) as a coenzyme with a Km = 0.31 mM. ODC exhibits optimal activity at pH 7.5, and it maintains high stability even at pH 4.5. The peak reaction temperature for ODC is 30°C. Besides, it can be influenced by certain metal ions such as Mn2+ . Although l-ornithine serves as the preferred substrate for ODC, the enzyme also decarboxylates l-arginine and l-lysine simultaneously. The results indicate that ODC derived from C. aceticum DSM1496 exhibits the ability to produce putrescine, cadaverine, and agmatine through decarboxylation. These polyamines have the potential to neutralize acid in an acidic environment, facilitating the growth of microorganisms. These significant findings provide a strong basis for further investigation into the acid-resistant mechanisms contributed by ODC.

Keywords: Clostridium aceticum DSM1496; ODC; characterization; polyamines

DOI: https://doi.org/10.1002/bab.2556

Nat Metab. 2024 Jan 19.

Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing.

Jengmin Kang, Daniel I Benjamin, Soochi Kim, Jayesh S Salvi, Gurkamal Dhaliwal, Richard Lam, Armon Goshayeshi, Jamie O Brett, Ling Liu, Thomas A Rando.

The global loss of heterochromatin during ageing has been observed in eukaryotes from yeast to humans, and this has been proposed as one of the causes of ageing. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di/tri-methylation and HP1, decrease with age in muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor S-adenosylmethionine (SAM). We find that restoration of intracellular SAM in aged MuSCs restores heterochromatin content to youthful levels and rejuvenates age-associated features, including DNA damage accumulation, increased cell death, and defective muscle regeneration. SAM is not only a methyl group donor for transmethylation, but it is also an aminopropyl donor for polyamine synthesis. Excessive consumption of SAM in polyamine synthesis may reduce its availability for transmethylation. Consistent with this premise, we observe that perturbation of increased polyamine synthesis by inhibiting spermidine synthase restores intracellular SAM content and heterochromatin formation, leading to improvements in aged MuSC function and regenerative capacity in male and female mice. Together, our studies demonstrate a direct causal link between polyamine metabolism and epigenetic dysregulation during murine MuSC ageing.

DOI: https://doi.org/10.1038/s42255-023-00955-z