Monkeypox is an infectious zoonotic disease caused by an Orthopoxvirus and results in symptoms similar to smallpox. In a recent outbreak, monkeypox virus (MPXV) cases have been reported globally since May 2022, and the numbers are increasing. Monkeypox was first diagnosed in humans in the Democratic Republic of Congo and has now spread to throughout Europe, the USA, and Africa. In this study, we analyzed the whole genome sequences of MPXV sequences from recent outbreaks in various countries and performed phylogenomic analysis. Our analysis of the available human MPXV strains showed the highest mutations per sample in 2022 with the average number of mutations per sample being the highest in South America and the European continents in 2022. We analyzed specific mutations in 11 Indian MPXV strains occurring in the variable end regions of the MPXV genome, where the mutation number was as high as 10 mutations per gene. Among these, envelope glycoproteins, the B2R protein, the Ankyrin repeat protein, DNA polymerase, and the INF alpha receptor-like secreted glycoprotein were seen to have a relatively high number of mutations. We discussed the stabilizing effects of the mutations in some of the highly mutating proteins. Our results showed that the proteins involved in binding to the host receptors were mutating at a faster rate, which empowered the virus for active selection towards increased disease transmissibility and severity.

Polyamines are poly-cationic molecules ubiquitously present in all organisms. Salmonella synthesizes and also harbors specialized ABC transporters to uptake polyamines. Polyamines assist in pathogenesis and stress resistance in Salmonella; however, the mechanism remains elusive. The virulence trait of Salmonella depends on the injection of effector proteins into the host cell and modulation of host machinery and employs an array of arsenals to colonize in the host niche successfully. However, prior to this, Salmonella utilizes multiple surface structures to attach and adhere to the surface of the target cells. Our study solves the enigma of how polyamine spermidine assists in the pathogenesis of Salmonella. We show that spermidine mediates the initial attachment and adhesion of Salmonella Typhimurium to Caco-2 cells, facilitating its invasion. In-vivo studies showed that polyamines are required for invasion into the murine Peyers patches. Polyamines have previously been shown to regulate the transcription of multiple genes in both eukaryotes and prokaryotes. We show that spermidine controls the RNA expression of the two-component system, BarA/SirA, that further regulates multiple fimbrial and non-fimbrial adhesins in Salmonella. Flagella is also a vital surface structure aiding in motility and attachment to surfaces of host cells and gall stones. Spermidine regulated the expression of flagellin genes by enhancing the translation of sigma28, 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 Salmonella pathogenicity island-1 encoded genes. Thus, our study unravels a novel mechanism by which spermidine aids in the adhesion and the subsequent invasion of Salmonella into host cells.