Biology subjects

Tatu, U. S.

Publications and source records attributed to Tatu, U. S..

3 recordsLinked to original sources

bioRxiv2023

Unravelling Genomic Origin of Lumpy Skin Disease Virus in Recent Outbreaks

Lumpy skin disease virus (LSDV) belongs to the genus Capripox virus and family Poxviridae. LSDV was endemic in most of Africa, Middle east and Turkey, but since 2015, several outbreaks have been reported in Asian countries. In this study we used Whole Genome Sequence (WGS) approach to investigate the origin of the outbreak and understand the genomic landscape of the virus. Our study showed that the LSDV strain of 2022 outbreak exhibited many genetic variations, compared to the Reference Neethling strain sequence and the previous field strains from India. A total of 1819 variations were found in 22 genome sequences, which includes 399 extragenic mutations, 153 insertion frameshift mutations, 234 deletion frameshift mutations, 271 Single nucleotide polymorphisms (SNPs) and 762 silent SNPs. 38 genes have more than 2 variations per gene and these genes belong to viral-core protein, viral binding proteins, replication and RNA polymerase proteins. We highlight the importance of several SNPs in various genes which may play an essential role in pathogenesis of LSDV. Phylogenetic analysis performed on all whole genome sequences of LSDV showed two types of variants in India. One group of the variant with fewer mutations was found to lie closer to the LSDV 2019 strain from Ranchi while the other group clustered with previous Russian outbreaks from 2015. Our study highlights the importance of genomic characterization of viral outbreaks to not only monitor the frequency of mutations but also address its role in pathogenesis of LSDV as the outbreak continues.

microbiology↗

bioRxiv2023

Spermidine facilitates the adhesion and subsequent invasion of Salmonella Typhimurium into epithelial cells via the regulation of surface adhesive structures and the SPI-1

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 s28, 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.

microbiology↗

bioRxiv2020

Global transcriptional regulation by cell-free supernatant of Salmonella Typhimurium peptide transporter mutant leads to inhibition of intra-species biofilm initiation

Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause [1/4]th of diarrheal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although biofilm removal or dispersal has been studied widely, the inhibition of the initiation of Salmonella biofilm remains elusive. This study was conducted to determine the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation inducible proline peptide transporter mutant ({Delta}yjiY) strain. Our study shows that Salmonella {Delta}yjiY culture supernatant primarily inhibits biofilm initiation by regulating biofilm-associated transcriptional network. This work demonstrates that highly abundant proteases such as HslV and GrpE cleave the protein aggregates, whereas global transcription regulators H-NS, FlgM regulate expression of SPIs and flagellar genes. Relatively low abundances of flavoredoxin, glutaredoxin, thiol peroxidase etc. leads to accumulation of ROS within the biofilm, and subsequent toxicity. This work further suggests that targeting these oxidative stress relieving proteins might be a good druggable choice to reduce Salmonella biofilm. ImportanceThe enteric pathogen Salmonella forms biofilm in the internal organs of asymptomatic carriers, and on abiotic surfaces that leads to contamination of food and water. Biofilms are highly drug-resistant life forms that also helps in host immune evasion. Therefore, recent insurgence of drug tolerant strains necessitates development of biofilm inhibitory strategies, and finding novel druggable targets. In this study we investigated the bioactive molecules present in the cell-free supernatant of a biofilm deficient strain of Salmonella Typhimurium that inhibit biofilm initiation by the wildtype strain. Further we showed that the supernatant treatment leads to virulence defect in vivo. Collectively, our results suggest a comprehensive view of virulence regulation in Salmonella by the cell-free supernatant of the biofilm deficient strain.

microbiology↗