Biology subjects

Chaggar, H. K.

Publications and source records attributed to Chaggar, H. K..

3 recordsLinked to original sources

bioRxiv2025

Phylogeographic clustering of Salmonella enterica serovar Mississippi in the Southeastern United States indicates regional transmission pathways

Salmonella enterica subspecies enterica serovar Mississippi (S. Mississippi) is a polyphyletic serovar endemic in Australia, New Zealand, the United Kingdom, and the United States (USA). From 2018 to 2024, it was the 13th most frequently reported clinical Salmonella serovar in the USA. Its incidence in the USA is geographically focused on the Southeast. From 2018 to 2024, 78% of all S. Mississippi cases in the USA occurred in Southeastern states. The objective of this study was to determine the phylogeographic patterns of clinical S. Mississippi in the Southeastern USA using clinical S. Mississippi isolate sequencing data and metadata from ten state public health laboratories in the region. The resulting phylogeny, based on core single nucleotide polymorphism (SNP) differences, showed that S. Mississippi has five major clades (Ai, Aii, Bi, Bii, C), four of which are consistent with the results of previous studies. Clade Ai, which comprised 99% of study isolates, was systematically divided into seven subclades. County-level mapping of the clade Ai isolates revealed distinct geographical distributions at the clade and subclade levels. For example, subclade Ai1 was predominantly identified along the East Coast, while subclade Ai3 was primarily found in Western Tennessee. Simple linear regression showed a significant positive association (p < 0.01) between isolate-to-isolate genomic distance (SNP differences) and county-to-county geographic distance (km) at the clade and subclade levels. These findings provide insight into the transmission of S. Mississippi and may inform public health hypothesis generation. IMPORTANCEThis study enhances understanding of S. Mississippi transmission pathways and reveals localized phylogeographic clustering within the Southeastern USA. Classification of this serovar with consideration to geographical clustering may improve surveillance, investigation, and control efforts. Geographical clustering of this serovar within this region suggests local or regional transmission pathways and enzootic reservoirs, which could be related to environmental or regional food exposures. Identifying possible environmental sources, enzootic reservoirs, or climate factors contributing to human infection with this serovar within the Southeastern USA could lead to prevention recommendations. Knowledge of exposure patterns for S. Mississippi may facilitate development and implementation of targeted control strategies and interventions locally that can limit further exposure and prevent illness.

genomics↗

bioRxiv2024

Ataxia Telangiectasia patient-derived neuronal and brain organoid models reveal mitochondrial dysfunction and oxidative stress

Ataxia Telangiectasia (AT) is a rare genetic disorder caused by mutations in the ATM gene and is characterized by oxidative stress, premature ageing, and progressive neurodegeneration of the cerebellum. The molecular mechanisms driving the neurological defects AT remain unclear, mainly due to lack of human neuronal models. Here, we use AT patient-derived pluripotent stem cells (iPSCs) and iPSC-derived neurons and brain organoids to comprehensively explore mitochondrial dysfunction, oxidative stress, and senescence phenotypes. We identified mislocalisation of mitochondria, a prevailing reduction in mitochondrial membrane potential, and increased oxidative stress in AT patient-derived iPSC and neuronal cultures that was restored by ATM gene correction. Cortical brain organoids from AT patients also display extensive oxidative stress, increased levels of senescence, and impaired neuronal function that could be counteracted with antioxidant treatment. Transcriptomic analysis identified disruptions in regulatory networks related to mitochondrial function and maintenance, including alterations in the PARP/SIRT signalling axis and dysregulation of key mitophagy and mitochondrial fission-fusion processes. Our study reveals that progressive mitochondrial dysfunction and aberrant ROS production are hallmarks of AT, and lead us to conclude that ATM is a master regulator of mitochondrial homeostasis.

cell biology↗

bioRxiv2022

Phenotypic characterization and analysis of complete genomes of two distinct strains of the proposed species "L. swaminathanii"

Recently, a new Listeria species, "Listeria swaminathanii", was proposed. Here, we phenotypically and genotypically characterize two additional strains that were previously obtained from soil samples and compare the results to the type strain. Complete genomes for both strains were assembled from hybrid Illumina and Nanopore sequencing reads and annotated. Further genomic analysis including average nucleotide identity (ANI) and detection of mobile genetic elements and genes of interest (e.g., virulence-associated) were conducted. The strains showed 98.7-98.8% ANI with the type strain. The UTK C1-0015 genome contained a partial monocin locus and a plasmid while the UTK C1-0024 genome contained a full monocin locus and a prophage. Phenotypic characterization consistent with those performed on the proposed type strain was conducted to assess consistency of phenotypes across a greater diversity of the proposed species (n=3 instead of n=1). Only a few findings were notably different from those of the type strain, such as catalase activity, glycerol metabolism, starch metabolism, and growth at 41{degrees}C. This study further expands our understanding of this newly proposed sensu stricto Listeria species.

microbiology↗