Pan genome clustering identifies a novel mosaic prophage specific to Salmonella Enteritidis lineage associated with the invasive disease in India

@article{jacob2026genome,
  title = {{Pan genome clustering identifies a novel mosaic prophage specific to Salmonella Enteritidis lineage associated with the invasive disease in India}},
  author = {Jobin John Jacob and Aravind Velmurugan and Dhanalakshmi Solaimalai and Ramya Iyadurai and Karthik Gunasekaran and Jansi Rani Malaiyappan and M. Yesudoss and M. Vasuki and Binesh Lal and Jacob John and Kamini Walia and Balaji Veeraraghavan},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = aug,
  doi = {10.1371/journal.pntd.0013113},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013113},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Pan genome clustering identifies a novel mosaic prophage specific to Salmonella Enteritidis lineage associated with the invasive disease in India
AU  - Jobin John Jacob
AU  - Aravind Velmurugan
AU  - Dhanalakshmi Solaimalai
AU  - Ramya Iyadurai
AU  - Karthik Gunasekaran
AU  - Jansi Rani Malaiyappan
AU  - M. Yesudoss
AU  - M. Vasuki
AU  - Binesh Lal
AU  - Jacob John
AU  - Kamini Walia
AU  - Balaji Veeraraghavan
PY  - 2026
DA  - 2026/08/31
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0013113
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013113
AB  - Salmonella enterica serovar Enteritidis is a leading cause of invasive non-typhoidal Salmonella (iNTS) disease globally, particularly in sub-Saharan Africa. In contrast, the epidemiology and population structure of invasive S. Enteritidis in South Asia remain poorly characterized. This study investigates the clinical presentation, phylogenetic relationships and genomic characteristics of S. Enteritidis bloodstream infections (BSIs) in India. Clinical data were collected from 101 patients with S. Enteritidis BSI between 2012 and 2022. Whole-genome sequencing was performed on representative bloodstream isolates together with isolates from non-blood clinical specimens and poultry sources. Comparative genomic analyses included phylogenetic reconstruction, invasiveness index prediction, and prophage characterization. Infants and immunosuppressed individuals were disproportionately affected by iNTS disease. Phylogenetic analysis identified four major lineages of S. Enteritidis. Most BSI isolates clustered in a previously unrecognized lineage, designated the Global Intermediate Clade, which occupied a phylogenetic position between the Global outlier and Global epidemic clades. Bayesian inference dated its most recent common ancestor to around 1789 AD (95% HPD: 1692–1941), with global circulation confirmed by European and Asian isolates. The Global Intermediate clade exhibited the second-highest invasiveness index (median 0.221, SD 0.013) after the West African clade; however, this index reflects genomic signatures associated with invasiveness and should not be interpreted as a direct measure of virulence. Poultry isolates clustered separately from the dominant bloodstream-associated lineage. Pan-genome analysis identified a lineage-specific mosaic prophage composed of modules homologous to prophages found in diverse Enterobacterales. This study provides the first detailed genomic insight into invasive S. Enteritidis in India and identifies a previously unrecognized Global Intermediate Clade associated with bloodstream infection. The distinct phylogenetic placement and genomic features of this lineage, including a lineage-specific mosaic prophage, warrant further investigation and support the need for expanded One Health genomic surveillance. Author summary: Invasive infections caused by Salmonella enterica serovar Enteritidis are a major public health concern in many low- and middle-income countries, yet their epidemiology in South Asia remains poorly understood. We analyzed clinical and genomic data from patients with bloodstream infections caused by S. Enteritidis in India and compared these isolates with strains obtained from poultry and publicly available global genomes. We found that invasive infections occurred most frequently in infants and individuals with immunosuppressive conditions. Genomic analysis identified a previously unrecognized lineage, which we named the Global Intermediate Clade, that accounted for a large proportion of bloodstream isolates in our collection. This lineage occupies a distinct position within the global S. Enteritidis population structure and carries a unique mosaic prophage not observed in other major lineages. Although the Global Intermediate Clade showed a comparatively elevated invasiveness index, this metric is based on genomic prediction and does not directly measure clinical virulence. Poultry isolates from our study were genetically distinct from the dominant bloodstream-associated lineage, although broader animal reservoirs cannot be excluded. Our findings expand current understanding of invasive S. Enteritidis in South Asia and highlight the value of integrated clinical and genomic surveillance for identifying and monitoring previously unrecognized pathogen lineages.
SN  - 1935-2735
ER  -