Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

Jacob, J. J.; Pragasam, A. K.; Vasudevan, K.; V, A.; Priya T, M.; Priya T, T.; Ray, P.; Gupta, M.; Kapil, A.; Bai, S. P.; Nagaraj, S.; Saigal, K.; Chandola, T. R.; Thomas, M.; Bavdekar, A.; Ebenezer, S. E.; Shastri, J.; De, A.; Dutta, S.; Alexander, A. P.; Koshy, R. M.; Jinka, D. R.; Singh, A. W.; Srivastava, S. K.; Anandan, S.; Dougan, G.; John, J.; Kang, G.; Veeraraghavan, B.; Mutreja, A.

doi:10.1101/2022.06.09.495420

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bioRxiv · 10.1101/2022.06.09.495420

Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

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Abstract

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of Asia and Sub-Saharan Africa. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis documented that the genome degradation events and gene acquisitions or losses play a major role in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 pseudogene-forming mutations possibly associated with the emergence of lineages were identified. Pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We also identified that the six characteristic missense mutations associated with the lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A confer only a low structural impact and would therefore have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and intervention by means of genomic surveillance would be continually needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

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Jacob, J. J., Pragasam, A. K., Vasudevan, K., V, A., Priya T, M., Priya T, T., Ray, P., Gupta, M., Kapil, A., Bai, S. P., Nagaraj, S., Saigal, K., Chandola, T. R., Thomas, M., Bavdekar, A., Ebenezer, S. E., Shastri, J., De, A., Dutta, S., Alexander, A. P., Koshy, R. M., Jinka, D. R., Singh, A. W., Srivastava, S. K., Anandan, S., Dougan, G., John, J., Kang, G., Veeraraghavan, B., Mutreja, A.. 2022-06-10. Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages. https://doi.org/10.1101/2022.06.09.495420

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