Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis

Datey, Akshay and Shreenivas, Meghanashree and Chandrasekharan, Giridhar and Joseph, Jeswin and Sah, Shivjee and Aluri, Srinivas and Saha, Sankhanil and Varshney, Umesh and Chakravortty, Dipshikha (2018) Rewiring of one carbon metabolism in Salmonella serves as an excellent live vaccine against systemic salmonellosis. In: VACCINE, 36 (50). pp. 7715-7727.

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Abstract

Live attenuated vaccines are superior to the killed or subunit vaccines. We designed a Salmonella Typhimurium strain by deleting folD gene (encoding methylenetetrahydrofolate dehydrogenasecy-clohydrolase) in the presence of a heterologous fhu gene (encoding formyltetrahydrofolate synthetase) and tested its vaccine potential under stringent conditions of lethal and sub-lethal challenges with virulent Salmonella in the murine model. The efficacy of the vaccine in conferring protection against Salmonella infection was determined in a wide range of host conditions of systemic infection, corresponding to human young adults, neonates, geriatric age and, importantly, to the immune compromised state of pregnancy. The standardized vaccination regime comprised a primary dose of 10(4) CFU/animal followed by a booster dose of 10(2) CFU/animal on day 7. Challenge with the virulent pathogen was done at day 7 post-administration of the booster. Subsequently, the mortality, morbidity, systemic colonization, antibody response and cytokine profiling were determined. The vaccinated cohort showed a strong protection against virulent pathogen in all models tested. The serum anti-Salmonella antibody titers and cytokine levels were significantly higher in the vaccinated cohort compared to the mock vaccinated cohort. Thus, we report the development and validation of a live attenuated vaccine candidate conferring excellent protection against Salmonellosis and typhoid fever. (C) 2018 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Publication:	VACCINE
Publisher:	ELSEVIER SCI LTD
Additional Information:	Copyright of this information belongs to ELSEVIER SCI LTD
Keywords:	Salmonella Typhimurium; One-carbon metabolism; Live attenuated vaccine; Murine model; Systemic salmonellosis
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Aerospace Engineering(Formerly Aeronautical Engineering)
Date Deposited:	28 Jan 2019 09:36
Last Modified:	28 Jan 2019 09:36
URI:	http://eprints.iisc.ac.in/id/eprint/61498

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