- Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr
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Yong Zhi , Shun Mei Lin , A-Yeung Jang , Ki Bum Ahn , Hyun Jung Ji , Hui-Chen Guo , Sangyong Lim , Ho Seong Seo
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J. Microbiol. 2019;57(1):64-73. Published online October 2, 2018
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DOI: https://doi.org/10.1007/s12275-019-8416-0
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Abstract
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Salmonella enterica is a major human pathogen that causes
invasive non-typhoidal Salmonellosis (iNTS), resulting in
significant morbidity and mortality. Although a number of
pre-clinical and clinical studies have reported on the feasibility
of developing a safe and effective vaccine against iNTS,
there have been no licensed Salmonella vaccines available to
protect against NTS strains. Vaccine formulations of highest
priority for NTS are live attenuated vaccines, which can elicit
effective induction of intestinal mucosal and intracellular
bacteria-specific cell mediated immune responses. Since glucose
is crucial for intracellular survival and replication in
host cells, we constructed strains with mutations in components
of the glucose uptake system, called the phosphotransferase
system (PTS), and compared the relative virulence and
immune responses in mice. In this study, we found that the
strain with mutations in both ptsI and crr (KST0556) was the
most attenuated strain among the tested strains, and proved
to be highly effective in inducing a mucosal immune response
that can protect against NTS infections in mice. Thus, we suggest
here that KST0556 (ΔptsIΔcrr) is a potential live vaccine
candidate for NTS, and may also be a candidate for a live delivery
vector for heterologous antigens. Moreover, since PTS
is a well-conserved glucose transporter system in both Gramnegative
and Gram-positive bacteria, the ptsI and crr genes
may be potential targets for creating live bacterial vectors or
vaccine strains.
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