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KMID : 0880220190570010064
Journal of Microbiology
2019 Volume.57 No. 1 p.64 ~ p.73
Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr
Zhi Yong

Lin Shun Mei
Jang A-Yeung
Ahn Ki-Bum
Ji Hyun-Jung
Guo Hui-Chen
Lim Sang-Yong
Seo Ho-Seong
Abstract
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 (¥ÄptsI¥Äcrr) 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.
KEYWORD
Salmonella Typhimurium, phosphotransferase system, live attenuation vaccine
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