Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr

Yong Zhi; Shun Mei Lin; A-Yeung Jang; Ki Bum Ahn; Hyun Jung Ji; Hui-Chen Guo; Sangyong Lim; Ho Seong Seo

doi:10.1007/s12275-019-8416-0

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Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr: Yong Zhi ^1,2, Shun Mei Lin ¹, A-Yeung Jang ^1,3, Ki Bum Ahn ¹, Hyun Jung Ji ^1,4, Hui-Chen Guo ⁵, Sangyong Lim ^1,2, Ho Seong Seo ^1,2; Journal of Microbiology 2019;57(1):64-73.
DOI: https://doi.org/10.1007/s12275-019-8416-0
Published online: October 2, 2018

¹Radiation Biotechnology Division, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea, ²Department of Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology, Daejeon 34113, Republic of Korea, ³Department of Biological Sciences, Chonbuk National University, Jeonju 54896, Republic of Korea, ⁴Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea, ⁵State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, P. R. China¹Radiation Biotechnology Division, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea, ²Department of Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology, Daejeon 34113, Republic of Korea, ³Department of Biological Sciences, Chonbuk National University, Jeonju 54896, Republic of Korea, ⁴Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea, ⁵State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, P. R. China

Corresponding author: Sangyong Lim , Tel: +82-63-570-3141,
Ho Seong Seo , Tel: +82-63-570-3141,

Received: 1 August 2018 • Revised: 20 September 2018 • Accepted: 2 October 2018

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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 (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.

Keywords: Salmonella Typhimurium;phosphotransferase system;live attenuation vaccine

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Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr

J. Microbiol. 2019;57(1):64-73. Published online October 2, 2018

DOI: https://doi.org/10.1007/s12275-019-8416-0

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