| Title | Effective mucosal live attenuated Salmonella vaccine by deleting phosphotransferase system component genes ptsI and crr |
|---|---|
| Author | Yong Zhi1,2, Shun Mei Lin1, A-Yeung Jang1,3, Ki Bum Ahn1, Hyun Jung Ji1,4, Hui-Chen Guo5, Sangyong Lim1,2*, and Ho Seong Seo1,2* |
| Address | 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. China |
| Bibliography | Journal of Microbiology, 57(1),64–73, 2019, |
| DOI | 10.1007/s12275-019-8416-0 |
| Key Words | Salmonella Typhimurium, phosphotransferase system, live attenuation vaccine |
| 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. |