PMID- 33315153 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201217 IS - 2191-0855 (Print) IS - 2191-0855 (Electronic) IS - 2191-0855 (Linking) VI - 10 IP - 1 DP - 2020 Dec 14 TI - Oral administration of recombinant Bacillus subtilis spores expressing mutant staphylococcal enterotoxin B provides potent protection against lethal enterotoxin challenge. PG - 215 LID - 10.1186/s13568-020-01152-x [doi] LID - 215 AB - Pathogenicity of Staphylococcus aureus is induced by staphylococcal enterotoxin B (SEB). A mutant form of SEB (mSEB) is immunogenic as well as less toxic. Recombinant mSEB and SEB were expressed in pET28a prokaryotic plasmids. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in mSEB-stimulated macrophages were lower than those in SEB-stimulated macrophages (p < 0.001, p < 0.01 respectively). Using CotC as a fusion protein, we constructed recombinant Bacillus subtilis spores expressing mSEB on the spore surface and evaluated their safety and protective efficacy via mouse models. Oral administration of mSEB-expressing spores increased SEB-specific IgA in feces and SEB-specific IgG1 and IgG2a in the sera, compared with mice in naive and CotC spore-treated groups (p < 0.001, p < 0.01, p < 0.001 respectively). Six weeks following oral dosing of recombinant spores, significant differences were not found in the serum biochemical indices between the mSEB group and the naive and CotC groups. Furthermore, oral administration of mSEB spores increased the survival rate by 33.3% in mice intraperitoneally injected with 5 microg of wild-type SEB plus 25 microg lipopolysaccharide (LPS). In summation, recombinant spores stably expressing mSEB were developed, and oral administration of such recombinant spores induced a humoral immune response and provided protection against SEB challenge in mice. FAU - Xiong, Zhile AU - Xiong Z AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Mai, Jialiang AU - Mai J AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Li, Fei AU - Li F AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Liang, Bingshao AU - Liang B AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Yao, Shuwen AU - Yao S AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Liang, Zhuwei AU - Liang Z AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Zhang, Chao AU - Zhang C AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Gao, Fei AU - Gao F AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Ai, Xiaolan AU - Ai X AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Wang, Jielin AU - Wang J AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Long, Yan AU - Long Y AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Yang, Min AU - Yang M AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Gong, Sitang AU - Gong S AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. FAU - Zhou, Zhenwen AU - Zhou Z AD - Clinical laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China. zzw6248@126.com. LA - eng GR - 30801054/National Natural Science Foundation of China/ GR - no.2016A020215013 and no. 2014A020212013/the Guangdong Science and Technology Foundation/ GR - No. 201102A212013, No. 20131A011053, and No. 20171A010267/the Medical Health Science and Technology Foundation of Guangzhou/ GR - No. 201707010010/Science and Technology Foundation of Guangzhou/ GR - No. 20181A011039/Guangzhou Health and Family Planning Science and Technology Project/ GR - No. 8451012001001570 and No. 915101200F009/the Natural Science Foundation of Guangdong/ GR - Nos. Pre-NSFC-2019-014 and IP-2019-022/Paediatric Institute Foundation of Guangzhou Women and Children's Medical Center/ PT - Journal Article DEP - 20201214 PL - Germany TA - AMB Express JT - AMB Express JID - 101561785 PMC - PMC7734462 OTO - NOTNLM OT - Bacillus subtilis OT - Staphylococcal enterotoxin B OT - Staphylococcus aureus OT - Vaccination COIS- The authors all declare that they have no competing interests. EDAT- 2020/12/15 06:00 MHDA- 2020/12/15 06:01 PMCR- 2020/12/14 CRDT- 2020/12/14 12:09 PHST- 2020/09/20 00:00 [received] PHST- 2020/11/25 00:00 [accepted] PHST- 2020/12/14 12:09 [entrez] PHST- 2020/12/15 06:00 [pubmed] PHST- 2020/12/15 06:01 [medline] PHST- 2020/12/14 00:00 [pmc-release] AID - 10.1186/s13568-020-01152-x [pii] AID - 1152 [pii] AID - 10.1186/s13568-020-01152-x [doi] PST - epublish SO - AMB Express. 2020 Dec 14;10(1):215. doi: 10.1186/s13568-020-01152-x.