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Vaccine · 2026

Oral delivery of recombinant Bacillus subtilis expressing mSEB reduces intestinal Staphylococcus aureus colonization.

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Yang Kaiyue, He Yunxing, Zhou Xiaojie, Ding Tongyan, Liu Shuyan, Lin Shaoxiang, Liu Xiaochun, Zhou Zhenwen

Аннотация

BACKGROUND: S. aureus intestinal colonization elevates infection risk, underscoring decolonization as a key prevention target. SEB is a key target for the development of neutralizing antibodies against toxins to prevent and treat S. aureus infection. B. subtilis is used as a probiotic for human health.

OBJECTIVE: To investigate the efficacy of recombinant mSEB B. subtilis spores for reducing S. aureus intestinal colonization in mouse.

METHODS: Mice were orally immunized with recombinant mSEB spores three times a week for three weeks. After immunization, mice were challenged via oral gavage with 1 × 109 CFU of S. aureus (ATCC 14458). Fecal specific IgA and serum IgG1 and IgG2a were analyzed by ELISA. Peritoneal macrophages were isolated for qRT-PCR analysis of TNF-α, IL-6 and IL-1β mRNA expression. Colon contents samples underwent 16S rRNA sequencing for microbiota profiling. Intestinal RNA was extracted for transcriptome sequencing (RNA-seq), and differential pathways were analyzed using KEGG enrichment. Body weight and fecal viable S. aureus burden were monitored.

RESULTS: Oral mSEB spores correlated with elevated systemic and mucosal SEB-specific IgG1, IgG2a and fecal sIgA (P < 0.01). After S. aureus challenge, peritoneal macrophages from mSEB mice showed lower pro-inflammatory TNF-α, IL-6 and IL-1β transcripts, consistent with attenuated systemic inflammation. mSEB immunization also altered gut microbiota and increased the relative abundance of Barnesiella. Intestinal RNA-seq identified enriched antigen presentation and B cell receptor signaling gene sets in the mSEB group. On day 3 post-challenge, fecal S. aureus loads were 24.20 ± 3.967 × 104 CFU (Control), 8.081 ± 3.614 × 104 CFU (CotC) and 3.6 ± 1.030 × 104 CFU (mSEB), showing a pathogen-clearing phenotype linked to mSEB treatment.

CONCLUSION: Immunization with mSEB-displaying Bacillus subtilis spores correlates with SEB-specific mucosal and systemic antibody responses, blunted systemic inflammation, modified gut microbiota, and reduced intestinal S. aureus burdens post-challenge. The causal mechanisms underlying these changes remain to be clarified.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты