Pathogenesis of human-derived Bacillus cereus strains: lessons from the insect Galleria mellonella immune responses

人源蜡样芽孢杆菌菌株的致病性:来自大蜡螟免疫反应的启示

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Abstract

INTRODUCTION: Bacillus cereus is responsible for a wide range of intestinal and extraintestinal infections in humans. Its pathogenicity relies on multiple factors, including extracellular toxins, direct interaction with host tissues, and adaptive mechanisms that promote host colonization. B. cereus group bacteria are also insect pathogens (e.g., Bacillus thuringiensis), suggesting that certain virulence mechanisms may be conserved between mammals and insects. METHODS: In this study, we used Galleria mellonella as an infection model to assess the pathogenicity of two B. cereus strains (i.e., T1 and B10502), which were previously isolated from food poisoning outbreaks and that differ in their virulence toward human enterocyte cell cultures. We combined genomic analysis with larval infection assays to examine survival, bacterial persistence, immune activation, and spore formation. RESULTS: Whole-genome phylogenetic analysis revealed that the two strains belong to distinct branches of the B. cereus sensu lato species. Both strains induced dose-dependent mortality following oral gavage, with strain T1 showing a better persistence than strain B10502 in both living and dead larvae, with heat-resistant spores detectable up to 144 h post-infection, unlike strain B10502. Infection with strain B10502 elicited higher phenoloxidase activity and greater melanization than with strain T1. Both strains similarly reduced hemocyte viability. DISCUSSION/CONCLUSION: Genomic comparisons revealed that both strains share a core set of virulence factors, including the non-hemolytic enterotoxin (Nhe) complex, various hemolysins, and phospholipases, while exhibiting significant differences in genes, such as hblABCD complex, mpbE, clpC, clpP, and ilsA. These findings demonstrate that G. mellonella is a useful infection model to discriminate B. cereus strains with different virulence biological activities on larval colonization and innate immune markers, providing new insights into the mechanisms underlying the pathogenicity of foodborne B. cereus strains.

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