Clostridium difficilealters the structure and metabolism of distinct cecal microbiomes during initial infection to promote sustained colonization
AbstractSusceptibility toClostridium difficileinfection is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistentC. difficileinfection. As such, we utilized a mouse model of infection to explore the effect of distinct antibiotic classes on the impact that infection has on community-level transcription and metabolic signatures shortly following pathogen colonization and how those changes may associate with persistence ofC. difficile. Untargeted metabolomic analysis revealed thatC. difficileinfection had significantly larger impacts on the metabolic environment across cefoperazone and streptomycin-pretreated mice, which become persistently colonized compared to clindamycin-pretreated mice where infection quickly became undetectable. Through metagenome-enabled metatranscriptomics we observed that transcripts for genes associated with carbon and energy acquisition were greatly reduced in infected animals, suggesting those niches were instead occupied byC. difficile. Furthermore, the largest changes in transcription were seen in the least abundant species indicating thatC. difficilemay “attack the loser” in gut environments where sustained infection occurs more readily. Overall, our results suggest thatC. difficileis able to restructure the nutrient-niche landscape in the gut to promote persistent infection.