Proteomic Adaptation of Clostridioides difficile to Treatment with the Antimicrobial Peptide Nisin

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea but can also result in more serious, life-threatening conditions. The incidence of C. difficile infections in hospitals is increasing, both in frequency and severity, and antibiotic-resistant C. difficile strains are advancing. Against this background antimicrobial peptides (AMPs) are an interesting alternative to classic antibiotics. Information on the effects of AMPs on C. difficile will not only enhance the knowledge for possible biomedical application but may also provide insights into mechanisms of C. difficile to adapt or counteract AMPs. This study applies state-of-the-art mass spectrometry methods to quantitatively investigate the proteomic response of C. difficile 630 increment erm to sublethal concentrations of the AMP nisin allowing to follow the cellular stress adaptation in a time-resolved manner. The results do not only point at a heavy reorganization of the cellular envelope but also resulted in pronounced changes in central cellular processes such as carbohydrate metabolism. Further, the number of flagella per cell was increased during the adaptation process. The potential involvement of flagella in nisin adaptation was supported by a more resistant phenotype exhibited by a non-motile but hyper-flagellated mutant.

Automated summary

Clostridioides difficile is increasingly causing infections in hospitals, with antibiotic-resistant strains becoming more common. Research on the effects of antimicrobial peptides on C. difficile can provide valuable insights for biomedical applications and understanding the mechanisms of adaptation or resistance. Advanced mass spectrometry methods were used to study the proteomic response of C. difficile to sublethal concentrations of the AMP nisin, revealing significant changes in cellular processes and potential involvement of flagella in adaptation.