Proteomic Adaptation of <i>Clostridioides difficile</i> to Treatment with the Antimicrobial Peptide Nisin

• Published in: Cells
• Main Authors: Sandra Maaß, Jürgen Bartel, Pierre-Alexander Mücke, Rabea Schlüter, Thomas Sura, Julia Zaschke-Kriesche, Sander H. J. Smits, Dörte Becher
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Subjects: nisin; antimicrobial peptides; antibiotic resistance; mass spectrometry; <i>C. difficile</i>; proteomics
• Online Access: https://www.mdpi.com/2073-4409/10/2/372

<i>Clostridioides difficile</i> is the leading cause of antibiotic-associated diarrhea but can also result in more serious, life-threatening conditions. The incidence of <i>C. difficile</i> infections in hospitals is increasing, both in frequency and severity, and antibiotic-resistant <i>C. difficile</i> strains are advancing. Against this background antimicrobial peptides (AMPs) are an interesting alternative to classic antibiotics. Information on the effects of AMPs on <i>C. difficile</i> will not only enhance the knowledge for possible biomedical application but may also provide insights into mechanisms of <i>C. difficile</i> to adapt or counteract AMPs. This study applies state-of-the-art mass spectrometry methods to quantitatively investigate the proteomic response of <i>C. difficile</i> 630∆<i>erm</i> 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.