title: Novel therapeutic strategies for Clostridium difficile infections.
abstract: BACKGROUND
  In recent years, Clostridium difficile has become the primary cause of antibiotic-associated diarrhea and pseudomembranous colitis, resulting in long and complicated hospital stays that represent a serious burden for patients as well as health care systems. Currently, conservative treatment of C. difficile infection (CDI) relies on the antibiotics vancomycin, metronidazole or fidaxomicin, or in case of multiple recurrences, fecal microbiota transplantation (FMT).
  
  
  METHODS
  The fast-spreading, epidemic nature of this pathogen urgently necessitates the search for alternative treatment strategies as well as antibiotic targets. Accordingly, in this review, we highlight the recent findings regarding virulence associated traits of C. difficile, evaluate their potential as alternative drug targets, and present current efforts in designing inhibitory compounds, with the aim of pointing out possibilities for future treatment strategies.
  
  
  CONCLUSIONS
  Increased attention on systematic analysis of the virulence mechanisms of C. difficile has already led to the identification of several alternative drug targets. In the future, applying state of the art 'omics' and the development of novel infection models that mimic the human gut, a highly complex ecological niche, will unveil the genomic and metabolic plasticity of this pathogen and will certainly help dealing with future challenges.
authors.affiliation: a 1 Technische Universität Braunschweig, Institut für Mikrobiologie , Spielmannstr. 7, D-38106, Braunschweig, Germany ; m.steinert@tu-bs.de.|b 2 Türk-Alman Üniversitesi, Fen Fakültesi , Şahinkaya Cad. 86, 34820, Istanbul, Turkey.
authors.forename: Can M
authors.initials: CM
authors.lastname: Ünal
authors.affiliation: a 1 Technische Universität Braunschweig, Institut für Mikrobiologie , Spielmannstr. 7, D-38106, Braunschweig, Germany ; m.steinert@tu-bs.de.|c 3 Helmholtz Centre for Infection Research , Mascheroder Weg 1, 38124, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Steinert
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology; D015195:Drug Design; D006760:Hospitalization; D006801:Humans; D007902:Length of Stay
chemical_list: D000900:Anti-Bacterial Agents
keywords: C. difficile infection; CDAD; Clostridium difficile; alternative drug targets; antibiotic resistance; small inhibitors; therapeutics; toxins; virulence factors