Biofilm infections, their resilience to therapy and innovative treatment strategies

J Intern Med. 2012 Dec;272(6):541-61. doi: 10.1111/joim.12004. Epub 2012 Oct 29.


Biofilm formation of microorganisms causes persistent tissue and foreign body infections resistant to treatment with antimicrobial agents. Up to 80% of human bacterial infections are biofilm associated; such infections are most frequently caused by Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteria such as Escherichia coli. The accurate diagnosis of biofilm infections is often difficult, which prevents the appropriate choice of treatment. As biofilm infections significantly contribute to patient morbidity and substantial healthcare costs, novel strategies to treat these infections are urgently required. Nucleotide second messengers, c-di-GMP, (p)ppGpp and potentially c-di-AMP, are major regulators of biofilm formation and associated antibiotic tolerance. Consequently, different components of these signalling networks might be appropriate targets for antibiofilm therapy in combination with antibiotic treatment strategies. In addition, cyclic di-nucleotides are microbial-associated molecular patterns with an almost universal presence. Their conserved structures sensed by the eukaryotic host have a widespread effect on the immune system. Thus, cyclic di-nucleotides are also potential immunotherapeutic agents to treat antibiotic-resistant bacterial infections.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Infections* / drug therapy
  • Bacterial Infections* / microbiology
  • Bacterial Physiological Phenomena / drug effects
  • Biofilms* / classification
  • Biofilms* / drug effects
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Drug Resistance, Bacterial / physiology
  • Escherichia coli / physiology*
  • Humans
  • Pseudomonas aeruginosa / physiology*
  • Second Messenger Systems / physiology
  • Staphylococcus / physiology*
  • Therapies, Investigational / methods


  • Anti-Bacterial Agents
  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP