Molecular Mechanisms of Biofilm Infection: Biofilm Virulence Factors.

BACKGROUND: Numerous planktonic virulence factors have been identified that enable bacteria to successfully produce acute infections in tissues. In contrast, very little is known about biofilm virulence factors that enhance the establishment and long-term survival of biofilms in tissues. THE PROBLEM: There is a need to identify the genes that encode biofilm virulence factors and understand how these factors function to enable bacteria to successfully establish chronic biofilm infections in tissues. BASIC SCIENCE ADVANCES: A methodology was developed to screen 6,912 Pseudomonas aeruginosa loss-of-function mutants in a murine model of airway infection to determine which genes were crucial for establishing chronic lung infections in mice. Genetic analysis of 16 bacterial mutants isolated using this methodology identified 15 separate biofilm virulence factor genes whose loss-of-function increased biofilm survival. Sequence analysis of clinical Isolates obtained from seven cystic fibrosis (CF) patients with chronic infections that were collected over 16.3 years identified loss-of-function mutants for 7 of these 15 genes. CLINICAL CARE RELEVANCE: Identifying biofilm virulence factor genes further defines the molecular mechanisms of establishing chronic biofilm infection and should lead to more effective and specific treatments to prevent biofilm formation and/or improve clearance of chronic biofilms in patients.
CONCLUSION: Biofilm virulence factor genes were identified in P. aeruginosa using an animal model of chronic lung infection for mutant screening and from infected CF patient isolates. In many cases they were inactivated planktonic virulence factor genes. These results further demonstrate the opposing patterns of gene expression between acute planktonic bacterial infections and chronic biofilm infections.