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Does antibiotic treatment increase bacterial virulence in cystic fibrosis?
  1. A de-Soyza
  1. Newcastle upon Tyne, UK; anthony.de-soyzancl.ac.uk

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Biofilm formation is an important bacterial protective mechanism that appears in the environment and clinical practice. The cystic fibrosis (CF) lung is a common model used to investigate biofilms. Recent data suggest that treatments used in CF may in part contribute to the phenotype.

This study reports that very low concentrations of aminoglycosides (including tobramycin, amikacin and streptomycin) induce biofilm formation in Pseudomonas strains, with tobramycin the most active. Thirteen of 14 CF isolates tested formed tobramycin induced biofilms at low concentrations of this antibiotic. Biofilms were not induced by the cationic antimicrobial peptide polymyxin B, although polymyxin E (colistin) was not assessed. The induction of biofilm was not dependent on the presence of bacterial outer membrane properties such as flagellin, pili, or the alginate gene responsible for “mucoidy”.

A transposon induced bank of mutant Pseudomonas strains allowed the identification of the gene responsible for tobramycin induced biofilms. The arr gene (aminoglycoside response regulator) was found to be conserved and had cyclic di-GMP (c-di-GMP) phosphodiesterase activity. Exogenous GTP (a c-di-GMP antagonist) inhibited aminoglycoside induced biofilm formation. Notably, biofilms of arr mutants were 100 times more sensitive to tobramycin in vitro. Given recent data that nebulised aminoglycoside treatment in the short term improves lung function, these new findings need to be interpreted with caution. The availability of a number of PDE inhibitors including dipyridamole and sildenafil have yet to be tested against the arr gene product and may offer a new therapeutic target.

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