Aminoglycoside antibiotics induce bacterial biofilm formation¹

Nature ,vol 436, 1171~1175, 2005

Speaker: 李璟采

Date: 2005/10/26 14:00~15:00

Place:Room 601

Commentator: 劉清泉 醫師

Abstract:

Biofilm is produced by Pseudomonas aeruginosa, which causes serious lung infections in patients with cystic fibrosis. The authors have shown that subinhibitory concentration of aminoglycosides, such as tobramycin, induced biofilm formation in P. aeruginosa ². They found that tobramycin-induced biofilm formation of algD mutant, which is defective in alginate production was equivalent to that of wild type strain. This suggests that tobramycin-induced biofilm formation was not due to the increase of extracellular matrix. They also detected the same response in E. coli that was isolated from patients with bacteraemia. Based on a previous study, the second messenger, c-di-GMP, regulates cell adhesiveness in a diverse range of bacteria³. There are 38 genes that are predicted to encode a regulator which controls intracellular c-di-GMP levels. They found that the arrgene was involved in the signaling pathway of tobramycin- induced biofilm formation. The EAL domain (putative phosphodiesterases for c-di-GMP degradation) encoded by arrshowed phosphodiesterase activity, and could inactivate c-di-GMP and augment biofilm formation while the bacterium was treated with tobramycin. They then isolated two mutants of PAO1, filC and pilA, which encode bacterial surface appendages such as flagella and pili. They found that the biofilm formation of these two mutants are similar to that of wild type strain, suggesting that the induction of biofilm was not facilitated by surface appendages. In contrast, they found that biofilm formation was decreased when arr was mutated. Therefore, the tobramycin-induced biofilm formation was affected by the integrity of arr. Since the biofilm can reduce the function of antibiotics, we can manipulate the c-di-GMP metabolism to increase bacterial susceptibility to standard therapy.

References:

1.  Hoffman L. R., et al. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature, 436, 1171~1175, 2005 .

2.      Goodman, L. S. & Gilman, A. The pharmacological basis of therapeutics. Macmillan, New York, 2001 pp.1219~1238

3.      Simm, R., Morr, M., Kader, A., Nimtz, M. & Romling, U. GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol. Microbiol. 53, 1123–-1134 (2004).