Smith K, Gould KA, Ramage G, Gemmell CG, Hinds J, Lang S
The influence of tigecycline on the expression of virulence factors in biofilm-associated cells of methicillin resistant Staphylococcus aureus. [JOURNAL ARTICLE]
Antimicrob Agents Chemother 2009 Oct 26.
MRSA infections are complicated by the ability of the organism to grow in surface-adhered biofilms on a multitude of abiotic and biological surfaces. These multi-cellular communities are notoriously difficult to eradicate with antimicrobial therapy. Cells within the biofilm may be exposed to a sub-lethal concentration of the antimicrobial due to the metabolic and phenotypic diversity of biofilm-associated cells or the protection offered by the biofilm structure. In this study, the influence of a sub-lethal concentration of tigecycline on biofilms formed by an epidemic MRSA-16 isolate was investigated by transcriptome analysis. In the presence of the drug 309 genes were up-regulated and 213 genes were down-regulated by more than 2-fold in comparison to drug-free controls. Microarray data was validated by real-time RT-PCR and phenotypic assays. Tigecycline altered the expression of a number of genes encoding proteins considered to be crucial for the virulence of S. aureus. These included the reduced expression of icaC, involved in PIA production and biofilm development, the up-regulation of fnbA, clfB and cna, encoding adhesins which attach to human proteins and the down-regulation of the cap genes which mediate synthesis of the capsule polysaccharide. The expression of tst which encodes toxic shock syndrome toxin-1 (TSST-1), was also significantly reduced and an assay to quantify TSST-1 showed that toxin production decreased by 10-fold (P<0.001) in cells treated with tigecycline in comparison to un-treated controls. This study suggests that tigecycline may reduce the expression of important virulence factors in S. aureus and supports further investigation to determine whether it could be a useful adjunct to therapy for the treatment of biofilm-mediated infections.
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