Growth inhibition of multiresistant enterococci by interferon-gamma-activated human uro-epithelial cells

Nosocomial infections with enterococci are an increasing problem in modern medical practice due to the development of resistance to a wide range of an tibiotics, including the glycopeptides vancomycin and teicoplanin, An incre asing number of vancomycin-resistant enterococci (VRE) have been cultured f rom clinical specimens - especially from patients undergoing immunosuppress ive therapy - and bacteraemia caused by these VRE, subsequent to colonisati on of epithelial surfaces, is a significant cause of mortality in such pati ents, Recent evidence showed that the induction of indoleamine 2,3 dioxygen ase (IDO) by interferon-gamma (IFN-gamma) inhibited growth of group B strep tococci by depleting the essential amino acid L-tryptophan, This study desc ribes the IFN-gamma-induced expression of IDO - shown at a transcriptional level by Northern blot analysis, at translational level by Western blot and also at a functional level by L-tryptophan degradation to L-kynurenine - i n the uro-epithelial cell line RT4, The depletion of L-tryptophan resulted in growth inhibition of enterococci, and this was confirmed by abrogation o f the inhibitory effect by re-supplementation with excess L-tryptophan, Mul tiresistant enterococci, including vancomycin-resistant strains resistant t o all commercially available antibiotics, were inhibited by the IFN-gamma-i nduced expression of IDO and subsequent L-tryptophan degradation, This may be an important mechanism in the local restriction of colonisation of the u rinary tract by endogenous enterococci and in inhibiting the spread of the bacteria beyond the epithelial barrier.