Subtractive Hybridization Yields a Silver Resistance Determinant Unique to Nosocomial Pathogens in the Enterobacter cloacae Complex

The heterogeneity and the increasing clinical importance of the Enterobacter cloacae complex have often been discussed. However, little is known about molecular factors causing pathogenicity within this nomenspecies. Here, we analyzed the genetic differences between an avirulent plant isolate and a pathogenic strain causing an outbreak with septicemia in three patients. We identified an IncHI-2 plasmid as a major difference between these two strains. Besides resistance to several antibiotics, this plasmid encoded a silver resistance determinant. We further showed that this sil determinant was present not only in the analyzed outbreak strain but also in the vast majority of clinical isolates of the E. cloacae complex, predominantly in (sub)species that frequently cause nosocomial infections. The identified sil determinant was highly conserved within the E. cloacae complex and mediated resistance to up to 600 mu M silver nitrate. As silver is often used as a disinfectant and treatment for burn wounds, we present here an important fitness factor within the clinically most prevalent subspecies of the E. cloacae complex. This provides a possible explanation for their unequal involvement in nosocomial and especially burn wound infections.