The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides

Abstract

Staphylococcus epidermidis is a normal constituent of the healthy human microflora, but it is also the most common cause of nosocomial infections associated with the use of indwelling medical devices. Isolates from device-associated infections are known for their pronounced phenotypic and genetic variability, and in this study we searched for factors that might contribute to this flexibility. We show that mutator phenotypes, which exhibit elevated spontaneous mutation rates, are rare among both pathogenic and commensal S. epidermidis strains. However, the study revealed that, in contrast to those of commensal strains, the genomes of clinical S. epidermidis strains carry multiple copies of the insertion sequence IS256, while other typical staphylococcal insertion sequences, such as IS257 and IS1272, are distributed equally among saprophytic and clinical isolates. Moreover, detection of IS256 was found to be associated with biofilm formation and the presence of the icaADBC operon as well as with gentamicin and oxacillin resistance in the clinical strains. The data suggest that IS256 is a characteristic element in the genome of multiresistant nosocomial S. epidermidis isolates that might be involved in the flexibility and adaptation of the genome in clinical isolates.

FIG. 1.

Distribution of IS256, IS257, and IS1272 among 230 S. epidermidis isolates from different origins. The study comprised 53 isolates recovered from blood cultures, 38 isolates obtained from catheter-related urinary tract infections, and 139 commensal strains obtained from nasal swabs of healthy volunteers.

FIG. 2.

Antibiotic resistance, biofilm formation, detection of the icaADBC operon, and IS256 presence in clinical and commensal S. epidermidis strains.

FIG. 3.

Scheme of Tn4001 and position of primers used for the detection of the transposon. (Please note that the image is not drawn to scale.)

FIG. 4.

Detection of multiple IS256 copies by IS256-specific Southern hybridization of EcoRI-digested chromosomal DNA of different gentamicin-resistant S. epidermidis strains (208 to 581). S. epidermidis RP62A and S. carnosus TM300 were used as positive and negative controls, respectively.

FIG. 5.

Spontaneous mutation frequencies per cell and generation of the commensal and clinical S. epidermidis strains toward rifampin resistance.