Genetic basis of resistance to fusidic acid in staphylococci

Abstract

Resistance to fusidic acid in Staphylococcus aureus often results from acquisition of the fusB determinant or from mutations in the gene (fusA) that encodes the drug target (elongation factor G). We now report further studies on the genetic basis of resistance to this antibiotic in the staphylococci. Two staphylococcal genes that encode proteins exhibiting ca. 45% identity with FusB conferred resistance to fusidic acid in S. aureus. One of these genes (designated fusC) was subsequently detected in all fusidic acid-resistant clinical strains of S. aureus tested that did not carry fusB or mutations in fusA, and in strains of S. intermedius. The other gene (designated fusD) is carried by S. saprophyticus, explaining the inherent resistance of this species to fusidic acid. Fusidic acid-resistant strains of S. lugdunensis harbored fusB. Thus, resistance to fusidic acid in clinical isolates of S. aureus and other staphylococcal species frequently results from expression of FusB-type proteins.

FIG. 1.

Protein alignment between FusB, YP_042173 (FusC from S. aureus MSSA476), and YP_302255 (FusD from S. saprophyticus ATCC 15305). Gray shading indicates identity in two sequences; black shading indicates identity in all three sequences.

FIG. 2.

Detection of fusB and fusC in staphylococci. (A) Detection of fusC by Southern hybridization in a representative set of fusidic acid-resistant clinical strains of S. aureus that harbor neither fusB nor resistance polymorphisms in fusA. MSSA476 is the positive control. (B) Detection of fusB by Southern hybridization in clinical strains of S. lugdunensis. pUB101 is the positive control, while S. aureus 74136 is an EEFIC strain (see the text). (C) PCR analysis maps fusB downstream of groEL in S. lugdunensis 16641 and 16496, the same location as that in EEFIC strain, S. aureus 74136. The other three strains are negative controls.