Linezolid Resistance in Staphylococcus aureus : Gene Dosage Effect, Stability, Fitness Costs, and Cross-Resistances

Abstract

Linezolid resistance in Staphylococcus aureus is typically associated with mutations in the 23S rRNA gene. Here we show that the accumulation of a single point mutation, G2576T, in the different copies of this gene causes stepwise increases in resistance, impairment of the biological fitness, and cross-resistance to quinupristin-dalfopristin and chloramphenicol.

Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

“…Cross-resistance to linezolid, chloramphenicol, and dalfopristin (the streptogramin A component of Synercid) is associated with the second shell nucleotide G2576U mutation (10). Linezolid, chloramphenicol, and streptogramin A bind at the PTC via the first shell nucleotide G2505, which is stacked to U2576.…”

“…Eubacteria possess several copies of rRNA operons; thus, acquisition of single-nucleotide mutations and/or posttranscription modifications in the 23S rRNA, which are among the common resistance mechanisms with respect to ribosomal antibiotics that enter the cells, should occur after relatively long periods (10). Nevertheless, the epidemiology of S. aureus is increasing (11).…”

Resistencia a antibióticos de última línea en cocos Gram positivos: la era posterior a la vancomicina

“…Estas mutaciones pueden presentarse en una, algunas o todas las copias de los genes que codifican el ARNr bacteriano y se ha observado una correlación directa entre el número de copias mutadas y el nivel de resistencia al linezolid (53). Cabe destacar que las mutaciones en los genes que codifican para los ARNr parecen afectar la viabilidad bacteriana (bacterial fitness), observándose una relación inversa entre el número de copias mutadas y la capacidad de crecimiento de la bacteria (53). La aparición de este mecanismo de resistencia in vivo se ha asociado con prolongados esquemas de tratamiento con linezolid y con su amplio uso en instituciones hospitalarias (54,55).…”

Biological activities of pargamicin A, a novel cyclic peptide antibiotic from Amycolatopsis sp.

“…4 Although these drugs have been recently launched, drug-resistant strains against these drugs have already been clinically isolated. [5][6][7][8][9][10][11] In the course of our screening program for new antibiotics, which are active against both MRSA and VRE, pargamicin A (PRGA) as shown in Figure 1, was isolated from the soil actinomycete strain Amycolatopsis sp. ML1-hF4.…”