Spontaneous Deletion of the Methicillin Resistance Determinant, mecA , Partially Compensates for the Fitness Cost Associated with High-Level Vancomycin Resistance in Staphylococcus aureus

Abstract

Treatment of infections caused byStaphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.

Offsetting virulence and antibiotic resistance costs by MRSA

“…Previous studies have shown that the relative fitness of hospital-acquired MRSAs carrying the type I SCCmec element is reduced (Ender et al, 2004), whereas strains containing the smaller type IV element were not affected (Lee et al, 2007). It has also been shown in vancomycin-resistant MRSA strains containing the type II SCCmec element that deletion of mecA compensated for some of the fitness costs associated with becoming vancomycin resistant, suggesting that mecA is also costly (Noto et al, 2008). A detailed study of the costs associated with all five classes of SCCmec elements and whether these costs have been compensated in clinical strains has not been performed to date.…”

Genotypic relatedness and characterization of Staphylococcus pseudintermedius associated with post-operative surgical infections in dogs

“…This observation suggests a fitness cost that may be associated with the presence of the mecA gene. A similar observation has been made in studies on S. aureus, where isolates lacking the mecA gene are able to outcompete their mecA-containing counterparts (Noto et al, 2008). However, this observation was made on only a single strain and therefore needs to be confirmed using a panel of similar strains.…”

Epidemiological and molecular biological studies of multi-resistant methicillin-susceptible Staphylococcus aureus

“…Spontaneous excision of mecA, causing MSSA to emerge from MRSA both in vivo and in vitro, has been described in several other studies [138][139][140]. This phenomenon may be due to stressful conditions in vitro, such as long-term storage in antibiotic-free medium, nutrient starvation, elevated temperatures or UV radiation [138,[141][142].…”

“…This phenomenon may be due to stressful conditions in vitro, such as long-term storage in antibiotic-free medium, nutrient starvation, elevated temperatures or UV radiation [138,[141][142]. Furthermore, prolonged therapy with non-β-lactam antibiotics and exposure to vancomycin can be contributing factors, resulting in partial excision of SCCmec [140].…”