ABSTRACT
Introduction ........................................................................................................ 292 Emergence of MRSA ......................................................................................... 292 Molecular Basis for Methicillin Resistance ....................................................... 293
Mechanisms of Resistance to Methicillin .............................................. 293 SCCmec .................................................................................................. 293
mecA .......................................................................................... 295 PBP2a .......................................................................................... 295 Regulation of mecA ...................................................................... 295
Chromosomal Elements Affecting Methicillin Resistance Levels ........ 296 Heterogeneous Methicillin Resistance ................................................... 298 Origins of Methicillin Resistance ........................................................... 299
Epidemiology of MRSA .................................................................................... 300 Nosocomial Infections ............................................................................ 300 Community-Acquired MRSA ................................................................. 301 Cost Attributable to MRSA .................................................................... 302
Expectations for the Future ................................................................................ 303 References .......................................................................................................... 304
Before the advent of antibiotic therapy, invasive staphylococcal infection was often fatal. The bacterium Staphylococcus aureus has since demonstrated a remarkable ability to adapt to antibiotic pressure. Methicillin-resistant strains of S. aureus, termed MRSA, are those strains that have acquired the ability to grow in the presence of methylpenicillins and derivatives, including methicillin, oxacillin, and nafcillin. This methicillin resistance is mediated by the acquisition and expression of an altered penicillin-binding protein, PBP2a (PBP2′), which exhibits a decreased af nity for β-lactam antibiotics [1,2]. Penicillin-binding proteins (PBPs) are essential enzymes that catalyze transpeptidation crosslinking of peptidoglycan in the bacterial cell wall and are the targets of the antibiotic methicillin in sensitive strains of S. aureus. Inhibition of this reaction with methicillin results in the arrest of cell wall biosynthesis,
triggering death of the organism through induction of the autolytic response [3]. MRSA possess a 21-to 67-kb DNA sequence that encodes, among other things, PBP2a and genes for regulation of its expression. Methicillin-susceptible strains are inhibited by oxacillin at concentrations of 4 μg/mL or methicillin at 8 μg/mL. In contrast, MRSA grow in the presence of 16 μg/mL to over 2000 μg/mL of methicillin.
