Methicillin-Resistant Staphylococcus Aureus

Staphylococcus aureus (S. aureus) are gram-positive cocci-shaped bacteria that are commonly found throughout the environment, including on the skin of healthy individuals. S. aureus is essentially benign on the skin, although if allowed to enter the bloodstream or internal tissues, S. aureus can cause a range of potentially serious infections. A person who has had some sort of skin trauma (including a minor cut) may be susceptible to a variety of different skin and soft-tissue infections caused by S. aureus, but the infection can usually be successfully treated with penicillin-derived antibiotics. MRSA, or methicillin-resistant S. aureus, are bacteria that have become highly resistant to many commonly used antibiotics, such as methicillin. MRSA infections are more difficult to treat because traditional antibiotics are ineffective, and patients must therefore be treated with alternative antibiotics. Until the 1990s, identified cases of MRSA were confined primarily to hospitals and healthcare facilities, although MRSA can now be found [Page 295]worldwide in community settings. MRSA infections can range in severity from minor to very serious and even fatal. In 2005, it was estimated that about 20 percent of those MRSA infections categorized as “serious” resulted in the death of the patient. As a result, MRSA have emerged as very serious nosocomial (hospital-acquired) and community-acquired pathogens.

Methicillin is a semi-synthetic beta-lactamase-resistant penicillin antibiotic that was introduced in 1959 to aid in the fight against bacterial infection. Remarkably, S. aureus strains resistant to methicillin were reported soon after the introduction of this antibiotic. In the early 1960s, outbreaks of MRSA infections were reported in Europe. Since then, scientists around the globe have identified different strains of MRSA and, using genetic testing, three of those can be traced back to the original MRSA strains first isolated in Europe in the 1960s.

All known S. aureus strains that are resistant to methicillin (MRSA strains) carry a gene known as mec on the bacterial chromosome. Strains of S. aureus that do not have the mec gene are sensitive to methicillin and are therefore termed methicillin-sensitive S. aureus (MSSA). The mec gene is a component of the larger Staphylococcal chromosomal cassette mec (SCCmec). To date, at least six different SCCmec types have been identified (types I-VI). The mec gene encodes a penicillin-binding protein 2a (PBP-2a), which ultimately gives mec-carrying microorganisms resistance to methicillin and many other beta-lactam antibiotics such as nafcillin, oxacillin, and cephalosporins. Penicillin-binding proteins (PBPs) are essential protein enzymes in the bacterial cell wall that catalyze the production of an important structural barrier of the cell wall known as peptidoglycan. As their name suggests, some PBPs also bind to penicillin-derived antibiotics (beta-lactams), which results in inactivation of the PBP enzyme activity and ultimately death of the bacterial cell. The protein encoded by the mec gene, PBP-2a, has a low affinity for beta-lactams and therefore, even in the presence of most antibiotics, PBP-2a will continue to catalyze the synthesis of the bacterial cell wall. This continued function of PBP-2a in the presence of antibiotics such as methicillin results in growth and survival of MRSA strains even in the presence of prolonged antibiotic treatment.

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