Staphylococcal resistance to penicillin is mediated by penicillinase (a form of beta-lactamase) production: an enzyme that cleaves the β-lactam ring of the penicillin molecule, rendering the antibiotic ineffective.
Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation by staphylococcal penicillinase.

Resistance to methicillin is mediated via the mec operon, part of the staphylococcal cassette chromosome mec (SCCmec).
SCCmec is a family of mobile genetic elements, which is a major driving force of S. aureus evolution.
Resistance is conferred by the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems).
This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections.
Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains.

Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit.
Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria.

Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic.
 This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity.
 In S. aureus, the best-characterized aminoglycoside-modifying enzyme is aminoglycoside adenylyltransferase 4' IA (ANT(4')IA).
 This enzyme has been solved by X-ray crystallography.
The enzyme is able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kamamycin and gentamicin.

Glycopeptide resistance is mediated by acquisition of the vanA gene, which originates from the Tn1546 transposon found in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.

Today, S. aureus has become resistant to many commonly used antibiotics.
 In the UK, only 2% of all S. aureus isolates are sensitive to penicillin, with a similar picture in the rest of the world.
The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S. aureus, and are still used as first-line treatment.
 Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but, only two years later, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was reported in England.

Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it is now endemic.

MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole).
 Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug.
First-line treatment for serious invasive infections due to MRSA is currently glycopeptide antibiotics (vancomycin and teicoplanin).
 A number of problems with these antibiotics occur, such as the need for intravenous administration (no oral preparation is available), toxicity, and the need to monitor drug levels regularly by blo
Staphylococcal resistance to penicillin is mediated by penicillinase (a form of beta-lactamase) production: an enzyme that cleaves the β-lactam ring of the penicillin molecule, rendering the antibiotic ineffective. Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation by staphylococcal penicillinase.
Resistance to methicillin is mediated via the mec operon, part of the staphylococcal cassette chromosome mec (SCCmec). SCCmec is a family of mobile genetic elements, which is a major driving force of S. aureus evolution. Resistance is conferred by the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems). This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections. Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains.
Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit. Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria.
Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic.  This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity.  In S. aureus, the best-characterized aminoglycoside-modifying enzyme is aminoglycoside adenylyltransferase 4' IA (ANT(4')IA).  This enzyme has been solved by X-ray crystallography. The enzyme is able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kamamycin and gentamicin.
Glycopeptide resistance is mediated by acquisition of the vanA gene, which originates from the Tn1546 transposon found in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.
Today, S. aureus has become resistant to many commonly used antibiotics.  In the UK, only 2% of all S. aureus isolates are sensitive to penicillin, with a similar picture in the rest of the world. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S. aureus, and are still used as first-line treatment.  Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but, only two years later, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was reported in England.
Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it is now endemic.
MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole).  Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA is currently glycopeptide antibiotics (vancomycin and teicoplanin).  A number of problems with these antibiotics occur, such as the need for intravenous administration (no oral preparation is available), toxicity, and the need to monitor drug levels regularly by blo
Staphylococcus aureus