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“Superbugs”
MRSA or Methicillin Resistant Staphyloccocus aureus
What is MRSA?
A common bacterium that can causes infections in different parts of the body.
Usually no problem but it has become resistant to some commonly used antibiotics.
Staphylococcus aureus - a short history

Bacteria have very good adaptive capabilities

1940s: Penicillin was introduced - a strong selective pressure, induces mutation

Bacteria can transfer traits by plasmids such as heavy metal tolerance etc

Penicillin was virtually useless as an antibiotic within a decade because a
plasmid spread the penicillinase (ß-lactamase) gene through the entire species
of S. aureus.

New antibiotics such as methicillin which were not degraded by the product of
the penicillinase gene were used

By 1960 methicillin resistant S. aureus (MRSA) strains were identified

By the 1980s, epidemic clones of MRSA acquired multidrug resistant traits and
spread worldwide to become one of the most important causes of hospital
acquired infections

In the early 2000s, MRSA strains carrying the Tn1546 transposon-based
enterococcal vancomycin resistant mechanism were identified in clinical
specimens, bringing the possibility of a totally resistant bacterial pathogen
closer to reality
How did this happen?

Selection pressure applied

S. aureus acquired a mutated gene :
o the penicillinase gene (via a plasmid)
o then the methicillin resistance gene mec
Mec:

Originated in S. scuiri another species of Staphylococcus

Located in a mobile piece of DNA that contains its own enzymes for moving it
around the genome

This piece of DNA is called the Staphylococcal cassette chromosome mec
(SCCmec)

Has about 100 ORF on this element – so also contains other genes genes
Mobile DNA

Common in bacteria
Two general types:
1. Plasmids

extrachromosomal circular or linear DNA molecules which are not part of
the bacterial genome

carry functions advantageous to the host such as eg antibiotics or heavy
metal resistance
2. Transposons

jumping genes, mobile genetic elements

composed of a gene coding for a special enzyme and two short flanking
segments of DNA called inverted repeats
How do antibiotics work?
Penicillin (β-lactam)
• Inhibits formation of peptidoglycan cross-links in the bacterial cell wall,
normally done by PBPs (penicillin binding proteins or transpeptidases )
• The β-lactam moiety (functional group) of penicillin binds to the enzyme
(PBPs)
– weakens the cell wall of the bacterium and causes lysis
Resistance to Penicillin
• Bacteria evolved Penicillinases which hydrolysing penicillin
Methicillin (also β-lactam)
• Acts the same way as Penicillin
• BUT insensitive to penicillinases
Resistance to Methicillin
• Expresses a different PBP, called PBP2a, that is resistant to methicillin
• Often resistant S. aureus are resistant to other classes of antibiotics (through
different mechanisms)
• Accessory factors (genes) influence the level and nature of methicillin
resistance
Key concepts

Plasmids - mobile genetic elements

Bacterial conjugation

Selection pressure - single drug, single mode of action, high numbers of
progeny, transferable DNA elements

Mutation - plasmids and transposons