MECHANISM OF ACTION:

1. Drug inactivation or modification: for example, enzymatic deactivation

of penicillin G in some penicillin-resistant bacteria through the production of β-

lactamases. Drugs may also be chemically modified through the addition

of functional groups by transferase enzymes; for

example, acetylation, phosphorylation, or adenylation are common resistance

mechanisms to aminoglycosides. Acetylation is the most widely used mechanism

and can affect a number of drug classes.

2. Alteration of target- or binding site: for example, alteration of PBP—the binding

target site of penicillins—in MRSA and other penicillin-resistant bacteria. Another

protective mechanism found among bacterial species is ribosomal protection

proteins. These proteins protect the bacterial cell from antibiotics that target the

cell's ribosomes to inhibit protein synthesis. The mechanism involves the binding

of the ribosomal protection proteins to the ribosomes of the bacterial cell, which

in turn changes its conformational shape. This allows the ribosomes to continue

synthesizing proteins essential to the cell while preventing antibiotics from

binding to the ribosome to inhibit protein synthesis.

3. Alteration of metabolic pathway: for example, some  sulfonamide -resistant

bacteria do not require para-aminobenzoic acid (PABA), an important precursor

for the synthesis of folic acid and nucleic acids in bacteria inhibited by

sulfonamides, instead, like mammalian cells, they turn to using preformed folic

acid.

4. Reduced drug accumulation: by decreasing drug permeability or increasing

active efflux (pumping out) of the drugs across the cell surface . These pumps

within the cellular membrane of certain bacterial species are used to pump

antibiotics out of the cell before they are able to do any damage. They are often

activated by a specific substrate associated with an antibiotic, as

in fluoroquinolone resistance.

5. Ribosome splitting and recycling: for example, drug-mediated stalling of the

ribosome by lincomycin and erythromycin unstalled by a heat shock protein

found in Listeria monocytogenes, which is a homologue of HflX from other

bacteria. Liberation of the ribosome from the drug allows further translation and

consequent resistance to the drug