Antibiotic Resistance

Mechanism of Resistance

There are multiple genetic, idiopathic (unknown), and iatrogenic (caused by a physician) factors contributing to the crisis of antibiotic resistance.

There are four main mechanisms by which bacteria acquire resistance:

• Enzymatic degradation of the drug (the bacteria break down the drug)
• Modification of the drug's target
• Decreased permeability (bacteria change borders to block antibiotics from entering)
• Active export of the drug (bacteria pump antibiotics out of cells)

Bacterial and human cells differ in a few key ways. Bacteria have a cell wall, a structure not present in human cells, and it is this wall that is the target of antibiotics. However, there are multiple ways for bacteria to protect themselves. To synthesize cell walls, bacteria use an enzyme called a penicillin binding protein (PBP). Some beta-lactam antibiotics, such as penicillin, bind to the PBPs to prevent synthesis of the wall, eventually leading to cell destruction. Bacteria can fight this attack in two different ways. Some bacteria can produce beta-lactamase, an enzyme that destroys the active portion of the antibiotic. Other bacteria produce modified PBPs, which allow beta-lactam antibiotics to bind without being able to inhibit cell wall synthesis.

Bacterial cell membranes are permeable to different components in their environment. By altering what can/cannot pass through the cell membrane, destruction with an antibiotic can be fought off because the drug will not be able to enter inside the cell in a concentration strong enough to be effective. Multidrug-resistant pumps actively export drugs that enter the bacteria. Bacteria take in surrounding materials and pump out the antibiotic from within the cell.

Genetically Mediated Antibiotic Resistance

Most mechanisms of bacterial resistance to antibiotics are due to genetic modification, including chromosome-mediated, plasmid-mediated, or transposon-mediated resistance. Clinically, plasmid-mediated resistance is of greatest concern because of the opportunity for plasmids to code for resistance to multiple antibiotics. Chromosome-mediated resistance occurs through spontaneous mutations in the DNA of the bacterium. A mutation in a gene [Page 23]that codes for the binding site of the antibiotic, or the transport proteins that allow the drug to enter the cell, can make the bacteria resistant.

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