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Mechanisms of Antibacterial Resistance

Mechanisms of Antibacterial Resistance

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Mechanisms of Resistance
Antibiotic resistance can be intrinsic* – The mechanism of resistance is inherent to the structure or physiology of the bacteria. – For example, a bacterium that does not have penicillin-binding proteins will be insensitive to penicillins. Antibiotic resistance can be acquired* – The mechanism is acquired via mutations in bacterial chromosomal genes or horizontal gene transfer. – For example, the genes for antibiotic resistance can be found on plasmids that are easily transferred among bacteria.
Key Mechanisms:
Be aware that bacteria may use multiple forms of resistance.
  • Some bacteria produce enzymes that modify or destroy the antibiotic.
– For example, Aminoglycoside modifying enzymes (AMEs) render the aminoglycoside antibiotics ineffective by altering the chemical structure of the drugs, rendering them ineffective. – Beta-lactamases, on the other hand, destroy bonds of the beta-lactam ring.
  • Bacteria can also prevent drugs from reaching their targets; this is an especially effective mechanism against antibiotics that target the cytoplasmic membrane or intracellular structures.
– For example, E. coli can reduce membrane permeability via porin changes. – Or, bacteria can increase production of efflux pumps, which extrude antibiotic molecules. For example, E. coli can upregulate these pumps to effectively decrease the cytoplasmic concentration of tetracycline.
  • Modification of the drug's target to bypass or alter affinity is another effective means of resistance.
– As an example of altered affinity, Methicillin-Resistant Staphylococcus aureus (MRSA) has a low-affinity version of the Penicillin-binding Protein; thus, beta-lactams are ineffective. – As an example of bypassing a drug's target, fluoroquinolone resistance is achieve via alteration in the genes for the drugs' target enzymes.
  • Complex changes in bacterial cell physiology can also lead to global resistance.
– For example, multi-step resistance acquisition appears to play an important role in resistance to daptomycin and vancomycin.

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