How can the bugs become resistant? <1>
The discovery of antibiotics was thought to be the end of all infectious diseases. Unfortunately, bacteria found ways to develop resistance mechanisms to evade antibiotics! Generally, bacteria can avoid antibiotic activity through four main mechanisms. These include target modification, efflux pumps, immunological mechanisms, and enzyme-catalyzed destruction.
Imagine modified from (Wright GD, 2010) <1>
1. Target Modification <1>
Target modification involves mutations that 1) change the active site of the antibiotic, or 2) cause production of enzymes that degrade antibiotics. For example, fluoroquinolone (FQ) antibiotics bind to DNA replication machinery to kill bacteria. If bacteria developed mutations to change the structure of the DNA machinery to avoid FQ binding, the bacteria would become resistant to FQ.
2. Immunological Mechanisms <1>
Immunological mechanisms involve binding of proteins to the antibiotic to prevent its activity. For example, some bacteria can produce ribosomal protection proteins (RPPs). RPPs work to displace antibiotics that are situated on the bacteria <2>.
3. Efflux <1>
Efflux involves development of protein pumps to continually remove antibiotics from inside the cell. The efflux pumps work to continuously remove the antibiotic to prevent it from reaching its target site.
4. Enzymatic Degradation <1>
Enzyme-catalyzed destruction involves actively producing substances to destroy antibiotics. The most common example involves the production of β-lactamases. Beta-lactamases actively cleave the β-lactam ring found on penicillin and cephalosporin antibiotics. Beta-lactam rings represent an essential component for activity. Destroying the β-lactam ring means the antibiotic will no longer work.
References:
1. Wright GD. Q&A: antibiotic resistance: where does it come from and what can we do about it? BMC Biol 2010; 8:123.
2. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett's principles and and practice of infectious diseases. 9th ed. Philadelphia: Churchill Livingstone/Elsevier; 2009.
1. Wright GD. Q&A: antibiotic resistance: where does it come from and what can we do about it? BMC Biol 2010; 8:123.
2. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett's principles and and practice of infectious diseases. 9th ed. Philadelphia: Churchill Livingstone/Elsevier; 2009.