Bacteria often become resistant through different kinds of mechanisms. One kind of mechanism is never confined to any specific class of antibiotics. Different resistance mechanisms are used in different bacteria to confront the same antibiotics.
1. Prevention of Drug’s Entry into the Cell:
Many gram-negative bacteria are unaffected by Penicillin G because it cannot penetrate the envelope’s outer membrane. This is due to genetic mutations in bacteria that lead to changes in Penicillin-binding proteins present in bacteria.
Mycobacterium species resist many drugs because of the high content of Mycolic acids in a complex lipid layer outside their peptidoglycan wall. This layer is impermeable to most water-soluble drugs such as Sulfonamide.
2. Driving out the Drug after it has entered the Cell:
Some pathogens have plasma membrane translocases, often called efflux pumps that expel drugs. Because these pumps are relatively non-specific and can pump many different drugs, these transport proteins are commonly known as multi-drug-resistance pumps. Such systems are present in E. coli, P. aerunginosa, and S. aureus.
3. Degrading the Structure of Antibiotics:
In Penicillin, the most crucial feature is the presence of the β-Lactam ring, which is essential for its bioactivity. Many penicillin-resistant bacteria produce penicillinase (also called β-Lactamase), an enzyme that inactivates the antibiotics by hydrolyzing bond in the β-Lactam ring.
4. Altering the Structure of Antibiotics:
Drugs are also inactivated by three additions of chemical groups. For example, Chloramphenicol contains two hydroxyl groups that can be acetylated in a reaction catalyzed by the enzyme Chloramphenicol Acetyltransferase with Acetyl-CoA as the donor.
5. Bypassing the Sequence Inhibited by Antibiotics:
Resistant bacteria may use any other alternative to bypass the sequence or step inhibited by the antibiotics. For example, some bacteria are resistant to Sulfonamide because they simply pick up the already formed folic acid from their surroundings rather than synthesizing it themselves.
Antibiotic Resistance, if persists and increases then it will take our chemotherapeutic research twenty years back because all the antibiotics produced and discovered so far, will no longer of any use and we would enter a post-antibiotic era.