Antibiotics are medicines designed to combat bacterial infections. These drugs work by targeting and disrupting specific processes within bacterial cells, either killing them or inhibiting their growth, allowing the body’s immune system to clear the infection.
Targeting the Bacterial Cell Wall
Many antibiotics target the bacterial cell wall, a rigid outer layer absent in human cells. Beta-lactam antibiotics, such as penicillins and cephalosporins, contain a beta-lactam ring structure important for their activity.
These antibiotics interfere with the synthesis of peptidoglycan, a unique polymer that provides structural integrity to the bacterial cell wall. Beta-lactams bind to enzymes called penicillin-binding proteins (PBPs), which are responsible for cross-linking peptidoglycan strands during cell wall formation. By inhibiting these PBPs, the antibiotics prevent the bacteria from building or maintaining their protective barrier, leading to a weakened cell wall and ultimately cell lysis and death.
Disrupting Bacterial Protein Production
Another way antibiotics combat bacteria is by interfering with their protein synthesis machinery. Proteins are essential for all cellular functions, and bacteria produce them using structures called ribosomes. Bacterial ribosomes are structurally different from human ribosomes, specifically having 70S ribosomes compared to the 80S ribosomes found in human cells.
Antibiotics like tetracyclines, macrolides, and aminoglycosides exploit this difference. Tetracyclines bind to the 30S ribosomal subunit, preventing the attachment of transfer RNA (tRNA) and thus blocking protein synthesis. Macrolides and lincosamides, in contrast, bind to the 50S ribosomal subunit, inhibiting the movement of ribosomes along messenger RNA (mRNA) or preventing peptide bond formation, which stops the growth of the protein chain. Aminoglycosides also bind to the 30S ribosomal subunit, causing misreading of mRNA and leading to the production of faulty proteins, often resulting in bacterial cell death.
Interfering with Bacterial Genetic Material
Some antibiotics work by disrupting the genetic processes within bacteria, specifically DNA replication and RNA transcription. These processes are necessary for bacteria to multiply and produce the components they need to survive. Fluoroquinolones and rifamycins are examples of antibiotics that target bacterial genetic material.
Fluoroquinolones interfere with bacterial DNA synthesis by inhibiting bacterial type II topoisomerases, such as DNA gyrase and topoisomerase IV. These enzymes are responsible for managing the coiling and uncoiling of DNA strands, which is necessary for DNA replication and repair. By disrupting these enzymes, fluoroquinolones prevent bacteria from accurately replicating their DNA, leading to cell death. Rifamycins, on the other hand, target bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase, an enzyme that initiates RNA transcription. This binding blocks the path of the newly forming RNA, preventing the bacteria from producing essential proteins and other cellular components.
Blocking Essential Bacterial Processes
Beyond targeting structural components or genetic machinery, some antibiotics interfere with unique metabolic pathways present in bacteria but absent in human cells. Sulfonamides, also known as sulfa drugs, are an example of this mechanism.
Sulfonamides block the synthesis of folic acid, a compound that bacteria need to produce DNA, RNA, and proteins. Bacteria must synthesize their own folic acid from precursors, while human cells obtain it from their diet. Sulfonamides act as competitive inhibitors by mimicking para-aminobenzoic acid (PABA), an early intermediate in the bacterial folic acid synthesis pathway, thereby preventing the enzyme dihydropteroate synthase from functioning correctly. This disruption halts bacterial growth by starving them of necessary building blocks for their genetic material.
Why Antibiotics Selectively Target Bacteria
The effectiveness of antibiotics in treating infections without significantly harming human cells lies in a principle called selective toxicity. These drugs are designed to target structures or processes unique to bacteria or significantly different from those found in human cells.
For instance, the bacterial cell wall, made of peptidoglycan, is a structure completely absent in human cells, making it a target for antibiotics like beta-lactams. Similarly, bacterial ribosomes (70S) are structurally distinct from human ribosomes (80S), enabling antibiotics such as tetracyclines and macrolides to selectively inhibit bacterial protein production. The unique metabolic pathway for folic acid synthesis in bacteria, which is not present in humans who acquire folic acid through diet, allows sulfonamides to interfere with bacterial growth without affecting human cells. These examples illustrate how antibiotics leverage fundamental biological differences to achieve their therapeutic effects.