Antibiotics are medicines designed to combat bacterial infections. While their effectiveness is widely recognized, understanding how they work at a cellular level provides insight into their importance in modern medicine. Different types of antibiotics neutralize bacteria by targeting unique structures or processes absent in human cells.
Targeting the Bacterial Cell Wall
Bacterial cells possess a rigid outer layer called the cell wall, which provides structural support and protection. This cell wall is composed primarily of peptidoglycan, a complex polymer of sugars and amino acids that human cells do not have. This structural difference makes the bacterial cell wall an ideal target for selective antibiotic action.
Many common antibiotics, such as penicillin and other beta-lactam antibiotics (e.g., cephalosporins, monobactams, and carbapenems), interfere with peptidoglycan synthesis. These drugs contain a beta-lactam ring that binds to penicillin-binding proteins (PBPs), enzymes responsible for cross-linking peptidoglycan strands during cell wall construction. By inhibiting PBPs, antibiotics prevent proper cell wall assembly, leading to a weakened structure. This compromised wall cannot withstand the bacterium’s internal osmotic pressure, causing the cell to swell and burst. This action is bactericidal, directly killing bacterial cells.
Interfering with Bacterial Protein Synthesis
Proteins are fundamental molecules that carry out nearly all cellular functions, including growth, repair, and reproduction. Bacteria rely on ribosomes to synthesize these proteins from genetic instructions. Bacterial ribosomes are structurally different from human ribosomes, allowing antibiotics to selectively target them.
Antibiotics disrupt bacterial protein synthesis by interfering with various stages. Some, like tetracyclines, bind to the smaller 30S ribosomal subunit, preventing transfer RNA (tRNA) molecules from attaching to the ribosome, blocking amino acid addition. Other antibiotics, such as macrolides (e.g., erythromycin, azithromycin) and chloramphenicol, bind to the larger 50S ribosomal subunit. Macrolides can block the exit tunnel for new protein chains, leading to premature termination. Chloramphenicol prevents peptide bond formation, halting protein elongation.
Aminoglycosides, like streptomycin, also bind to the 30S subunit, causing misreading of the genetic code and premature termination. Some protein synthesis inhibitors, like aminoglycosides, are bactericidal. Others, such as tetracyclines and macrolides, are bacteriostatic, meaning they inhibit bacterial growth and reproduction without directly killing the cells.
Disrupting Bacterial Genetic Material
Bacteria depend on their genetic material, DNA and RNA, to store instructions for life processes and to replicate. Interfering with these processes can halt bacterial growth and lead to cell death. The enzymes involved in bacterial DNA replication and RNA transcription differ sufficiently from human enzymes, providing targets for selective antibiotic action.
Fluoroquinolones target bacterial DNA replication. These drugs inhibit bacterial DNA gyrase and topoisomerase IV, enzymes responsible for unwinding and supercoiling DNA, necessary for replication and repair. By blocking these enzymes, fluoroquinolones cause breaks in the bacterial DNA, preventing multiplication.
Rifamycins, such as rifampin, inhibit bacterial RNA polymerase, the enzyme responsible for transcribing DNA into RNA. Without functional RNA, bacteria cannot produce necessary proteins, leading to cell death. Antibiotics that disrupt bacterial genetic material are bactericidal, as they directly lead to the demise of the bacterial cell.
Targeting Bacterial Metabolism and Membranes
Bacteria rely on specific metabolic pathways to produce essential compounds required for their survival and growth. Human cells often use different metabolic pathways or can obtain these compounds from their environment, making bacterial metabolism a potential antibiotic target. Sulfonamides and trimethoprim are examples of antibiotics that interfere with bacterial folic acid synthesis. Folic acid is a coenzyme required for the synthesis of DNA and RNA building blocks in bacteria. By blocking different steps in the folic acid synthesis pathway, these antibiotics prevent bacteria from producing necessary genetic material, thereby inhibiting their growth. This action is bacteriostatic.
Bacterial cells are enclosed by a cell membrane, and some bacteria have an additional outer membrane. These membranes control the passage of substances into and out of the cell. Polymyxins are a class of antibiotics that disrupt the integrity of bacterial membranes. They interact with the outer membrane in Gram-negative bacteria and then disrupt both the outer and inner membranes. This disruption leads to leakage of the bacterial cell’s contents, causing cell damage and death.
Daptomycin, another membrane-targeting antibiotic, inserts into the bacterial cell membrane, causing depolarization and loss of membrane potential, which leads to bacterial cell death. Polymyxins and daptomycin are bactericidal.