How Antimicrobial Drugs Work: Videos & Practice Problems

Selective toxicity enables antibacterial drugs to target bacterial structures like the peptidoglycan cell wall, unique membrane lipids, bacterial DNA/RNA synthesis enzymes, 70S ribosomes, and folic acid metabolic pathways, sparing human cells. These mechanisms exploit differences between prokaryotic bacteria and eukaryotic human cells, making bacteria more susceptible than fungi or viruses. Antibacterials are classified as bactericidal, killing bacteria by disrupting cell walls or membranes, or bacteriostatic, inhibiting protein synthesis or metabolism to halt growth, allowing the immune system to clear infections. Understanding these targets is crucial for effective antimicrobial therapy and combating antibiotic resistance.

Selective Toxicity

Selective toxicity is a fundamental principle in antimicrobial therapy, referring to the ability of drugs to kill or inhibit microbes without causing harm to human cells. This concept is crucial because effective antimicrobial agents must target features unique to microbes, ensuring safety and efficacy in treating infections. Achieving selective toxicity is particularly challenging with eukaryotic pathogens, such as fungi and parasites, due to their cellular similarities to human cells. Viruses also pose difficulties because they rely on the host's cellular machinery for replication, limiting the number of unique viral targets.

Bacterial infections, however, present more opportunities for selective toxicity because bacterial cells differ significantly from human cells at the molecular and structural levels. There are five primary targets for antibacterial drugs that exploit these differences. First, the bacterial cell wall, composed mainly of peptidoglycan, is absent in human cells, making it an ideal target. Drugs that inhibit peptidoglycan synthesis disrupt the bacterial cell wall, leading to cell death.

Second, the bacterial cell membrane contains unique lipids distinct from those in human membranes. Targeting these bacterial-specific membrane components can selectively damage bacterial cells. Third, nucleic acid synthesis is another critical target. Although both bacteria and humans synthesize DNA and RNA, they use different enzymes for replication and transcription. Antibacterial agents can inhibit bacterial DNA gyrase or RNA polymerase, enzymes not found in human cells, thereby blocking bacterial nucleic acid synthesis.

Fourth, protein synthesis is targeted by exploiting differences in ribosome structure. Bacteria possess 70S ribosomes, whereas human cells have 80S ribosomes. Antibiotics that bind specifically to bacterial ribosomes can inhibit translation without affecting human protein synthesis. Finally, metabolic pathways unique to bacteria, such as folic acid synthesis, provide selective targets. Unlike humans, who obtain folic acid through diet, bacteria must synthesize it. Drugs that inhibit enzymes in the folic acid synthesis pathway effectively starve bacteria of this essential nutrient.

These five mechanisms can be broadly categorized based on their effects on bacteria. Drugs targeting the cell wall, cell membrane, and nucleic acid synthesis are typically bactericidal, meaning they kill bacteria directly. In contrast, agents that inhibit protein synthesis and metabolic pathways are usually bacteriostatic; they halt bacterial growth and replication, allowing the immune system to eliminate the infection.

Understanding these mechanisms of selective toxicity is essential for developing and using antibacterial drugs effectively. By targeting bacterial-specific structures and processes, these drugs minimize harm to human cells while combating infections. This knowledge also guides the selection of appropriate therapies based on whether a bactericidal or bacteriostatic effect is desired in clinical treatment.

How Antimicrobial Drugs Work Example 1

Understanding the mechanisms of antibacterial drugs is crucial for distinguishing between bactericidal and bacteriostatic effects. Antibacterial agents target various components of bacterial cells, influencing whether they kill the bacteria directly or merely inhibit their growth. For instance, drugs that interfere with folic acid synthesis act on a metabolic pathway essential for bacterial growth. Since these drugs halt bacterial proliferation without killing the cells outright, they are classified as bacteriostatic. This means they pause cell growth, allowing the immune system to eliminate the infection.

In contrast, targeting the peptidoglycan layer, a vital component of the bacterial cell wall, results in a bactericidal effect. Disrupting the cell wall compromises the bacterium’s structural integrity, leading to cell lysis due to osmotic pressure. Similarly, drugs that damage the cell membrane lipids and sterols also exhibit bactericidal activity by causing membrane disruption and cell death.

When antibacterial drugs inhibit the 70S ribosome, which is responsible for protein synthesis in bacteria, the effect is typically bacteriostatic. By preventing translation, these drugs stop bacterial growth but do not directly kill the cells. Lastly, drugs targeting topoisomerase, an enzyme essential for DNA replication and nucleic acid synthesis, are bactericidal. Inhibiting topoisomerase prevents DNA replication, leading to bacterial cell death.

It is important to note that bacteriostatic drugs rely on the host’s immune system to clear the infection. By halting bacterial growth, these drugs provide the immune system with the opportunity to eliminate the pathogens effectively. This interplay highlights the significance of both drug action and immune response in treating bacterial infections.

When identifying ways a drug may be selectively toxic, why is bacterial protein synthesis a good potential target?

• A. Bacteria and eukaryotes use different tRNAs.
• B. There are many differences between bacterial 70s ribosomes and eukaryotic 80s ribosomes.
• C. The genetic code between bacteria and eukaryotes is different, allowing drugs to target bacterial-specific codons.
• D. Bacterial ribosomes often bind to RNA and initiate translation before transcription is complete.

Answer: (A)

Here’s what students ask on this topic:

What is selective toxicity and why is it important in antimicrobial drug therapy?

Selective toxicity refers to the ability of antimicrobial drugs to target and kill microbial cells without harming human cells. This concept is crucial because it allows the treatment of infections by specifically attacking features unique to microbes, such as bacteria, while sparing human tissues. For example, bacteria have a peptidoglycan cell wall, which human cells lack, making it an ideal target. Selective toxicity is more challenging for eukaryotic pathogens and viruses because they share more cellular machinery with humans or use human cells to replicate. Understanding selective toxicity helps in designing drugs that are effective against microbes but safe for patients, minimizing side effects and improving treatment outcomes.

What are the main bacterial targets for antibacterial drugs that enable selective toxicity?

Antibacterial drugs exploit five main targets unique to bacteria to achieve selective toxicity: (1) the peptidoglycan cell wall, which human cells do not have; (2) the bacterial cell membrane, which contains unique lipids different from human membranes; (3) enzymes involved in bacterial DNA and RNA synthesis, which differ from those in human cells; (4) the 70S ribosomes used by bacteria for protein synthesis, distinct from the 80S ribosomes in human cells; and (5) metabolic pathways such as folic acid synthesis, which bacteria must perform but humans obtain from their diet. Targeting these differences allows drugs to kill or inhibit bacteria without damaging human cells.

How do bactericidal and bacteriostatic drugs differ in their mechanisms of action?

Bactericidal drugs kill bacteria directly by disrupting essential structures like the cell wall or cell membrane, leading to bacterial death. Examples include drugs that inhibit peptidoglycan synthesis, causing the bacterial cell to lyse. In contrast, bacteriostatic drugs do not kill bacteria outright but inhibit their growth and reproduction by targeting processes such as protein synthesis or metabolic pathways. This pause in growth allows the immune system to eliminate the infection. Understanding whether a drug is bactericidal or bacteriostatic is important for clinical decisions, especially in immunocompromised patients where bactericidal drugs may be preferred.

Why is it more difficult to develop selectively toxic drugs against eukaryotic pathogens and viruses compared to bacteria?

Developing selectively toxic drugs against eukaryotic pathogens (like fungi and parasites) and viruses is challenging because these organisms share more cellular and molecular similarities with human cells. Eukaryotic pathogens have similar cellular structures and metabolic pathways as human cells, making it harder to find unique targets that drugs can attack without harming human tissues. Viruses are even more difficult because they hijack human cellular machinery to replicate, so targeting viral processes often risks damaging host cells. In contrast, bacteria are prokaryotes with distinct features such as peptidoglycan cell walls and 70S ribosomes, providing clearer targets for selective toxicity.

How does targeting folic acid synthesis in bacteria provide selective toxicity?

Bacteria synthesize their own folic acid, which is essential for DNA and RNA synthesis, whereas humans obtain folic acid through their diet and do not synthesize it. Antibacterial drugs that inhibit enzymes involved in bacterial folic acid synthesis can block bacterial growth without affecting human cells. This difference in metabolic pathways allows selective toxicity. For example, sulfonamides inhibit bacterial folic acid production, effectively stopping bacterial replication while sparing human cells, making this pathway an important target for antimicrobial therapy.

What role do bacterial ribosomes play as a target for antimicrobial drugs?

Bacterial ribosomes are 70S in size, composed of 50S and 30S subunits, which differ structurally from the 80S ribosomes found in human cells. This difference allows antimicrobial drugs to selectively bind to bacterial ribosomes and inhibit protein synthesis without affecting human ribosomes. Drugs like tetracyclines and macrolides exploit this difference to block bacterial translation, halting protein production and bacterial growth. Targeting bacterial ribosomes is a key strategy for bacteriostatic drugs, which stop bacterial proliferation and allow the immune system to clear the infection.