Antibiotics
Under most conditions, bacteria die without an intact cell wall. Since human cells completely lack a cell wall, this is an important target for antibiotics. To understand how these antibiotics work, though, it's necessary to understand how bacteria make cell walls. There are several steps in the process. Initially the "building blocks" (N-acetyl glucosamine and N-acetyl muramic acid) of the cell wall are made in the cytoplasm (the fluid that fills cells). These building blocks are then transported across the cell membrane using a carrier molecule, where they are next joined to an existing long chain of building blocks (in a process called transglycosylation) and are crosslinked to another long chain (in a process called transpeptidation). Bacteria make new cell wall material only when they are growing. Therefore, antibiotics that disrupt this process are typically only effective on growing cells.
Different antibiotics target different steps in cell-wall synthesis; for example, penicillin inhibits transpeptidation. Vancomycin inhibits transglycosylation and transpeptidation. Bacitracin inhibits the regeneration of the carrier required for moving the building blocks of the cell wall across the membrane.
Living and growing cells require a constant supply of new proteins. Without new proteins, a cell will either stop growing, or it may even die. In both bacterial and human cells, new proteins are manufactured on ribosomes, in a process called translation. However, bacterial ribosomes differ enough from human ribosomes that antibiotics can effectively target them.
Ribosomes require messenger RNA (mRNA), transfer RNA (tRNA), and amino acids (the building blocks of proteins) in order to make proteins. During translation, the ribosome slides along the mRNA in three-nucleotide steps; tRNAs bring in the appropriate amino acids to allow the protein to be made.
Streptomycin is an example of an antibiotic that targets the ribosome. This antibiotic binds to a ribosomal protein and interferes with the movement of the ribosome along the mRNA. As a consequence, streptomycin makes protein synthesis less accurate. Erythromycin is another example of an antibiotic that binds to ribosomal RNA. Erythromycin terminates protein synthesis prematurely, meaning that few, if any, functional proteins are produced by the cell. Tetracycline binds to the ribosome and interferes with a new tRNA (containing an amino acid) coming into the ribosome.
In order for a cell to divide, it must copy its DNA. An antibiotic that prevents DNA synthesis will therefore keep a bacterial population from growing, and may kill affected cells. Copying DNA in a cell is a complex process. The DNA synthesis machinery includes enzymes called DNA gyrase and topoisomerase, which help twist and untwist DNA during replication. These enzymes accomplish this feat by cutting the DNA, then "gluing" the cut ends back together. A similar process occurs in human cells, but the bacterial and human enzymes involved are different enough that some antibiotics can target the bacterial enzymes without affecting the human enzymes.
Ciprofloxacin and related antibiotics work by allowing topoisomerases to cut DNA but not "glue" the ends back together. The result is that the bacterium can no longer replicate its DNA, keeping the bacterial population in check. In addition, in some bacteria, this DNA damage may also activate a process that leads to the death of the bacterial cell.
Bacteria must continuously make RNA in order to survive. RNA plays many roles in the cell, including acting as a messenger between the information coded in the DNA and the protein-making ribosomes. RNA synthesis requires an enzyme called RNA polymerase, and this enzyme is critical in all types of cells. RNA polymerases differ enough between bacteria and human cells that the bacterial version can be targeted by some antibiotics. The antibiotic rifampin, for example, binds to bacterial RNA polymerase and prevents it from making RNA. Consequently, this leads to a loss of new protein synthesis. Since a continuous supply of new proteins is typically required for cellular survival, these antibiotics cause the death of the bacterial cell.
Folic acid is an essential vitamin that is required for many chemical reactions inside cells. Humans get folic acid from our diet; bacteria make their own from scratch. This difference helps explain why another group of antibiotics, the sulfonamides, are able to selectively kill bacteria. Sulfonamides work by mimicking the compound used by bacteria to make folic acid (para-amino benzoic acid or PABA). The sulfa drugs bind to an enzyme that is required to convert PABA to tetrahydrofolic acid and disable the enzyme so it can no longer function.
Sulfonamides are often given together with another antibiotic, trimethoprim, which inhibits a different stage of folic acid synthesis. In this case, the enzymes are found in both bacteria and humans, but the enzymes are different enough that trimethoprim binds to the bacterial enzyme with 60,000 times higher affinity (preference) for the bacterial versus human enzyme.6 The use of these two antibiotics provides double the assurance that the pathway will be disabled and reduces the likelihood of resistance developing.
A more restricted class of antibiotics, which work only on Mycobacterium tuberculosis and closely related bacteria, interfere with synthesis of components of the mycobacterial cell wall. One of these drugs, isoniazid, is an inactive chemical until it enters the bacterial cell. M. tuberculosis contains an enzyme that activates the antibiotic, which then goes on to damage enzymes that would otherwise assist in synthesizing the mycobacterial cell wall. Another drug, ethambutanol, inhibits the synthesis of a different component of the mycobacterial cell wall.
The presence of an intact membrane is critical for cellulars survival. The cell membrane acts as a barrier between the organism and the environment, preventing the loss of essential chemicals. Therefore, antibiotics that destroy membrane integrity should be very effective. Unfortunately, the membranes surrounding bacterial and human cells are quite similar, which is why antibiotics that target bacterial membranes also tend to harm human cells. Consequently, such antibiotics are typically restricted to use on the skin, the outer layer of which consists of dead cells that are unaffected by these antibiotics. Polymixin is an example of an antibiotic that disrupts cell membranes.
Different antibiotics target different steps in cell-wall synthesis; for example, penicillin inhibits transpeptidation. Vancomycin inhibits transglycosylation and transpeptidation. Bacitracin inhibits the regeneration of the carrier required for moving the building blocks of the cell wall across the membrane.
Living and growing cells require a constant supply of new proteins. Without new proteins, a cell will either stop growing, or it may even die. In both bacterial and human cells, new proteins are manufactured on ribosomes, in a process called translation. However, bacterial ribosomes differ enough from human ribosomes that antibiotics can effectively target them.
Ribosomes require messenger RNA (mRNA), transfer RNA (tRNA), and amino acids (the building blocks of proteins) in order to make proteins. During translation, the ribosome slides along the mRNA in three-nucleotide steps; tRNAs bring in the appropriate amino acids to allow the protein to be made.
Streptomycin is an example of an antibiotic that targets the ribosome. This antibiotic binds to a ribosomal protein and interferes with the movement of the ribosome along the mRNA. As a consequence, streptomycin makes protein synthesis less accurate. Erythromycin is another example of an antibiotic that binds to ribosomal RNA. Erythromycin terminates protein synthesis prematurely, meaning that few, if any, functional proteins are produced by the cell. Tetracycline binds to the ribosome and interferes with a new tRNA (containing an amino acid) coming into the ribosome.
In order for a cell to divide, it must copy its DNA. An antibiotic that prevents DNA synthesis will therefore keep a bacterial population from growing, and may kill affected cells. Copying DNA in a cell is a complex process. The DNA synthesis machinery includes enzymes called DNA gyrase and topoisomerase, which help twist and untwist DNA during replication. These enzymes accomplish this feat by cutting the DNA, then "gluing" the cut ends back together. A similar process occurs in human cells, but the bacterial and human enzymes involved are different enough that some antibiotics can target the bacterial enzymes without affecting the human enzymes.
Ciprofloxacin and related antibiotics work by allowing topoisomerases to cut DNA but not "glue" the ends back together. The result is that the bacterium can no longer replicate its DNA, keeping the bacterial population in check. In addition, in some bacteria, this DNA damage may also activate a process that leads to the death of the bacterial cell.
Bacteria must continuously make RNA in order to survive. RNA plays many roles in the cell, including acting as a messenger between the information coded in the DNA and the protein-making ribosomes. RNA synthesis requires an enzyme called RNA polymerase, and this enzyme is critical in all types of cells. RNA polymerases differ enough between bacteria and human cells that the bacterial version can be targeted by some antibiotics. The antibiotic rifampin, for example, binds to bacterial RNA polymerase and prevents it from making RNA. Consequently, this leads to a loss of new protein synthesis. Since a continuous supply of new proteins is typically required for cellular survival, these antibiotics cause the death of the bacterial cell.
Folic acid is an essential vitamin that is required for many chemical reactions inside cells. Humans get folic acid from our diet; bacteria make their own from scratch. This difference helps explain why another group of antibiotics, the sulfonamides, are able to selectively kill bacteria. Sulfonamides work by mimicking the compound used by bacteria to make folic acid (para-amino benzoic acid or PABA). The sulfa drugs bind to an enzyme that is required to convert PABA to tetrahydrofolic acid and disable the enzyme so it can no longer function.
Sulfonamides are often given together with another antibiotic, trimethoprim, which inhibits a different stage of folic acid synthesis. In this case, the enzymes are found in both bacteria and humans, but the enzymes are different enough that trimethoprim binds to the bacterial enzyme with 60,000 times higher affinity (preference) for the bacterial versus human enzyme.6 The use of these two antibiotics provides double the assurance that the pathway will be disabled and reduces the likelihood of resistance developing.
A more restricted class of antibiotics, which work only on Mycobacterium tuberculosis and closely related bacteria, interfere with synthesis of components of the mycobacterial cell wall. One of these drugs, isoniazid, is an inactive chemical until it enters the bacterial cell. M. tuberculosis contains an enzyme that activates the antibiotic, which then goes on to damage enzymes that would otherwise assist in synthesizing the mycobacterial cell wall. Another drug, ethambutanol, inhibits the synthesis of a different component of the mycobacterial cell wall.
The presence of an intact membrane is critical for cellulars survival. The cell membrane acts as a barrier between the organism and the environment, preventing the loss of essential chemicals. Therefore, antibiotics that destroy membrane integrity should be very effective. Unfortunately, the membranes surrounding bacterial and human cells are quite similar, which is why antibiotics that target bacterial membranes also tend to harm human cells. Consequently, such antibiotics are typically restricted to use on the skin, the outer layer of which consists of dead cells that are unaffected by these antibiotics. Polymixin is an example of an antibiotic that disrupts cell membranes.
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