Antimicrobial Modes of Action

Antimicrobial chemicals work to disrupt the cell membrane and cell wall synthesis, inhibit protein synthesis, and inhibit of nucleic acid synthesis.

Antimicrobial drugs take advantage of inherent biological differences between animals and the microbial pathogens that infect them. Each group of antibiotic drugs has a specific target in bacterial cells. When disruption of the bacterial target causes microbial replication to fail inhibiting the growth of bacteria, the antimicrobial drug is bacteriostatic. When the antimicrobial drug results in cell death it is bactericidal. The integrity or synthesis of cell walls, cell membrane stability, and protein or nucleic acid synthesis are common targets for disruption with antimicrobials.

While they differ from each other, bacterial and fungal cells both have cell walls, while animal cells do not. Therefore, much antimicrobial activity targets cell wall biochemistry. There is an interwoven layer of a polymer of sugars and amino acids called peptidoglycan in bacterial cell walls. Some of the first widely used antibiotics disrupt the synthesis of peptidoglycan by interrupting the enzyme responsible for linking the subunits of the polymers.

Penicillin, referring to a group of broad-spectrum antibiotics that inhibit bacterial cell wall synthesis, and its derivatives are members of this group of antibiotics and are still used today. The cell wall is susceptible to other antibiotic modes of action. For example, vancomycin causes cell wall fragility by inhibiting cross-linkage of peptidoglycan.

Activity of Penicillin

Penicillin and its derivatives are able to inhibit the formation of bacterial cells walls by disrupting the enzymes that assemble them.
Antimicrobials that disrupt the cell membrane are less common because their lack of specificity causes serious complications in humans and other animals. The antibiotic polymyxin has detergent-like properties that disrupt the membranes of gram-negative bacteria. Despite toxicity when taken internally, polymyxin antibiotics are effective at preventing infections when used as a topical ointment applied to skin wounds.

Antimicrobials that target protein synthesis or nucleic acid synthesis are also effective. Prokaryotic protein-synthesizing ribosomes are constructed with different subunits than in eukaryotes, providing targets with reduced human toxicity. Erythromycin is a very common antibiotic used to treat a wide range of infections. It binds to a bacterial ribosomal subunit, where it disrupts the formation of peptide bonds between amino acids, thus inhibiting protein synthesis. Two other common antibiotics, tetracycline and aminoglycoside, interrupt protein synthesis by binding to a different ribosomal subunit. Aminoglycoside disrupts bacterial protein synthesis and is used to treat aerobic gram-negative infections. Tetracycline inhibits bacterial protein synthesis and is prescribed for a wide range of infections. Tetracycline blocks amino acids from associating with the ribosome, while aminoglycosides disrupt the ribosome from reading the RNA template correctly, causing amino acid substitutions. Both result in nonfunctional protein synthesis.

Since all life on Earth uses the same DNA, blocking nucleic acid synthesis works indirectly by disrupting enzymes involved in managing the arrangement of DNA in bacterial cells. Bacteria have a class of enzymes used to uncoil their single chromosome during DNA replication and during transcription to RNA. Antibiotics such as quinolones inhibit these enzymes and thus inhibit both DNA replication and protein synthesis.

Activity of Tetracycline

Tetracyclines operate by disrupting the synthesis of proteins in the ribosomes. Without these proteins, bacteria are unable to properly develop and grow.
Several antibiotics function as antimetabolites. An antimetabolite is a chemical that impedes the use of the appropriate metabolite in a biochemical pathway. By disrupting the pathway, these antibiotics inhibit production of its products. The targeted pathways may disrupt cell wall, protein, or nucleic acid synthesis. Sulfonamide antibiotics, for example, have a similar chemical structure to a precursor of the coenzyme folic acid and therefore disrupt bacterial synthesis of folic acid. Folic acid, in turn, is critical to the replication of DNA. By inhibiting the synthesis of folic acid, sulfonamides inhibit DNA and bacterial replication.
Microbial metabolism can be disrupted in many ways. The cell wall is a primary target for many antimicrobials because animal cells do not have one.