Mechanisms of Action of Antibacterial Drugs

A number of bacterial processes utilize enzymes or structures that are either different, absent, or not commonly found in eukary-otic cells. Several microbial processes, including the synthesis of bacterial cell walls, proteins, and nucleic acids, metabolic path-

Cell Wall (peptidoglycan) Synthesis

ß-lactam drugs

Vancomycin

Bacitracin

21.3 Mechanisms of Action of Antibacterial Drugs 511

, Nucleic Acid Synthesis

Fluoroquinolones Rifamycins

21.3 Mechanisms of Action of Antibacterial Drugs 511

, Nucleic Acid Synthesis

Fluoroquinolones Rifamycins

Cell Wall (peptidoglycan) Synthesis

ß-lactam drugs

Vancomycin

Bacitracin

Cell Membrane Integrity

Polymyxin B

Metabolic Pathways (folate biosynthesis)

Sulfonamides Trimethoprim

Cell Membrane Integrity

Polymyxin B

Metabolic Pathways (folate biosynthesis)

Sulfonamides Trimethoprim

Protein Synthesis

Aminoglycosides

Tetracyclines

Macrolides

Chloramphenicol

Lincosamides

Oxazolidinones

Streptogramins

Figure 21.2 Targets of Antibacterial Medications ways, and the integrity of the cytoplasmic membrane, are the targets of most antimicrobial drugs (figure 21.2).

This section will discuss the bacterial processes commonly targeted by antimicrobial medications. To illustrate how these targets are affected, the mechanism of action of some of the most widely used antimicrobials will be described (table 21.2, p. 513). A group of antibiotics called p-lactam drugs will be covered in the greatest detail, because they serve as excellent examples of some of the important features of antimicrobials.

Antibacterial Medications that Inhibit Cell Wall Synthesis

Bacterial cell walls are unique in that they contain peptidoglycan, a three-dimensional structure composed of strands of alternating subunits of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) (see figure 3.32). These strands, called glycan chains, are interconnected through peptide bridges between the amino acid side chains of NAM. The intact structure provides the cell the rigidity to maintain integrity. Because peptidogly-can is specific to bacteria, drugs that interfere solely with cell wall synthesis do not affect eukaryotic cells, and they usually have a very high therapeutic index. ■ peptidoglycan, p. 58

A number of medically useful antimicrobial drugs interfere with cell wall biosynthesis (figure 21.3). Among these, the most widely used are the penicillins and the cephalosporins. They are members of an even larger group, collectively referred to as b-lactam drugs, which also includes the monobactams and the carbapenems; these drugs all have a shared chemical structure called a b-lactam ring (figure 21.4). Other drugs that target peptidoglycan synthesis include vancomycin and bacitracin.

The P-Lactam Drugs

The P-lactam drugs irreversibly inhibit enzymes involved in the final steps of cell wall synthesis. They have been extensively studied because they are such important antimicrobial agents, having very few side effects other than allergic reactions. Their

Nester-Anderson-Roberts: I III. Microorganisms and I 21. Antimicrobial I I © The McGraw-Hill

Microbiology, A Human Humans Medications Companies, 2003

Perspective, Fourth Edition

512 Chapter 21 Antimicrobial Medications b-lactam drugs

Interfere with the formation of the peptide side chains between adjacent strands of peptidoglycan by inhibiting penicillin-binding proteins

Peptidoglycan (cell wall)

Vancomycin

Binds to the amino acid side chain of NAM molecules, interfering with peptidoglycan synthesis

Cytoplasmic membrane

Peptidoglycan (cell wall)

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