BIO 205

Chapter 24
Antimicrobial Drugs
•Alexander Fleming’s Serendipitous Discovery of Penicillin
Ushered in the Era of Antibiotics

•Penicillium mold produces a substance that kills gram-positive

bacteria
Antimicrobial Agents Have a Number of Important
Properties

•Synthetic agents are made in a pharmaceutical

lab

•Antibiotics are products of or derived from living

microorganisms

•Semisynthetic drugs include synthetic and

antibiotic elements
Selective toxicity means that a drug should harm the pathogen but not the
host

•The toxic dose of a drug is the concentration causing harm to the host

•The therapeutic dose is the concentration eliminating pathogens in the

host

•Together, the toxic and therapeutic doses are used to formulate the
chemotherapeutic index
Drugs have a range of pathogens on which they will work
(antimicrobial spectrum)

•Broad spectrum drugs affect many taxonomic groups

•Narrow spectrum drugs affect only a few pathogens

The Synthetic Antibacterial Agents
Sulfanilamide and Other Sulfonamides Target Specific
Metabolic Reactions

•Sulfonamides out compete essential folic acid components

for binding sites in a bacterial enzyme

•They prevent nucleic acid synthesis and DNA replication

Other Synthetic Antimicrobials Have Additional Bacterial Cell
Targets

•Isoniazid interferes with cell wall synthesis in species of

Mycobacterium

•Quinolones block DNA synthesis in bacteria

The Beta-Lactam Family of Antibiotics
Penicillin Has Remained the Most Widely Used Antibiotic

•Penicillins are active against many gram-positive and

some gram-negative bacteria

•They interfere with cell wall synthesis, causing the cell to

burst
•Some individuals experience an anaphylactic allergic reaction

•Many penicillin-resistant species produce beta-lactamases

that inactivate penicillin

•Numerous semisynthetic penicillins have been developed

Other Beta-Lactam Antibiotics Also Inhibit Cell Wall Synthesis

•Cephalosporins are broader spectrum alternatives to

penicillins

•Monobactams are active against aerobic, gram-negative rods

•Carbapenems are broad spectum drugs

•For example, Imipenem
Other Bacterially-Produced Antibiotics
Vancomycin Also Inhibits Cell Wall Synthesis

•It is effective against gram-positive bacteria such as

staphylococci

•Side effects include damage to the ears and kidneys

Polypeptide Antibiotics Affect the Cell Membrane

•Bacitracin interferes with transport of cell wall precursors

through the membrane

•It is toxic internally, so is used topically

•Polymyxins increase membrane permeability of gram-

negative rods
Many Antibiotics Affect Protein Synthesis

•Aminoglycosides attach to bacterial ribosomes, blocking translation

•Streptomycin is sometimes used in tuberculosis cases

•Gentamicin is used against gram-negative infections in the

urinary tract

•Neomycin is used for intestinal infections and as an ointment

•Kanamycin is used against gram-negative bacteria in wound
tissue
Chloramphenicol is used against a wise variety of bacteria
and some rickettsiae and fungi

It is reserved for serious infections like:

•meningitis
•cholera
•typhoid and typhus fevers
•Rocky Mountain spotted fever

Severe side effects include aplastic anemia and gray

syndrome
Tetracyclines have a similar antimicrobial range to
chloramphenicol

•They have a benzene ring formation

•They can destroy intestinal microbiota and cause staining

of the teeth
Some Antibiotics Inhibit Nucleic Acid Synthesis

•Rifampin interferes with RNA synthesis

•It is effective against tuberculosis, leprosy, and

meningitis

•It can cause liver damage

Targets for antibacterial agents
Antibiotic Assays and Resistance
The agar disk diffusion method involves different antibiotics
diffusing from paper disks in a bacterial colony
There Are Four Mechanisms of Antibiotic Resistance

Many species of bacteria have evolved resistance to certain

antibiotics and synthetic agents
The evolution of strains of S. aureus resistant to multiple drugs is
particularly alarming

1. Resistance to sulfonamides may develop if the bacterial

enzyme changes or if the bacteria evolves an alternate
metabolic pathway

3. Bacteria may evolve the ability to enzymatically inactivate an

antibiotic

5. Bacteria may evolve the ability to prevent drug entry into the
cytoplasm or to pump the drug out of the cytoplasm

7. Bacteria can evolve changes in drug targets like ribosomes

or enzymes involved in replication
Antibiotic Resistance Is of Grave Concern in the Medical
Community

Improper or excessive use of antibiotics causes antibiotic

resistance
•Unnecessarily large antibiotic doses allow resistant strains to
overgrow susceptible ones

•If resistant strains spread to other patients, a superinfection

occurs

•Antibiotics are available over the counter in developing

countries, allowing for overuse and incorrect use

•Antibiotic use is widespread in livestock feeds

•They can be transmitted to humans through meat

consumption

•Bacterial cells can pass resistance genes to other bacterial

cells
New Approaches to Antibiotic Therapy Are Needed

Scientists work to find new antibiotic targets in pathogens

The lipopolysaccharide in gram-negative membranes

contains several possible targets

Interference with DNA adenine methylase disables:

•DNA structure
•replication
•repair

Discovery of new and unique antibiotics is necessary

End of Chapter 24