Red azo dye protosil
Era of systemic antibacterial chemotherapy
Protected mice against systemic streptococcal infection and cured patients suffering from the disease.
Protosil is cleaved, releasing p-aminobenzene sulfonamide which has antibacterial activity.
Effective chemotherapy drugs must:
Enter the cell
Bind physically to a cellular structure involved in some process essential for the growth of the cell
Inhibit the process in which that cell structure is involved
The treatment of infectious diseases with chemicals or antibiotics that are inhibitory or lethal of the infecting agents.
The property of some antimicrobial agents to be toxic for a microorganism and nontoxic for the host.
A low-molecular-weight chemical agent produced by one organism that is harmful to other organisms.
Drug prevents the growth of microorganisms. Must be used for a sufficient time to allow host's own defenses, such as phagocytosis and antibodies, to destroy the organisms.
Modes of Action of Antibacterial Agents
Folic Acid synthesis
Protein synthesis (50S and 30S)
Cell Wall acting antibacterial agents
interfere with the synthesis of peptidoglycan
Ultimately undergoes osmotic lysis
Degradation of peptidoglycan occurs during which event:
Binary Fission; inhibition of peptidoglycan affects the daughter cells.
Antibiotics that bind to receptors on 30S
block the binding of fmet-tRNA to the ribosome
Prevent attachment of tRNA to acceptor sites
Cause misreading of codons on mRNA
lead to the formation of non-functional proteins
Antibiotics that bind to receptors on 50S
Chloramphenicol blocks the action of peptidyl transferase
Erythromycin blocks the translocation step
Alteration of Cell Membranes
Especially polypeptide antibiotics, incorporate themselves into and alter bacterial cell membranes. Results in loss of important metabolites from the bacterial cell and cell death.
Inhibition of Nucleic Acid Synthesis
Antibiotics can interfere with DNA replication and RNA transcription in bacterial cells. Mammalian DNA and RNA can be affected as well, thus limiting the use of these drugs.
Inhibit bacterial DNA gyrases or topoisomerases
antimetabolites that compete with p-aminobenzoic acid (PABA), which is the substrate for enzymatic reaction leading to synthesis of folic acid.
DO NOT INTERFERE WITH MAMMALIAN CELL METABOLISM-no folic acid synthsis
Synthesized by p-aminobenzoic acid (PABA)
Vitamin the functions as a coenzyme for the synthesis of the purine and pyrimidine bases of nucleic acids
Nongenetic origin of drug resistance
loss of specific target structures
active replication of bacteria is required
alteration of the structure of the receptor of the drug
permeability of the drug
Resistant factor plasmid
may carry genes for resistance to one and often several antimicrobial drugs and heavy metals.
encode enzymes that degrade the drug or modify the drug
Plasmid encoded proteins can pump (efflux) the drug out of the bacterial cell.
Mechanisms of drug resistance
Bacterium may develop and altered metabolic pathway
Altered structural target for the drug
Production of an enzyme that destroys the drug
A microbe may change its permeability to the drug
Bacterium may be able to pump (efflux) out any antibiotic entering the cell
Bacterium may develop an altered enzyme that still can perform its metabolic function but is less affected
Antibiotic Sensitivity Tests
In vitro; valuable for selecting chemotherapeutic agents active against the infecting organism.
Simply a measurement of the effect of the antimicrobial agent against the organism
Selection of a drug and patients outcome are influenced by:
pharmacokinetic properties of the drug
site of infection
patients general medical status