This document summarizes the mechanisms of action of various antimicrobial agents. It discusses how antibiotics like penicillins, cephalosporins, vancomycin, and teicoplanin work by inhibiting bacterial cell wall synthesis. It also describes how other antibiotics like aminoglycosides, tetracyclines, macrolides, chloramphenicol, sulfonamides, trimethoprim and quinolones inhibit bacterial protein synthesis or nucleic acid synthesis. The document provides examples of specific antibiotics and explains their mechanisms of action, spectra of activity and importance.

1. MECHANISM OF ACTION OF
ANTIMICROBIAL AGENTS
Reshma Soman
MPhil Biosciences

2. INTRODUCTION
• The chemical and physical agents are used to treat inanimate
objects in order to destroy microorganisms or inhibit their
growth.
• Microorganisms also grow on and within other organisms,
and microbial colonization can lead to disease, disability, and
death.
• Thus the control or destruction of microorganisms residing
within the bodies of humans and other animals is of great
importance.
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4. Introduction
• ANTIBIOTICS: Chemical substance produced by micro
organism that inhibit the growth of other microbes.
• ANTIMICROBIAL AGENTS: Chemical substance or biological
source produced by chemical synthesis that kills or inhibit the
growth of other organism.
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5. General Characteristics of
Antimicrobial Drugs
• A successful chemotherapeutic agent must have selective
toxicity.
• It must kill or inhibit the microbial pathogen while damaging
the host as little as possible.
• The degree of selective toxicity expressed in terms of
therapeutic dose and toxic dose.
• The therapeutic dose, the drug level required for clinical
treatment of a particular infection.
• The toxic dose, the drug level at which the agent becomes too
toxic for the host.
• Therapeutic index: The ratio of toxic dose to therapeutic dose.5

6. Classification Of Antibiotics
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9. Classification Of Antibiotics
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11. ANTIBACTERIAL DRUGS
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12. ANTIBACTERIAL DRUGS
Based on mechanism of action they can be classified into:
1.INHIBITORS OF CELL WALL SYNTHESIS
2. PROTEIN SYNTHESIS INHIBITORS
3.METABOLIC ANTAGONISTS
4.NUCLEIC ACID SYNTHESIS INHIBITORS
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13. 1. INHIBITORS OF
CELLWALL SYNTHESIS
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14. INHIBITORS OF CELLWALL
SYNTHESIS
Selective inhibitors- they target the structure and function not
found in eukaryotic cells.
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15. PENICILLINS
• Most of them are derivatives of 6-amino penicillanic acid. (eg:
penicillin G or benzyl penicillin).
• Crucial feature –beta lactam ring.
• Penicillin resistant bacteria have pencillinase activity.
• Structure of penicillin resembles the terminal D-alanyl-D -
alanine found on the peptide side chain of the peptidoglycan
subunit.
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16. Penicillins
• Structural similarity blocks the enzyme catalyzing the trans-
peptidation reaction that forms the peptidoglycan cross links.
• Penicillin G is effective against bacteria causing gonorrhea and
meningitis.
• Penicillin have broad spectrum activity.
• Ampicillin effective against Gram negative bacteria.
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18. CEPHALOSPORINS
• Isolated in 1948 from the fungus Cephalosporium.
• Contain beta lactam structure that is very similar to penicillin.
• Inhibit the trans-peptidation reaction during peptidoglycan
synthesis.
• They are given to penicillin allergic patients.
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20. VANCOMYCIN
• Glycopeptide antibiotic, produced by bacterium Streptomyces orientalis.
• Cup shaped molecule peptide linked to diasaccharide.
• Peptide portion blocks the trans-peptidation reaction by binding specifically to
D- alanyl – D- alanine in peptidoglycan.
• Bactericidal for Gram positive Staphylococcus, Clostridium, Bacillus,
Streptococcus, Enterococcus.
• Resistance when bacteria change terminal D- alanine to D- lactate or D-serine
thus altering the target.
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21. This is also called the ‘drug of last resort’.
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22. Vancomycin
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23. TECOPLANIN
• Glycopeptide antibiotic.
• Produced by Actinoplanes teichomyceticus.
• It is similar to the structure and action of vancomycin, but
fewer side effects.
• Active against Staphylococci, Enterococci, Streptococci,
Clostridia, Listeria, and many gram positive pathogens.
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24. Tecoplanin
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25. 2. PROTEIN SYNTHESIS
INHIBITORS
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26. PROTEIN SYNTHESIS
INHIBITORS
• Inhibit protein synthesis, binding with bacterial chromosome
and other component of protein synthesis.
• Discriminate between eukaryotic and bacterial ribosomes.
• Therapeutic index is fairly high.
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27. AMINOGLYCOSIDES
• Contain a cyclohexane ring and aminosugars.
• Streptomycin, kanamycin, neomycin and tobramycin
synthesized by different species of Streptomyces, where as
gentamycin from related genus Micromonospora purpura.
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28. Aminoglycosides
• Gentamycin is used to treat Gram negative bacteria - Proteus,
Escherichia, Klebsiella, Serretia infections.
• Aminoglycosides can be quite toxic - cause hearing and renal
damage, loss of balance, nausea and allergic reaction.
• They bind to 30S ribosomal subunit to interfere protein synthesis.
• Binding to incorrect subunit, the aminoglycoside allow the
incorrect amino acid to be brought to ribosomes by tRNA.
• Bactericidal, most effective against Gram negative pathogens.
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29. TETRACYCLINES
• Familiar antibiotic with common four ring structure to which
a variety of side chains are attached.
• Oxytetracyline and chlortetracyclin are produced naturally by
Streptomyces species, whereas others are semi synthetic.
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30. Tetracyclines
• Mechanism of action similar to aminoglycosides.
• Action is only bacteriostatic.
• They are broad spectrum antibiotics - active against many
bacteria including intracellular Rickettsias, Chlamydia, and
Mycoplasma.
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31. MACROLIDS
• Contain ring structure consisting of 12 to 22 carbons called
lactone ring, the lactone ring is linked to one or more sugars.
• Erythromycin binds to 50S subunit to inhibit bacterial protein
synthesis.
• Erythromycin relatively broad spectrum antibiotic - effective
against Gram positive bacteria Mycoplasma and few Gram
negative bacteria.
• Used to patients who are allergic to penicillin and in the
treatment of whooping cough, diptheria, diarrhoea caused by
Campylobacter, and Pneumonia from Legionella or
Mycoplasma infections.
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32. Macrolids
Usually bacteriostatic.
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33. Macrolids
• Clindamycin effective against variety of bacteria including
Staphylococci and anaerobes such as bacteroides.
• Azithromycin active against Chlamydia trachomatis.
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34. CHLORAMPHENICOL
• First produced by Streptomyces venezuelae .
• Like erythromycin ,this antibiotic binds to 50S subunit to inhibit
bacterial protein synthesis.
• It has very broad spectrum activity.
• Quite toxic.
• Used in life threatening situation.
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35. 3.METABOLIC
ANTAGONISTS
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36. 3.METABOLIC ANTAGONISTS
• They antagonize or block the functioning of metabolic
pathway.
• Antimetabolites are structurally similar to the substrates of
key enzymes and compete with the metabolites for binding
site of these enzyme.
• Once bound to the enzyme they block enzyme activity, further
progression of the pathway. They are broad spectrum but
bacteriostatic.
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37. SULFONAMIDES OR SULFA
DRUGS
• Structurally related to sulfanyl amide, an analogue of P-
aminobenzoic acid (PABA).
• PABA important co-factor of many enzymes and needed for folic
acid synthesis.
• Folic acid is a precursor of purins and pyramidines and other
important cell component.
• It competes with PABA for active site of enzyme involved in folic
acid synthesis.
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38. Sulfonamides Or Sulfa Drugs
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39. Sulfonamides Or Sulfa Drugs
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40. Sulfonamides Or Sulfa Drugs
• Causing a decline in folate concentration, resulting purin and
pyramidine concentration leads to ceasation protein synthesis
and DNA replication.
• They are selectively toxic to many bacteria and protozoa because
they manufacture their on folate, cannot effectively take up these
co-factor whereas human do not synthesis folic acid.
• They have high therapeutic index.
• Increasing resistance limit their effectiveness.
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41. TRIMETHOPRIN
• It is a synthetic antibiotic inhibit production of folic acid.
• It does not bind to dehydrofolate reductase (DHFR).
• The enzyme responsible for converting dehydrofolic acid to
tetrahydrofolic acid by competing against the tetra hydro
folic acid substrate.
• It is a broad spectrum antibiotic.
• Often used to treat respiratory tract infections, infections of
middle ear, urinary tract infection and travellor’s diarrhea.
• Combined with sulfa drugs to increase efficacy of treatment
by blocking two key step in folic acid pathway.
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42. 4.NUCLEIC ACID
SYNTHESIS INHIBITION
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43. 4.NUCLEIC ACID SYNTHESIS
INHIBITION
• They in inhibit nucleic acid synthesis function by inhibiting –
1, DNA polymerases and topoisomerases
2, RNA polymerases to block replication or transcription,
respectively.
• The drugs not selectively toxic because bacteria and
eukaryotes do not differ greatly with respect to nucleic acid
synthesis.
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44. QUINOLONES
• Synthetic drug with 4 quinolone ring.
• First quinolone is naldixic acid.
• Currently used fluroquinolones - ciprofloxacin, norfloxacin, and
ofloxacin.
• Quinolones act by inhibiting the bacterial DNA gyrase and
topoisomerase II.
• DNA gyrase introduces negative twist in DNA and helps
separate its strands.
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45. Quinolones
• Inhibition of DNA gyrase disrupts DNA replication and
repair, bacterial chromosome separation during division, and
other cell processes involving DNA.
• Fluoroquinolones also inhibit topoisomerase II.
• Quinolones are bactericidal.
• Quinolones are broad - spectrum antibiotics.
• They are highly effective against enteric bacteria such as
E coli and Klebsiella pneumoniae.
• They can be used with Haemophilus, Neiserria, P aeruginosa,
and other Gram- negative pathogens.
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46. Quinolones
• The quinolones also are active against gram-positive bacteria
such as S. aureus, Streptococcus pyogenes, and
Mycobacterium tuberculosis.
• Quinolones are effective, administered orally but can cause
diverse side effects gastrointestinal upset.
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48. ANTIFUNGAL DRUGS
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49. ANTIFUNGAL DRUGS
• Treatment of fungal infections generally has been less successful
than that of bacterial infections.
• Because eukaryotic fungal cells are much more similar to human
cells than are bacteria.
• Many drugs that inhibit or kill fungi are therefore quite toxic for
humans.
• Most fungi have a detoxification system that modifies many
antifungal agents.
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50. Antifungal Drugs
• Effective antifungal agents frequently either extract membrane
sterols or prevent their synthesis.
• Animal cells do not have cell walls, the enzyme chitin synthase is
the target for fungal-active antibiotics such as polymyxin D and
nikomycin.
• Fungal infections are often subdivided into superficial mycoses
and systemic mycoses.
• Treatment for these two types of disease is very different.
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51. Antifungal Drugs
• Three drugs containing imidazole — miconazole, ketoconazole,
clotrimazole — are broad-spectrum agents.
• They are thought to disrupt fungal membrane permeability and
inhibit sterol synthesis.
• Tolnaftate is used topically for the treatment of cutaneous
infections.
• Nystatin, a polyene antibiotic from Streptomyces, is used to control
Candida infections.
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52. Antifungal Drugs
• It binds to sterols and damages the membrane, leading to fungal
membrane leakage.
• The synthetic oral antimycotic agent 5-flucytosine is effective
against most systemic fungi.
• The drug is converted to 5-fluorouracil by the fungi, incorporated
into RNA in place of uracil, and disrupts RNA function.
• Fluconazole is used in the treatment of candidiasis, cryptococcal
meningitis and coccidioidal meningitis.
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Antifungal Drugs

54. ANTI VIRAL DRUGS
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55. ANTI VIRAL DRUGS
• Viruses enter host cells and make use of host cell enzymes
and constituents.
• A drug that would block virus reproduction also was thought
to be toxic for the host.
• Antiviral drugs disrupt either critical stages in the virus life
cycle or the synthesis of virus-specific nucleic acids.
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56. Anti Viral Drugs
• Amantadine and rimantadine can be used to prevent
influenza A infections.
• Amantadine blocks the penetration and uncoating of
influenza virus particles.
• Adenine arabinoside or vidarabine disrupts the activity of
DNA polymerase and several other enzymes, involved in DNA
and RNA synthesis and function.
• It is given intravenously or applied as an ointment to treat
herpes infections.
• Acyclovir is also used in the treatment of herpes infections. 56

57. Anti Viral Drugs
• Upon phosphorylation, acyclovir resembles deoxy - GTP and
inhibits the virus DNA polymerase.
• Valacycloviris an orally administered prodrug form of acyclovir.
• Ganciclovir, penciclovir, and its oral form famciclovir are effective
in treatment of herpesviruses.
• Foscarnet is an organic analogue of pyrophosphate that binds to
the polymerase active site and blocks the cleavage of
pyrophosphate from nucleoside triphosphate substrates.
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58. Anti Viral Drugs
• It is used in treating herpes and cytomegalovirus infections.
• Several broad-spectrum anti-DNA virus drugs have been
developed.
• The drug HPMPC or cidofovir, is effective against papovaviruses,
adenoviruses, herpesviruses, iridoviruses, and poxviruses.
• The drug acts on the viral DNA polymerase as a competitive
inhibitor and alternative substrate of dCTP.
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59. Anti Viral Drugs
• Anti-HIV drugs first drugs to be developed were reverse
transcriptase inhibitors such as azidothymidine (AZT) or
zidovudine, lamivudine (3TC), didanosine (ddI), zalcitabine (ddC),
and stavudine (d4T).
• These interfere with reverse transcriptase activity and therefore
block HIV reproduction.
• HIV protease inhibitors have also been developed. The most used
are saquinvir, indinavir, and ritonavir.
• Protease inhibitors are effective because HIV, like many viruses,
translates multiple proteins as a single polypeptide. 59

60. Anti Viral Drugs
• Polypeptide must then be cleaved into individual proteins
required for virus replication.
• Protease inhibitors mimic the peptide bond that is normally
attacked by the protease.
• The most publicized antiviral agent has been tamiflu.
• Tamiflu is a neuraminidase Inhibitor.
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