University of Baghdad

College of Medicine
2022-2023

Title: Antimicrobial agents

Grade: 3rd
Module: ID
Speaker: Assistant Professor :Yasmeen Albayaa
 University of Baghdad/ College of Medicine 2022-2023

Introduction: ‫كلشي يكنل الن مو سيلكتيف‬

• Drugs have been used for the treatment of infectious

diseases since the 17th century (eg, quinine for malaria);
however, antimicrobial chemotherapy as a science began
in the first decade of the 20th century with understanding
of the principles of : selective toxicity, the specific
chemical relationships between microbial pathogens and
drugs, the development of drug resistance, and the role of
combined therapy.
 University of Baghdad/ College of Medicine 2022-2023

• The current era of antimicrobial chemotherapy began in 1935 with the

discovery of the sulfonamides. In 1940, it was demonstrated that
penicillin, discovered in 1929, could be an effective therapeutic
substance. During the next 25 years, research on chemotherapeutic
agents centered largely around substances of microbial origin called
antibiotics. The isolation, concentration, purification, and mass
production of penicillin were followed by the development of
streptomycin, tetracyclines, chloramphenicol, and many other agents.
These substances were originally isolated from filtrates of media in
which their respective molds had grown. Synthetic modification of
previously described drugs has been prominent in the development of
new antimicrobial agents.
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-Mechanisms of Action of Antimicrobial Drugs:

• Antimicrobial drugs act in one of several ways: by selective toxicity, by inhibition of cell membrane
synthesis and function, by inhibition of protein synthesis, or by inhibition of nucleic acid synthesis.

• -Selective Toxicity:
• An ideal antimicrobial agent exhibits selective toxicity, which means that the drug is harmful to a pathogen
without being harmful to the host. Selective toxicity may be a function of a specific receptor required for drug
attachment, or it may depend on the inhibition of biochemical events essential to the pathogen but not to the host.

• -The mechanisms of action of antimicrobial drugs can be discussed under four headings:
1. Inhibition of cell wall synthesis.
2. Inhibition of cell membrane function.
3. Inhibition of protein synthesis (ie, inhibition of translation and transcription of genetic material).
4. Inhibition of nucleic acid synthesis.
 Peptidoglycan layer

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Inhibition of Cell Wall Synthesis:

Inhibition of cell wall synthesis
And chalymedia
• Bacteria have a rigid outer layer (cell wall). The cell wall maintains the shape and
size of the microorganism, which has a high internal osmotic pressure. Injury to the
cell wall (eg, by lysozyme) or inhibition of its formation may lead to lysis of the
cell.
‫يعني دمروا غالفها وحطوها بمحلول مقارب مللوحتها علمود متدمر‬

• In a hypertonic environment (eg, 20% sucrose), damaged cell wall formation

leads to formation of spherical bacterial "protoplasts" from gram-positive
organisms or "spheroplasts" from gram-negative organisms; these forms are
limited by the fragile cytoplasmic membrane. If such protoplasts or spheroplasts
are placed in an environment of ordinary tonicity, they take up fluid rapidly, swell,
and may explode. Specimens from patients being treated with cell wall-active
antibiotics often show swollen or misshapen bacteria.
• Example: All -lactam drugs (pencillin, cephalosporins, carbapenems etc.) are
selective inhibitors of bacterial cell wall synthesis and therefore active against
growing bacteria.
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Inhibition of Cell Membrane Function:

• The cytoplasm of all living cells is bounded by the cytoplasmic membrane,

which serves as a selective permeability barrier, carries out active transport
functions, and thus controls the internal composition of the cell. If the functional
integrity of the cytoplasmic membrane is disrupted, macromolecules and ions
escape from the cell, and cell damage or death ensues. The cytoplasmic membrane
of bacteria and fungi has a structure different from that of animal cells and can be
more readily disrupted by certain agents. Consequently, selective chemotherapy is
possible.
• Examples of agents acting by inhibition of cell membrane function are
amphotericin B, colistin, and the imidazoles ,triazoles and Detergents
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Inhibition of Protein Synthesis:

• It is established that erythromycins, lincomycins, tetracyclines,

aminoglycosides, and chloramphenicol can inhibit protein synthesis in
bacteria. The precise mechanisms of action are not fully established for
these drugs.
• Bacteria have 70S ribosomes, whereas mammalian cells have 80S
ribosomes. The subunits of each type of ribosome, their chemical
composition, and their functional specificities are sufficiently different to
explain why antimicrobial drugs can inhibit protein synthesis in bacterial
ribosomes without having a major effect on mammalian ribosomes.
• In normal microbial protein synthesis, the mRNA message is
simultaneously "read" by several ribosomes that are strung out along the
mRNA strand. These are called polysomes.
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Inhibition of Nucleic Acid Synthesis:

Levofloxacine Combination =trimethoprim-sulfamethaxocole

• Examples of drugs acting by inhibition of nucleic acid synthesis are

the quinolones, pyrimethamine, rifampin, sulfonamides,
trimethoprim, and trimetrexate. Rifampin inhibits bacterial growth by
binding strongly to the DNA-dependent RNA polymerase of bacteria.
Thus, it inhibits bacterial RNA synthesis. Rifampin resistance results
from a change in RNA polymerase due to a chromosomal mutation
that occurs with high frequency. The mechanism of rifampin action
on viruses is different. It blocks a late stage in the assembly of
poxviruses.
• All quinolones and fluoroquinolones inhibit microbial DNA
synthesis by blocking DNA gyrase.
 Resistance to Antimicrobial Drugs: There are many different University of Baghdad/ College of Medicine 2022-2023

mechanisms by which microorganisms might exhibit resistance

to drugs:
(1) Microorganisms produce enzymes that destroy the active drug. Examples:
Staphylococci resistant to penicillin G produce a -lactamase that destroys the
drug. Other -lactamases are produced by gram-negative rods. Gram-negative
bacteria resistant to aminoglycosides (by virtue of a plasmid) produce several
enzymes that destroy the drug.
Tetracycline /prevent attachemnt of
anticodon brough by trna to the A site of the
• (2) Microorganisms change their permeability to the drug. Examples:
ribosome
Tetracyclines accumulate in susceptible bacteria but not in resistant bacteria.
Resistance to polymyxins is also associated with a change in permeability to the
drugs. Streptococci have a natural permeability barrier to aminoglycosides. This
can be partly overcome by the simultaneous presence of a cell wall-active drug, eg,
a penicillin. Resistance to amikacin and to some other aminoglycosides may
depend on a lack of permeability to the drugs, apparently due to an outer
membrane change that impairs active transport into the cell.
 Paraaminobensoic acid

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‫هنا يمنع التطويل‬

‫يمنع التطويل‬ ‫كذلك لكن الفرق انه يمنع حركة الرايبوسوم علمود‬
trna‫يروح للكودون لالخ ويتقبل انتي كودون من ال‬
‫بينما الكلورامفينيكول يمنع تكون ببتيد بوند اصال‬

• 3) Microorganisms develop an altered structural target for the drug. Examples:

Erythromycin-resistant organisms have an altered receptor on the 50S subunit of the
ribosome, resulting from methylation of a 23S ribosomal RNA. Resistance to some
penicillins and cephalosporins may be a function of the loss or alteration of penicillin
binding proteins (PBPs). Penicillin resistance in Streptococcus pneumoniae and enterococci
is due to altered PBPs.
• (4) Microorganisms develop an altered metabolic pathway that bypasses the reaction
inhibited by the drug. Example: Some sulfonamide-resistant bacteria do not require
extracellular PABA (a vitamin like substance and a growth factor required by a several
type of microorganism that is used in the synthesis of folic acid) but, like mammalian cells,
can utilize preformed folic acid.
• (5) Microorganisms develop an altered enzyme that can still perform its metabolic
function but is much less affected by the drug. Example: In trimethoprim-resistant
bacteria, the dihydrofolic acid reductase is inhibited far less efficiently than in
trimethoprim-susceptible bacteria.
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Susceptibility Tests:

• Laboratory tests for antibiotic susceptibility are indicated in

the following circumstances:
• (1) when the microorganism recovered is of a type that is
often resistant to antimicrobial drugs (eg, gram-negative
enteric bacteria); (2) when an infectious process is likely to be
fatal unless treated specifically (eg, meningitis, septicemia);
and (3) in certain infections where eradication of the infectious
organisms requires the use of drugs that are rapidly
bactericidal, not merely bacteriostatic (eg, infective
endocarditis).
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•Thank you