Microbiology lec 4

by Shatha M.Ali
• Antibiotic : Is a chemical substance produced by microorganism (natural
products) which has the capacity to inhibit or kill the growth of others.

• They include a range of powerful drugs and are used to treat diseases
caused by bacteria.

• Antibiotics sources

Synthetic Semi- Natural

synthetic

Fungi Bacteria
Antimicrobial Agent Characters
• 1. kill or inhibit the growth of pathogens.

• 2. Cause no damage to the host .

• 3. Cause no allergic reaction to the host .

• 4. Stable when stored in solid or liquid form.

• 5. Remain in specific tissues in the body long enough to be effective.

• 6. Kill the pathogens before they mutate and become resistant to it.
•A-According to antimicrobial activity:
Classification of antibiotics
B- According to Antibacterial spectrum
C- According to antibiotics
mechanism of actions.

1.Inhibition of cell wall synthesis.

2.Inhibition of cytoplasmic membrane function.

3.Inhibition of protein synthesis.

4. Inhibition of nucleic acid synthesis.

5.Competitive inhibition.
1.Inhibition of cell wall synthesis

• Peptidoglycan: Thick layer in Gram positive and Thin layer in Gram

negative.

• The drugs inhibit bacterial cell wall peptidoglycan synthesis in growing

bacteria.
A-Beta lactam antibiotics as
• PENICILLINS : Belong to β-lactam drugs.

• Source: Penicillium spp.

• Mode of action – Inhibit cell wall

synthesis (bind transpeptidase enzyme involved
in cross-linking of peptidoglycans) and lyses it.

• Spectrum: act against (G +ve) aerobes and

anaerobes .Semi-synthetic penicillins are
effective against some (G –ve) bacteria.
 • CEPHALOSPORINS
• Similar structure and mechanism of action as penicillin .

• Source : molds of the genus Cephalosporium.

• The have a low toxicity and a broader spectrum than natural penicillin.

• 1st Generation cephalosporins (G +ve aerobes) .

• 2nd Generation cephalosporins (G +ve & some G –ve) .

• 3rd Generation cephalosporins (G +ve, G –ve, resistance to beta- lactamase,

penetrate BBB) .
 B-non beta lactam
B-Non beta lactam antibiotics as:

Bacitracin
• Source :Bacillus species.
• It highly toxic so used only topically for wounds.

• It is bactericidal for G+ve and Neisseria.

 Vancomycin
• Bactericidal activity.

• Given by injection but used with short duration due to its toxic
side effect on kidneys

• Its not effective against G-ve bacteria because it cannot

penetrate their outer membrane.
 ISONIAZID and ETHAMBUTOL
• is a fixed-dose combination medication used to treat tuberculosis. It is
used along with other antituberculosis medication.

• It is taken by mouth: Inhibit mycolic acid synthesis.

2-Cell membrane inhibitor
• These antibiotics disorganize the structure or inhibit the function of
bacterial membranes.
• Antibacterial polymyxins(B,E) produced by Bacillus polymyxis .
• Polymyxins: Destroy the membrane function of many G-ve
organisms as pseudomonas and serratia.
 Antifungal cell membrane inhibitors as

• 1-Polyenes, Nystatin :Topically used for Candida infections .

• 2-Amphotericin: Treating systemic candidiasis.

• 3-Fluconazole:Active on yeast and other fungi specially used to

prevent candida infection in HIV infected individuals.
3. Inhibition of protein synthesis:
• Binds the ribosomes either in
30S or 50S subunits

• Result in:

• 1. Failure to initiate protein

synthesis

• 2. No elongation of protein

• 3. Misreading of tRNA-
deformed protein(termination )
A-Drugs that act on the 30S subunit
• 1-Aminoglycosides: Ex: streptomycin and
Kanamycin.

• Bind to the bacterial 30S ribosomal subunit.

• By binding to the ribosome, aminoglycosides

inhibit the translocation of tRNA during
translation and leaving the bacterium unable
to synthesize proteins necessary for growth.

• Cross bacterial cell walls lipopolysaccharide

in gram-negative bacteria and cell
membranes, where they are actively
transported. Change permeability of cell
membrane.
• 2-Tetracycline,Doxycycline and
Chlortetracycline

• Source: Streptomyces rimosus

• Bacteriostatic vs. gram (+) and gram (-) bacteria,

mycoplasmas, Chlamydiae & Rickettsiae.

• Low toxicity antibiotics .

• Inhibit the binding of tRNA to the 30S

ribosomal unit.

• Useful in oral pathogens as Actinomyces, and

other periodontal pathogens

• Also useful as mouth wash to minimize

secondary bacterial infections associated with
oral ulcers.
B-Drugs that act on the 50S subunit

• CHLORAMPHENICOL

• Mode of action - Bind to 50s of ribosome ,inhibits peptide bond

formation.

• Spectrum – it is a broad-spectrum antibiotic, and it is effective

against most anaerobic bacteria, Salmonella, meningococci and

Haemophilus influenzae infections.

• Active against Mycoplasma, Chlamydia and Rickettsial

infections is rapidly absorbed into deep tissues.

 Erythromycins
• They inhibit protein synthesis by attachment
to 50S subunit of ribosome leading to
premature termination of peptide chain.

• The resistance to erythromycin result from

an alteration (methylation) of the rRNA
receptor( plasmid controlled).

• Bacteriostatic - inhibit G+ve bacteria,

Mycoplasma, and useful in patients allergic
to penicillin.
• Clarithromycin & Azithromycin against G +ve and G –ve,
bacteria resistant to erythromycin is also resistant to these
drugs.

• Licomycin &Clindamycin:

• Active against anaerobes (ex. Bacteroides ), Gram-positive

bacteria and (Neisseria, H. influenzae).

• They are excellent agents for bone and joint infections caused
by Staphylococci.
4-Inhibition of nucleic acid synthesis
 Inhibition of RNA synthesis
• Rifamycin: Semisynthetic derivative of
rifamycin B (produced by Streptomyces
mediterranei)

• It bind strongly to the enzyme and inhibit

initiation of bacterial RNA synthesis .

• Used for treatment of Mycobacterium

tuberculosis.

• It acts quite specifically on the bacterial

RNA polymerase

• It is inactive towards DNA polymerase

or RNA polymerase from animal cells.
 Inhibition of DNA replication:
• 1-Quinolones and Nalidixic acid: they block the DNA gyrase enzyme and
prevent supercoiling of DNA , useful as urinary antiseptics, oral and injection
uses.
• 2-Fluoroquinolones, Ciprofloxacin, levofloxacin: active
against enterobacteriaceae and bacteria resistant to the3^th
generation cephalosporines as Neisseria, Chlamydia and
Haemophilus.

• 3-Metronidazole:

• Mode of action : it causes DNA damage and inhibit its

replication.

• It is an anti-protozoal drug used for the treatment of

Trichomonas, Giardia and Amebic infections.
5-Antimetabolites(Competitive inhibition)
• Sulfonamides

• Bacteriostatic

• Mode of action: Sulfonamides competitively block the

biosynthesis of tetrahydrofolate (folic acid) which acts as a
carrier of a carbon fragment required for the synthesis of
bacterial DNA, RNA and cell wall proteins.
 Trimethoprim
• Is highly effective inhibitor of the binds to dihydrofolate reductase and inhibits the
formation of tetrahydrofolic acid (THF).

• THF is an essential precursor in the thymidine synthesis pathway and interference

with this pathway inhibits bacterial DNA synthesis.

• Effective for the treatment of urinary tract infection(UTI), also act synergistically
with sulfonamides because they inhibit different steps in the same metabolic
pathway.
Combinations of Antimicrobial Agents
• Antibiotic are-frequently used in combination for the following reasons:-

• 1 . To give prompt treatment to patients suspected of having a serious

microbial infection. Such as :- bacterial meningitis in children.

• 2. To delay the emergence of microbial mutants resistant to one drug in

chronic infections .such as :- tuberculosis

• 3.To treat mixed infections.

• 4. To achieve bactericidal synergism or to provide bactericidal action.

Antimicrobial synergism can occur in
several types
• 1. Two drugs may sequentially block a microbial metabolic pathway .such as
(sulfonamides + trirmethoprim) ,effective against (shigellosis, serratia,
salmonellosis).

• 2. A drug such as cell wall inhibitor (penicillin ,cephalosporin) may enhance

the entry of an aminoglycoside into bacteria such as :-

• penicillin enhance the uptake of gentamicin or streptomycin by enterococci

• penicillin & tobramycin may be synergistic against some strains of

pseudomonas.
• 3. One drug may affect the cell membrane & facilitate the entry of the
second drugs .such as: amphotericin + flucytosine against certain fungi (e.g.
Cryptococcus, Candida).

• 4. One drug may prevent the inactivation of a second drug by microbial

enzymes.

Thus inhibitors of β-lactamase (e.g. clavulanic acid, sulbactam, tazobactam )

can protect Amoxicillin , pipercillin from inactivation by 𝛽 –lactamase.
Mechanisms of Resistance to Antimicrobial Agents

• 1-The organism produces enzymes that destroy the drugs e.g. production of:-
A- β-lactamase - that destroys penicillin .

• B - Acetyl transferase produced by gram negative bacilli destroys

chloramphenicol.

• 2-The organism changes its permeability to the drug, by modification of

protein in the outer cell membranes e.g. resistance to Polymyxins.

• 3-The organism develops an altered receptor site for the drug e.g resistance
to aminoglycosides is associated with alteration of a specific protein in the
30S subunit of the bacterial ribosome that serves as a binding site in
susceptible organisms.