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1. M.Sc Microbiology
Antibiotics

2. Antibiosis is a biological
interaction between two or
more organisms that is
detrimental to at least one
of them; it can also be an
antagonistic association
between an organism and
the metabolic substances
produced by another.
ANTIBIOSIS
Example: zwittermicin A production by B. cereus against
Phytophthora root rot in alfalfa

3. ANTIMICROBIAL AGENT
Any chemical or drug used to treat an
infectious disease, either by inhibiting or
killing the pathogens in vivo

4. ANTIMICROBIAL AGENT
Ideal Qualities:
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

5. ANTIBIOTICS
Substances derived from a microorganism or
produced synthetically, that destroys or limits
the growth of a living organism

6. ANTIBIOTICS – Sources
1. Natural
a.Fungi – penicillin, griseofulvin
b.Bacteria – Bacillus sp. (polymixin,
bacitracin) ; Actinomycetes
(tetracycline, chloramphenicol,
streptomycin)
2. Synthetic

7. ANTIBIOTICS – Classification
I. According to antimicrobial activity
1. Bactericidal
2. Bacteriostatic
II. According to bacterial spectrum of
activity
1. Narrow spectrum
2. Broad spectrum

8. ANTIBIOTICS – Classification
III. According to absorbability from the site
of administration to attain significant
concentration for the treatment of
systemic infection
1. Locally acting
2. Systemic

9. ANTIBIOTICS – Classification
IV.According to mechanism of action
1. Inhibit bacterial cell wall synthesis
2. Alter the function and permeability
of the cell membrane
3. Inhibit protein synthesis (translation
and transcription)
4. Inhibit nucleic acid synthesis

10. ANTIBIOSIS

12. Inhibition of cell wall synthesis
Target: block peptidoglycan (murein) synthesis
Peptidoglycan
 Polysaccharide (repeating disaccharides of N-
acetylglucosamine and N-acetylmuramic acid)
+ cross-linked pentapeptide
 Pentapeptide with terminal D-alanyl-D-alanine
unit required for cross-linking
 Peptide cross-link formed between the free
amine of the amino acid in the 3rd position of
the peptide & the D-alanine in the 4th position
of another chain

13. Inhibition of cell wall synthesis
 -lactam antibiotics
▪ inhibit transpeptidation reaction (3rd stage)
to block peptidoglycan synthesis involves
loss of a D-alanine from the pentapeptide
▪ Steps:
a) binding of drug to PBPs
b) activation of autolytic enzymes
(murein hydrolases) in the cell wall
c) degradation of peptidoglycan
d) lysis of bacterial cell

14. Inhibition of cell wall synthesis
 -lactam antibiotics
Penicillin binding proteins (PBPs)
 enzymes responsible for:
a. cross-linking (transpeptidase)
b. elongation (carboxypeptidase)
c. autolysis

15. Inhibition of cell wall synthesis
 -lactam antibiotics
Lysis of bacterial cell
o Isotonic environment cell swelling
rupture of bacterial cell
o Hypertonic environment – microbes change
to protoplasts (gram +) or spheroplasts
(gram -) covered by cell membrane swell
and rupture if placed in isotonic environment

16. Inhibition of cell wall synthesis
 -lactam antibiotics
o intact ring structure essential for
antibacterial activity
o inhibition of transpeptidation enzyme due
to structural similarity of drugs (penicillin
and cephalosporin) to acyl-D-alanyl-D-
alanine

17. Inhibition of cell wall synthesis
 -lactam antibiotics
PENICILLIN
: Penicillium spp (molds)
final cross-linking step
o active site of the transpeptidase &
 Source
 inhibit
 bind t
inhibit
 bacteri
its activity
cidal but kills only when bacteria
ively growing
are act
 inactivated by -lactamases

18. Inhibition of cell wall synthesis
 -lactam antibiotics
CEPHALOSPORINS
 similar structure and mechanism of action
as penicillin
 most are products of molds of the genus
Cephalosporium

19. Inhibition of cell wall synthesis
B.Other -lactam antibiotics
CARBAPENEMS
 structurally different from penicillin and
cephalosporin
 Imipenem
 with widest spectrum of activity of the
-lactam drugs
 Bactericidal vs. many gram (+), gram
(-) and anaerobic bacteria
 not inactivated by -lactamases

20. Inhibition of cell wall synthesis
A. Other -lactam antibiotics
MONOBACTAMS (Aztreonam)
y vs. gram negative rods
in patients hypersensitive to
 activit
 useful
penicillin

21. Inhibition of cell wall synthesis
C. Other Cell Wall Inhibitors
 Inhibit precursor for bacterial cell wall synthesis
VANCOMYCIN
 Source: Streptomyces orientalis
 Inhibit 2nd stage of peptidoglycan synthesis
by:
a. binding directly to D-alanyl-D-alanine 
block transpeptidase binding
b. inhibiting bacterial transglycosylase
 S. aureus & S. epidermidis infection
resistant to penicillinase-resistant PEN

22. Inhibition of cell wall synthesis
C. Other Cell Wall Inhibitors
CYCLOSERINE
 Inhibit 2 enzymes  D-alanine-D-alanine
synthetase and alanine racemase 
catalyze cell wall synthesis
 inhibit 1st stage of peptidoglycan synthesis
 structural analogue of D-alanine  inhibit
synthesis of D-alanyl-D-alanine dipeptide
 second line drug in the treatment of TB

23. Inhibition of cell wall synthesis
C. Other Cell Wall Inhibitors
ISONIAZID & ETHIONAMIDE
 Isonicotinic acid hydrazine (INH)
 Inhibit mycolic acid synthesis
ETHAMBUTOL
 Interferes with synthesis of arabinogalactan
in the cell wall

24. Inhibition of cell wall synthesis
C. Other Cell Wall Inhibitors
BACITRACIN
 Source: Bacillus licheniformis
 Prevent dephosphorylation of the
phospholipid that carries the peptidoglycan
subunit across the membrane  block
regeneration of the lipid carrier & inhibit cell
wall synthesis
 Too toxic for systemic use  treatment of
superficial skin infections

25. Inhibition of cell membrane function
A. POLYMYXINS
 Source: Bacillus polymyxa
 With positively charged free amino group
"act like a cationic detergent“ interact
with lipopolysaccharides & phospholipid
in outer membrane increased cell
permeability
 Activity: gram negative rods, especially
Pseudomonas aeruginosa

26. Inhibition of cell membrane function
B. POLYENES (Anti-fungal)
 Require binding to a sterol (ergosterol)
change permeability of fungal cell
membrane
AMPHOTERICIN B
 Preferentially binds to ergosterol
 With series of 7 unsaturated double bonds
rolide ring structure
in mac
 Activity: disseminated mycoses

27. Inhibition of cell membrane function
B.POLYENES (Anti-fungal)
NYSTATIN
 Structural analogue of amphotericin B
 Topical vs. Candida
C. AZOLES (Anti-fungal)
 Block cytP450-dependent demethylation of
lanosterol  inhibit ergosterol synthesis
 Ketoconazole, Fluconazole, Itraconazole,
Miconazole, Clotrimazole

28. Inhibition of protein synthesis
 Binds the ribosomes  result in:
1. Failure to initiate protein synthesis
2. No elongation of protein
3. Misreading of tRNA-deformed protein

29. Inhibition of protein synthesis
A. Drugs that act on the 30S subunit
AMINOGLYCOSIDES (Streptomycin)
 Mechanism of bacterial killing involves the ff.
steps:
1. Attachment to a specific receptor protein (e.g. P
12 for Streptomycin)
2. Blockage of activity of initiation complex of
peptide formation (mRNA + formylmethionine +
tRNA)
3. Misreading of mRNA on recognition region 
wrong amino acid inserted into the peptide

30. Inhibition of protein synthesis
A. Drugs that act on the 30S subunit
TETRACYCLINES
 Source: Streptomyces rimosus
 Bacteriostatic vs. gram (+) and gram (-)
bacteria, mycoplasmas, Chlamydiae &
Rickettsiae
 Block the aminoacyl transfer RNA from entering
the acceptor site  prevent introduction of new
amino acid to nascent peptide chain

31. Inhibition of protein synthesis
A. Drugs that act on the 30S subunit
OXAZOLIDINONES (LINEZOLID)
 interfere with formation of
initiation complex  block initiation
of protein synthesis
 Activity: Vancomycin-resistant Enterococci,
Methicillin-resistant S. aureus (MRSA)
& S. epidermidis and Penicillin-resistant
Pneumococci

32. Inhibition of protein synthesis
B. Drugs that act on the 50S subunit
CHLORAMPHENICOL
 Inhibit peptidyltransferase  prevent
synthesis of new peptide bonds
 Mainly bacteriostatic; DOC for
treatment of typhoid fever

33. Inhibition of protein synthesis
B. Drugs that act on the 50S subunit
MACROLIDES (Erythromycin, Azithromycin &
Clarithromycin)
Binding site: 23S rRNA

 Mechanism:
1. Interfere with formation of initiation complexes
for peptide chain synthesis
2. Interfere with aminoacyl translocation reactions
prevent release of uncharged tRNA from
donor site after peptide bond is formed
(Erytnromycin)

34. Inhibition of protein synthesis
B. Drugs that act on the 50S subunit
LINCOSAMIDES (Clindamycin)
 Source: Streptomyces lincolnensis
 resembles macrolides in binding site, anti-
bacterial activity and mode of action
 Bacteriostatic vs. anaerobes, gram + bacteria
(C. perfringens) and gram – bacteria
(Bacteroides fragilis)

35. Inhibition of protein synthesis
C. Drugs that act on both the 30S and 50 subunit
GENTAMICIN, TOBRAMYCIN, NETILMICIN
 Treatment of systemic infections by susceptible
gram (-) bacteria including Enterobacteriaceae &
Pseudomonas
AMIKACIN
 Treatment of infection by gram (-) bacteria
resistant to other aminoglycosides
KANAMYCIN
 vity vs. gram (-) bacteria except
Broad acti
Pseudomonas

36. Inhibition of nucleic acid synthesis
A. Inhibition of precursor synthesis
 Inhibit synthesis of essential metabolites
for synthesis of nucleic acid
SULFONAMIDES
 Structure analogue of PABA (precursor of
tetrahydrofolate)  inhibit tetrahydrofolate 
methyl donor in synthesis of A, G and T
 Bacteriostatic vs. bacterial diseases (UTI, otitis
media 20 to S. pneumoniae or H. influenzae,
Shigellosis, etc.)
 DOC for Toxoplasmosis & Pneumocystis
pneumonia

37. Inhibition of nucleic acid synthesis
A. Inhibition of precursor synthesis
TRIMETHOPRIM
 Inhibit dihydrofolate reductase (reduce dihydrofolic
to tetrahydrofolic acid)  inhibit purine synthesis
TRIMETHOPRIM + SULFAMETHOXAZOLE
 Produce sequential blocking  marked synergism
of activity
 Bacterial mutants resistant to one drug will be
inhibited by the other

38. Inhibition of nucleic acid synthesis
B. Inhibition of DNA synthesis
QUINOLONES
 Inhibit  subunit of DNA gyrase  (+)
supercoiling  (-) DNA synthesis
 Bactericidal; not recommended for children &
pregnant women since damages growing
cartilage
 Fluoroquinolones (Ciprofloxacin),
Norfloxacin, Ofloxacin, etc.

39. Inhibition of nucleic acid synthesis
B. Inhibition of DNA synthesis
NOVOBIOCIN
 Inhibit  subunit of DNA gyrase
FLUCYTOSINE (Anti-fungal)
 Nucleoside analogue  inhibit thymidylate
synthetase  limit supply of thymidine

40. Inhibition of nucleic acid synthesis
B. Inhibition of DNA synthesis
METRONIDAZOLE
 Anti-protozoal; anaerobic infections
 Antimicrobial property due to reduction of its
nitro group by bacterial nitroreductase  (+)
production of cytotoxic compounds  disrupt
host DNA

41. Inhibition of nucleic acid synthesis
C. Inhibit RNA synthesis
RIFAMPICIN
 Semisynthetic derivative of rifamycin B
(produced by Streptomyces
mediterranei)
 Binds to DNA-dependent RNA polymerase
block initiation of bacterial RNA
synthesis
 Bactericidal vs. M. tuberculosis and aerobic
gram (+) cocci