Figure Reference:
Microbiology with
Diseases by Taxonomy
2013 John Wiley & Sons, Inc. All rights
reserved.
BIOM 1005/1905
Dr. Shivanthi Samarasinghe
Learning outcomes:
Learn about range of antimicrobial
and antibiotics.
Able to discuss the mode of
mechanism of action of antimicrobials.
Able to comment on the
mechanism of resistance.
Antimicrobial drugs:
Antimicrobial drugs: drugs that treat
infections
They are often administered internally.
They exhibit selective toxicity.
They may be highly effective at eliminating
one class of microbes (e.g., bacteria), while
ineffective at eliminating others.
They may be of natural origin or
chemically synthesized.
Staphylococcus
aureus
(bacterium)
Penicillium
chrysogenum
(fungus)
Zone where
bacterial growth
is inhibited
sensitive to
the antibiotic;
Bacteria
creates
A larger zone
of inhibition.
Semisynthetic;
Chemically altered
Antibiotics, more effective,
long-lasting, or easier to
administer.
Synthetic;
completely synthesized in
a lab.
Figure 10.2
Microbiology with diseases by
Taxonomy
Inhibit ion of
prot ein
syn t h e s i s
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Di s r u p t i o n o f
c yt o p l a s m i c
m em brane
Polymyxins
Polyenes
(antifungal)
Inhibit ion of general
m e t a b o l i c p at h w a ys
Sulfonamides
Trimethoprim
Dapsone
Mechanisms of Antimicrobial
Drugs
Crossbridge
between
NAM
and NAM
Growth
New NAG and NAM subunits are inserted into the wall by
enzymes, allowing the cell to grow. Other enzymes link new
NAM subunits to old NAM subunits with peptide cross-links.
Penicillin G
(natural)
Methicillin
(semisynthetic)
Penic illi ns
Cephalothin
(natural)
Cephalos por ins
Previousl
y formed
cross-link
Growt
h
Beta-lactam interferes with the linking enzymes, and NAM
subunits remain unattached to their neighbors. However,
the cell continues to grow as it adds more NAG and NAM
subunits.
Antifungal drugs
Much more problematic (eukaryotes!)
Very few available drugs , and the few must focus on
Disruption of cell ergosterol (instead of cholesterol in human
cell membranes).
Inhibition of chitin cell wall structures.
Selective inhibition of fungal mitosis difficult!).
Antiviral drugs
Tricky because viruses often use host cell
processes; If you inhibit a host cell process,
toxicity will be HIGH.
Common mechanisms involves Inhibition of
nucleic acid synthesis
Often through nucleoside/nucleotide
analogues (AZT, acyclovir).
Inhibition of virus life cycle steps .
Antimicrobial
drug
resistance
time line:
Drug-sensitive cells
Drug-resistant
mutant
Remainin
g
Populatio
n grows
over time
Exposur
e to
drug
Mo s t c e lls now r es is t a nt
Mechanisms of Resistance
At least seven mechanisms of microbial resistance
Production of enzyme that destroys or
deactivates drug
Slow or prevent entry of drug into the cell
Alter target of drug so it binds less effectively
Alter their own metabolic chemistry
Pump antimicrobial drug out of the cell before it can
act
Bacteria in biofilms can resist antimicrobials
Mycobacterium tuberculosis produces MfpA protein
Penicilli
n
-lactamase
(penicillinase) breaks
this bond
Figure 10.16 Microbiology with Diseases by
Taxonomy
Inactive
penicillin
Useful reading;
Brock Biology of Microorganisms,
Microbiology with Diseases by
Taxonomy on Antibiotics and
antibiotic drug resistance.
Other mechanisms of action of
Antimicrobials;
Steps in Translation/Protein
Synthesis
1
4
PABA
Sulfamethoxazole
Sulfisoxazole
Sulfanilamide
Enzyme
Dihydrofolic
acid
Enzyme
acid (THF)
PABA
Other
substrates
Purine and
pyrimidine
nucleotides
Tetrahydrofolic Enzymes
Enzymes
PABA
Dihydrofolic
acid
Other
substrates
Dihydrofolic acid
not produced
Active site
Enzyme
Role of PA B A in f olic ac id s yn t hes is in b ac t er ia
and pr ot ozoa
Enzyme
Inh ibit ion of f olic ac id s ynt hes is by s ulf ona m i de