Resistance to

Antibacterial Agents
 Bacteria Medical
agents

Antibacterial
Small single celled Diseases agents
microorganisms
Germs Bactericidal Bacteriostatic

Kill microbes Inhibit growth

Site of actions

Different Penicillins, Tetracycline,

mechanisms Isoniazid Chloramphenicol
 Inhibiting Protein
synthesis

Inhibiting Cell Inhibiting Nucleic

wall synthesis
Mechanism acid synthesis

of actions
Inhibiting the Injuring the
synthesis of Essential Plasma membrane
metabolites
Inhibiting Cell wall Antibiotics
synthesis
Peptidoglycan

Peptidoglycan layers Penicillin,

Cephalosporins,
Cell lysis Carbapenems
Bacterial Cell
wall Major component of
bacterial cell wall

Inhibiting Protein Antibiotics 80S

70S
synthesis ribosome 60S
ribosome
50S Bacterial
40S Host cells
30S
cells
Chloramphenicol,
Least affected Erythromycin,
Protein
Streptomycin,
synthesis
Tetracyclines
Inhibiting Nucleic DNA
Replication Transcription
acid synthesis
Antibiotics DNA ---> mRNA

DNA RNA
Enzyme involved in
DNA gyrase synthesis synthesis
RNA polymerase transcription

RNA polymerase
Helps with winding and
unwinding of DNA Fluoroquinolones
Rifampin
Injuring the Plasma ↑Permeability Needed for
membrane Loss of important survival of
Polypeptide metabolites bacteria
Antibiotics

Inhibiting the synthesis of Competitive

Essential metabolites Product inhibition
Enzyme Substrate Substrate
ES
Antibiotics Complex

Synthesis of Essential Product

metabolites Enzyme
Folic acid No active site available for
Survival and growth of Inhibitor substrate binding

bacteria
PABA Proteins and
Para-aminobenzoic acid
Competitive (PABA) Folic acid nucleic acid
inhibition Sulfanilamide
 Long exposure to
Resistance to disease

Antibacterial Agents
Antibiotics
Develop
resistance

Newly colonized Local

individuals population
Disease for
Bacteria More susceptible to More resistant to
diseases diseases

Mortality rate Develop resistance

is high against that antibiotic
 Resistance
Resistant
Bacteria multiply
Mutations arise
rapidly
regularly
Resistant genes can
be transferred
Random
rapidly Transformation
mutations

Genetic Conjugation
characteristic
Resistant microbes

Transposons and
intergrons
Resistant progeny
 Transformation Conjugation
Naked DNA
From Cytoplasm Transposons and
cytoplasm
Antibiotic Integrons
resistant gene
Mobile genetic
elements
Non-resistant Or
Sensitive Plasmid
Resistant
Altered gene will Can encode
alter affinity of Resistant
Non-resistant Or antibiotic
Sensitive
product Penicillin resistant genes
binding protein
genes

Now Resistant Resistant Non-resistant Or

Sensitive
PBPs produced
Transposons
Less affinity for
↑ Antibiotic penicillin
resistance Now Resistant
 Multiple Resistance against
more than one
resistance antibacterial agents Antibiotic
degradation

Transmission Impermeability
Transposons and
Integrons
Mechanism of
Already resistant
Conjugation Resistance Efflux
bacteria mechanisms

More
Alternative
exposure
with Alteration of pathway
antibiotics the target site
Multiple resistant
bacteria
 Inactive
Destroy Antibiotic
Enzyme structure
Inactive
β-
lactamase
Enzyme Penicillin
inactivation S. aureus (Destroy β-
lactam ring)
Antibiotic
Degradation
Enzyme Inactive
addition Inactivating
Enzyme chemical group
Antibiotic
Aminoglycosides Acetyl,
Antibiotic Amino,
Adenosine
Inactive group
 Impermeability Efflux
mechanism
Naturally
resistant
Efflux pump
Antibiotic
Cell envelop is
impermeable

Bacterial cell
Antibiotic

Tetracyclines,
E-coli, Macrolides,
Streptococci Fluoroquinolones
β-Lactam
Pseudomonas antibiotics
spp.
Alternative Pathway Alteration of the
Antibiotic
target site

Genetic mutation No action

A—-B—-C--D--Product
X--Y No binding

Target site Altered

Target site

Antibiotic
Methicillin,
Flucloxacillin Target site
S. aureus

Rifampicin β
Genetic
mutation
mec-A gene Penicillin binding
proteins
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