Antibiotic resistance in bacteria is a global threat of 21st century. Here is a brief discussion of Antimicrobial resistance or Drug resistance disease. If you want to study via video lecture on this visit on my YouTube channel : Microbiology WISDOM: Here you can find further more such interesting topics.

1. Presented by:
Neha kausar Nasim Sheikh
M.Sc. Final (Microbiology)
RTMNU
Antibiotic Resistance
in
Bacteria

2. Content
▪ Introduction to Antibiotics and Antibiotic Resistance.
▪ Types of Antibiotic Resistance.
▪ Mechanism of Antibiotic resistance.
▪ Factors contributingAntibiotic Resistance.

3. Antibiotics?
• Medicines used to prevent and treat bacterial infections.
• Antibiotics are one of our most powerful DRUGS for fighting against life-
threatening bacterial infections.
• Anti- against ; Biotic-living organisms.
• Antibiotics are derived from a mould or bacterium or produced synthetically.

4. Antibiotics are of two types…
ANTIBIOTICS
Bactericidal
Eg:Aminoglycerides,beta
lactums,
vancomycin,Quinolones,R
imfapin,Metronidazole.
Bacteriostatic
Eg: Chloramphenicol,
Macrolides, Clindamycin,
tetracyclines.

5. Antibiotic Resistance?
Occur when an
antibiotic has lost its
ability to effectively
control or the
bacterial growth.
1940s to 1962 is the
golden era of
antibiotics.
History
With the discovery of antimicrobials
in 1940s, scientist prophesied the
defeat of infectious disease that had
plagued human kind throughout the
history.
Then the remarkable healing power
of antibiotics invites widespread and
often inappropriate use.
Misuse and Overuse

6. Longer hospital stays
Higher medical cost
Increased mortality rate
 Some organisms have developed resistance
to multiple antibiotics and are called as Multi
Drug Resistant (MDR) pathogens.
 Common MDR organisms are usually
bacteria.
o Vancomycin - Resistant enterococci (VRE)
o Methicillin - Resistant Staphylococcus
aureus (MRSA)

7. Why studying Antimicrobial resistance is
important?
• Serious and growing phenomenon in contemporary medicine.
• Emerged as one of the common public health concern of 21st century.
• Worldwide 700,000 people die each year due to Antibiotic resistance-disease,
according toWHO.
• Antibiotic resistance also complicate the care of many Covid-19
patients.i.e.bactria like streptococcus pneumonia complicate viral infections like
flu,H1N1 and Covid-19.
• Early data from china and recent report suggest that a significant percentage
of hospitalized patients are developing secondary bacterial infections.

8. Types of Antibiotic Resistance.
Antibioticresistance
Intrinsic
Acquired
• In this type of resistance
Bacteria may be inherently
resistant to an antibiotic.
• Gene responsible for this
resistance is call as…
Environmental
resistome
• It occurs when a bacterium
acquires the ability to resist
the action of particular
antibiotic.
 Horizontal gene transfer
(Eg:Transformation,Transduction,
Conjugation)
 Spontaneous mutation.

9. Examples of Natural resistance:
▪ Streptomyces have some genes which are
responsible for resistance to its own
antibiotic.
▪ Gram –ve bacteria have an outer membrane
as a permeability barrier against antibiotic
i.e. Penicillin.
▪ Organism lacks a transport system for
antibiotic.
▪ Efflux pumps
▪ Lacks the target (i.e. NH mycolic acid
synthesis) of antibiotic.

10. Development of
Antibiotic Resistance.
Bacterial cells
that had develop
resistance are
not killed off.
They continue to
divide.
Resulting in a
completely
resistant
population.
Mutation and evolutionary pressure cause
rapid increase in resistance to antibiotics.

11. Acquired resistance can
occur as a result of ….
 Horizontal gene transfer
(Transformation,
Transduction , Conjugation)
 Vertical evolution
( Spontaneous
Mutation)
A] Horizontal gene transfer:
I. Horizontally transfer a gene between organisms.
II. Involves bacteriophages, plasmids and transposons.
III. Genes that are responsible for antibiotic resistance in one
species of bacteria can be transferred to another through
various mechanisms.
B]Vertical evolution / Spontaneous mutation:
I. Spontaneous mutation occur at relatively low rate.
II. Such mutations have deep effects on resistance of
bacterial population to antimicrobial drug.
Acquired Antibiotic Resistance.

12. A] Horizontal gene transfer Examples
Transformation Transduction Conjugation

13. B]Vertical evolution / Spontaneous mutation Examples
Antibiotic resistance to Aminoglycoside streptomycin.
 Result from a single base pair change in the gene encoding
ribosomal protein to which streptomycin binds; the point
mutation alters the target and make drug inactive.
 However, the chance of an organism to develop mutational
resistance to multiple drug is extremely low.

14. Mechanism of Antibiotic Resistance
Efflux
pumping of
antibiotic.
Change in
shape of
receptor.
Inactivation
of
antibiotic.
Alteration
of
pathway.
Modification
of antibiotic
target.
Decreased
uptake of
drug.

15. A] Inactivation of Antibiotic:
• Inactivation involves enzymatic breakdown of
antibiotic molecules.
• E.g.1. Beta-lactumase enzyme:
Beta-
LactamaseSecreted into
bacterial peri-
plasmic
space.
Attacks the
antibiotic as
it reaches to
target.
Bacterial gene
AmpC codes
for Beta
lactamase.
More than
190 forms of
Beta-
lactamase.
TurnedOFF
and only
TurnedON in
presence of B-
lactam ring.
E.g.2. Aminoglycosidase enzyme:
InactivatesAminoglycoside antibiotic before
binding to 30s subunit of ribosome.

16. B] Change in shape of receptor:
• In this type of mechanism mutation takes place in bacterial
cell which alter the drug receptor, so that the drug cannot
enter the cell.

17. C] Efflux pumping of antibiotic:
Found in plasma membrane of
all bacteria and outer membrane
of Gram -ve bacteria.
Keeps the concentration of
antibiotic in the cell below levels
that would destroy the cell.
Efflux
pump?
They are active against:
• Beta lactams
• Fluoroquinolones
• Tetracycline.
TwoTypes of Efflux pumps:
• Narrow spectrum(single type
of Antibiotic.)
• Broad spectrum(More than one
type of Antibiotic).
• Antibiotic is pumped out.
• Cations are pumped in at the same time
• Also used to remove antiseptic and
disinfectant substances.
• No simultaneous import of cation.
• Relatively rare.
Uses
counter
flow.

18. D] Alteration of a pathway:
• Some drug competitively inhibit metabolic pathway of
bacteria .
• To overcome this problem bacteria uses alternative
pathway that produce the required product.

19. E] Modification of Antibiotic Target:
• Bacteria can modify the antibiotic’s target to escape its activity.
• Bacteria must change structure of target but the modified
target must still be able to function.
• This can be achieved in two ways:
Mutation of genes coding for target protein.
Importing a gene that codes for modified target.

20. RIBOSOME
• Resistance can be the
result of modification
of ribosomal RNA so
its no longer
sensitive.
• Some organisms use
target modification in
conjunction with
efflux pumps.
PenicillinBindingProtein(PBPs)
• Present in plasma
membrane.
• PBPs are target for
penicillin.
• As penicillin reach to
bind these proteins
they modified their
structure.
• Therefore there is no
binding to any
penicillin molecule.
• Results in cell wall
constructed correctly
even in presence of
antibiotic.
ENZYME
• Enzymes like:
*DNA gyrase
*Topoisomerase IV
• These enzymes are
target for
Fluroquinolones.
• Structure of DNA
gyrase and
topoisomerase IV is
modified.
• Antibiotics do not
attach the modified
enzyme and bacteria
can continue
reptication even in
presence of the
antibiotics.
PBPs
Enzyme
Modification of Antibiotic Target

21. F] Decreased uptake of Drug:
• Reduce the permeability of membranes to prevent
uptake of drug inside the cell.
They turned off production of porin and
other membrane channel proteins.
How do they
do that?
• This type of mechanism seen in bacterial resistance to
Streptomycin,Tetracycline and Sulfa drugs.

22. Environ
mental
• Huge population.
• Poor sanitization
• Increased
travelling.
Drug
related
• Fake drugs
• Quality of drugs
• Over the counter
availability of action.
• Over usage.
Patient
related
• Poverty.
• Self-medication.
• Lack of sanitization.
• Lack of education.
• Misconception.
Factors
contributing
Antibiotic
Resistance.
Physician
related
• Inadequate dosing
• Lack of current
knowledge and
training.

23. Thank you.