This document discusses antibiotic resistance, defining it as when bacteria are not killed or inhibited by an antimicrobial drug. It outlines five main mechanisms by which bacteria develop resistance: producing enzymes that destroy drugs, changing permeability, altering structural targets, developing alternate metabolic pathways, and altering enzymes. Resistance can originate from genetic mutations or non-genetically when bacteria are inactive. Horizontal transfer of resistant genes between bacteria, especially via plasmids, allows resistance to spread rapidly. Preventing inappropriate antibiotic use and implementing resistance containment policies can help reduce the emergence and spread of resistant bacteria.

1. Antibiotic Resistance
Dr. Md. Abdullah Yusuf
Assistant Professor, Department of Microbiology
National Institute of Neurosciences & Hospital
Dhaka, Bangladesh
Email: ayusuf75@yahoo.com

2. Learning Objectives
• Definition
• Mechanism of Antibiotic Resistance
• Origin of Antibiotic Resistance
• Prevention

3. Definition
• a state when bacteria are not killed or inhibited by a
particular antimicrobial

5. Mechanisms of Antibiotic Resistance
(1) Bacteria produce enzymes that destroy the active
drug
Examples
• Staphylococci produce beta-lactamase
– resistant to penicillin G

6. Mechanisms of Antibiotic Resistance
(2) Bacteria change their permeability to the drug
Examples:
• Resistance to polymyxins associated with
– change in permeability to the drugs.
• Streptococci
– natural permeability barrier to aminoglycosides
• Pseudomonas
– possess impermeable cell membrane prevent
influx of drug

7. Mechanisms of Antibiotic Resistance
(3) Microorganisms develop an altered structural target
for the drug
Examples
• Erythromycin-resistant bacteria have
– altered receptor on the 50S subunit of the
ribosome
• Penicillin resistance in Streptococcus pneumoniae
and enterococci
– due to altered PBPs

8. Mechanisms of Antibiotic Resistance
(4) Microorganisms develop an altered metabolic
pathway that bypasses the reaction inhibited by the
drug
Example
• Some sulfonamide-resistant bacteria do not require
extracellular PABA but
– can utilize preformed folic acid

9. Mechanisms of Antibiotic Resistance
(5) Microorganisms develop an altered enzyme that can
still perform its metabolic function but is much less
affected by the drug
Example
• In trimethoprim-resistant bacteria
– the dihydrofolic acid reductase is inhibited far less
efficiently than in trimethoprim-susceptible bacteria

10. Origin of Drug Resistance
• Non-genetic Origin of Drug Resistance
• Genetic Origin of Drug Resistance
– Chromosomal Resistance
– Extrachromosomal Resistance
• Plasmid mediated Resistance
• Transposon-Mediated Resistance
• chromosomal resistance is less of a clinical
problem than is plasmid-mediated resistance

11. Non-genetic Origin of Drug Resistance
• Active replication of bacteria
– required for most antibacterial drug actions
– metabolically inactive (non-multiplying) bacteria
phenotypically resistant to drugs.
• Example
– Mycobacteria survive in tissues for many years

12. Non-genetic Origin of Drug Resistance
• Microorganisms lose the specific target structure for
a drug for several generations and thus be resistant
• Example
– Penicillin-susceptible bacteria
• change to cell wall-deficient L forms
• resistant to cell wall-inhibitor drugs (penicillins,
cephalosporins)

13. Non-genetic Origin of Drug Resistance
• Microorganisms infect the host at sites where
antimicrobials are excluded or are not active
• Examples
– Aminoglycosides such as gentamicin are not effective
in treating salmonella enteric fevers because the
salmonellae are intracellular and the aminoglycosides
do not enter the cells
– Drugs that enter cells are effective in treating
legionnaires' disease because of the intracellular
location of Legionella pneumophila.

14. Genetic Origin of Drug Resistance
• Chromosomal Resistance
– mutation in the gene that codes for either the
target of the drug or the transport system in the
membrane that controls the uptake of the drug

15. Extrachromosomal Resistance
• Plasmid mediated Resistance
– Resistance plasmids (resistance factors, R factors)
– carry the genes for a variety of enzymes that can
degrade antibiotics and modify membrane
transport systems
• Transposon-Mediated Resistance
– genes that are transferred either within or
between larger pieces of DNA such as the
bacterial chromosome and plasmids

16. Plasmid-mediated resistance
• is very important from a clinical point of view
for three reasons:
– It occurs in many different species, especially
gram-negative rods
– Plasmids frequently mediate resistance to
multiple drugs
– Plasmids have a high rate of transfer from one cell
to another, usually by conjugation.

17. Transfer of Resistance
• Horizontal transfer
– Mutated chromosome passed
– vertically by selection to daughter cells
• Horizontal transfer
– rapidly disseminate resistance by clonal spread of
resistant strain itself or
– by genetic exchange between resistant and
further susceptible strains

18. Horizontal Transfer of Resistance
• More commonly determinant “R” factor from donor
to recipient cell of the same species or often to
another bacterial species
– Transformation
– Transduction
– Conjugation

24. Cross-Resistance
• Microorganisms resistant to a certain drug
– resistant to drugs that share a mechanism of
action
– agents closely related chemically (eg, different
aminoglycosides) or
– similar mode of binding or action (eg, macrolides-
lincomycins)

25. Antibiotic Resistant Bacteria
• MRSA- Methicillin Resistant Staphylococcus aureus
• VISA- Vancomycin Intermediate Staphylococcus
aureus
• VRSA- Vancomycin Resistant Staphylococcus aureus
• ESBL- Extended Spectrum Beta-lactamases
• MDR Gram negative Bacteria- Multidrug Resistant
Gram negative Bacteria
• MDR TB- Multidrug Resistant Tuberculosis
• XDR TB- Extreme Drug Resistant Tuberculosis
• MBL Bacteria- Metalobeta Lactamases Bacteria
• VRE

26. Prevention of Resistance
• Practicing rational use
• Administering by proper dose
• Administering through proper route
• Administering for proper duration
• Selecting proper antibiotic for proper infection
• Implementation of antibiotic policy
• Implementation through one approach

27. Review questions
• What is antibiotics? How do they act
• What is selective toxicity?
• What is drug resistance ?
• State different mechanisms of antibiotic
resistance with example

28. Review questions
• How do bacteria acquire property of
resistance ?
• How do resistance is disseminated among
bacterial population ?
• What steps should be taken to reduce
resistant bactera ?

29. Thank You