Mechanism of drug resistance

modifications

1. MECHANISM OF DRUG RESISTANCE SUBHANANTHINI JEYAMURUGAN, 18PY17, M.SC., MICROBIOLOGY. AYYA NADAR JANAKI AMMAL COLLEGE SIVAKASI.

2. INTRODUCTION: Antibiotics are secondary metabolites or biochemical secreted by microorganisms. Inhibits the growth or kill other microbes. Soluble compounds derived from certain microorganisms. They are in the form of natural, synthetic and semisynthetic .

3. ANTIBIOTIC RESISTANCE It is the reduction in effectiveness of a drug in curing a disease. Loss of susceptibility of bacteria to the killing or growth inhibiting properties of an antibiotic agent. Resistance strain of bacteria : dominant…. It might be untreatable and life threatening.

4. MECHANISM OF DRUG RESISTANCE Intrinsic (natural resistance) inherent structural or functional characteristics, allows tolerance Acquired resistance changes in the usual genetic makeup

5. Several common mechanisms for drug resistance and it includes Inactivation of the antibiotic Efflux pumping of the antibiotic Modification of the antibiotic target Alternation of the pathway

6. MODIFICATION: Natural variants or acquired changes in the target sites of antimicrobials that prevent drug binding is a common mechanism of resistance. Bacteria can modify the antibiotics target to escape its activity. It acts as a self resistance mechanism against several classes of antibiotics.

7. Bacteria can change the structure of the target, but the modified target may also be able to function. This will be achieved in two ways: 1. Mutation of the gene that codes for the target protein. 2. Importing a gene that codes for a modified target.

8. Some methods of modifications: Alternation in the 30S subunit or 50S subunit Alternation in PBP Altered cell wall precursors

9. Alternation in Ribosomes Ribosomes leads to resistance to drugs that affect the protein synthesis Example : Aminoglycosides , Macrolides , tetracyline , chloramphenicol .

10. PBP: A specialized mechanism for the resistance of Gram positive bacteria The presence of mutation in the PBP, leads to the reduced affinity to beta lactam antibiotics. Examples: MRSA, Streptococcus pneumoniae .

11. CELL WALL PRECURSORS Inhibited by glycopeptides. Vancomycin or Teicoplanin , binding to the D- alanine - D- alanine residues of peptidoglycan residues. It is changed to D- alanyl -lactate, as glycopeptide do not cross link donot occur and resistance to them develops.

12. ALTERNATION OF THE TARGET SITE Alternation has been supposed to many antibiotics including : Beta lactams , Quinolones , Glycopeptides, Chloramphenicol . Some drugs competitively inhibit metabolic pathways. Bacteria can overcome this method by using an alternative pathway.

13. Beta Lactam antibiotics Major mechanism involves the enzymatic action of Beta lactam . Some other mechanisms also included: PBP MRSA Alternations to PBPs.

14. Streptomycin It works on the mechanism of alternations in the ribosomal subunit. Due to mutation changes in the protein structure occurs, which prevents the binding of streptomycin . It induces the bacteria with resistance to very high concentration of the drug.

15. Chloramphenicol & Erythromycin Alternations in the ribosomal subunit have been implicated in resistance to both the antibiotics. Erythromycin resistance results more from methylation of the 23S ribosomal RNA subunit. Dissociated resistance.

16. Fusidic acid Inhibiting the translocation of the growing polypeptide chain. Mutational alternation

17. Quinolones Enzymatic target of antibiotic DNA gyrase and DNA topoisomerase II.

18. Rifampicin Alternation to the beta subunit of RNA polymerase.

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