5. Why are aminoglycosides more selectively toxic to bacteria than human cells?

Question

5. Why are aminoglycosides more selectively toxic to bacteria than human cells? (Be sure to be complete and specific in your answer to make it clear why these drugs are more toxic to bacterial cells than to human cells.)

6. Penicillins and cephalosporins are beta-lactam antibiotics. Plasmids coding for beta-lactamase enzymes make the bacterium resistant to these antibiotics. What do beta-lactamases do?

7. Methicillin resistant strains of Staphylococcus aureus (MRSA) are resistant to penicillins and often to cephalosporins. Vancomycin is sometimes the only antibiotic that can be used to effectively treat MRSA infections. Refer to the diagram of peptidoglycan below to answer the question. The [L-alanine/D-glutamic acid/L-lysine/4th D-alanine/5th D-alanine] in the left chain binds to the [L-alanine/D-glutamic acid/L-lysine/4th D-alanine/5th D-alanine] in the right chain after release of the [L-alanine/D-glutamic acid/L-lysine/4th D-alanine/5th D-alanine] from the right chain.

Explanation / Answer

5)Aminoglycosides are more toxic than most other antibiotic classes, they have important therapeutic applications for the treatment of a number of aerobic gram-negative bacteria, mycobacteria, and some protozoans. They interact with the 30s ribosome subunit of the prokaryotic cells and disrupts the proteins synthesis which is necessary for the protein synthesis. Aminoglycoside antibiotics, such as streptomycin, gentamicin, tobramycin, and kanamycin, are potent antibiotics used in the treatment of serious infections caused by Gram-negative bacteria. Eukaryotes like humans lack 30s subunit of ribosome which is posses by the prokaryotes by which it is more effective against prokaryotes compared to eukaryotes.

6) Beta lactam antibiotics include penicillin and cephalosporin which attack the cell membrane and ruptures the cell leaking the cell contents. The cell wall is made of peptiodglycan made up of N acetyl muramic acid(NAM) and N acetyl glucosamine(NAG) which are join by the chain of four amino acids. The NAM and NAG are cross linked by the enzymes transpeptidase enzyme which has also high affinity for beta lactam drugs. The transpeptidase combine with beta lactam drugs and prevent the cross linking of NAM and NAG thus the cell wall formation is prevented but is the bacteria can synthesis the Penicillinase enzyme which acts the beta lactam ring and makes it open making it ineffective thus how Penicillinase acts on the beta lactam ring.

7) Methicillin resistant bacteria are able to synthesis Penicillinase enzyme which can escape the effect of beta lactam and cephalosporin drugs. The NAM and NAG subunits of the bacterial cell wall are cross linked by D alanine subunits tow NAM and NAG units have D alanine at their terminus which are joined together to form the cell wall which is accomplished by the enzyme trans glycosidase. On treatment with vancomycin the glycosidase is replaced with the vancomycin by which there is no linkage of D alanine subunits and cell wall breaks leading to cell death.

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