CHAPTER 20 ANTIBIOTIC RESISTANCE - Kennesaw ….pptVIP

Bacteria use several mechanisms to become antibiotic-resistant: Inactivation of the antibiotic Efflux pumping of the antibiotic Modification of the antibiotic target Alteration of the pathway Inactivation involves enzymatic breakdown of antibiotic molecules. A good example is β-lactamase: Secreted into the bacterial periplasmic space Attacks the antibiotic as it approaches its target There are more than 190 forms of β-lactamase. E.g of lactamase activity in E.coli and S. aureus (read pg 469). Efflux pumping is an active transport mechanism. It requires ATP. Efflux pumps are found in: The bacterial plasma membrane The outer layer of gram-negative organisms Pumping keeps the concentration of antibiotic below levels that would destroy the cell Genes that code for efflux pumps are located on plasmids and transposons. Transposons are sequences of DNA that can move or transpose move themselves to new positions within the genome of a single cell.Transposones: Readily acquired by nonresistant bacteria Transforms them into resistant bacteria Some bacteria reduce the permeability of their membranes as a way of keeping antibiotics out. They turn off production of porin and other membrane channel proteins. Seen in resistance to streptomycin, tetracycline, and sulfa drugs. Bacteria can modify the antibiotic’s target to escape its activity (pg470) Bacteria must change structure of the target but the modified target must still be able to function. This can be achieved in two ways: Mutation of the gene coding for the target protein Importing a gene that codes for a modified target E.g. with MRSA (methicillin- resistant - S. aureus ), similar to PBP (penicillin- binding- protein) Bacteria have PBPs in their plasma membranes. These proteins are targets for penicillin. MRSA has acquired a gene (mec A) that codes for a different PBP. It has a different three-dimensional structure. MRSA less sensitive to penicillins. MRSA is resistant to all β-lactam antibiotics, cephalosporins, and