L47 Bacterial genetics 4nS .pdf

A specific type of drug resistance is when a microorganism has the ability to withstand the effects of antibiotics. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying evolutionary stress to a population. ANTIBIOTIC RESISTANCE...

A specific type of drug resistance is when a microorganism has the ability to withstand the effects of antibiotics. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying evolutionary stress to a population. ANTIBIOTIC RESISTANCE Genetic basis of drug resistance MUTATIONAL DRUG RESISTANCE Chromosomal mutations typically either change the target of the drug so that the drug does not bind or change the membrane and does not penetrate well into the cell. Chromosomal mutations occur at a low frequency (perhaps 1 in 10 million organisms), and often affect only one drug or one family of drugs. Genetic basis of drug resistance TRANSFERABLE DRUG RESISTANCE Plasmids cause drug resistance by encoding enzymes that degrade or modify drugs. Plasmid-mediated resistance occurs at a higher frequency than chromosomal mutations, often affecting multiple drugs or families of drugs. Comparison between Mutational and Transferable Drug Resistance MUTATIONAL DRUG RESISTANCE TRANSFERABLE DRUG RESISTANCE One drug at a time Multiple drug resistance Low degree resistance High degree resistance Can be overcome by high drug dose High dose ineffective Prevented by combination of drugs Can not be prevented by combination of drugs Resistance does not spread Spreads to same or different species Mutant may defective Not defective Low virulence of bacteria High virulence of bacteria ACQUIRED RESISTANCE THROUGH: MUTATION HORIZONTAL GENE TRANSFER RESISTANCE OBSERVED • Mycobacterium tuberculosis resistance to rifamycins • Resistance of many clinical isolates to luoroquinolones • E.coli, Hemophilius influenzae resistance to trimethoprim MECHANISM INVOLVED Point mutations in the rifampin-binding region of rpoB Predominantly mutation of the quinolone-resistancedetermining-regiont (QRDR) of GyrA and ParC/GrlA Mutations in the chromosomal gene specifying dihydrofolate reductase Via acquisition of mecA genes which is on a mobile genetic element called “staphylococcal cassette • Staphylococcus aureus resistance to methicillin chromosome” (SCCmec) which codes for penicllin (MRSA) binding proteins (PBPs) that are not sensitive to ßlactam inhibition • Resistance of many pathogenic bacteria against Mediated by the horizontal transfer of foreign folP sulfonamides genes or parts of it Via acquisition of one of two related gene clusters • Enterococcus faecium and E. faecalis resistance VanA and Van B, which code for enzymes that to vancomycin modify peptidoglycan precursor, reducing affinity to vancomycin.