Lecture 14: Mechanisms of Resistance to Antibiotics Flashcards
What is intrinsic or natural resistance to antibiotics?
innate ability through inherent structural or functional characteristics
Which two bacteria have innate antibiotic resistance?
M. tuberculosis
Pseudomonas aeruginosa
What is mutational resistance to antibiotics? How do these mutation arise?
chromosomal muation
- random/spontaneous
- exposure to antibiotic
How does acquired antibiotic resistance happen?
horizontal gene transfer - neighboring bacteria swap genetic material
Where are many genes for antibiotic resistance located?
Plasmids, transposons, or integrons
What are the three methods of horizontal gene transfer?
Transformation
Conjugation
Transduction
What are the seven identified mechanisms of antibiotic resistance
enzymatic inactivation decreased permeability efflux alteration of target site protection of target site overproduction of target bypass of inhibited process
Beta lactamases (penicillinases) employ which mechanism of antibiotic resistance?
enzyme inactivation - split amide bond of Beta-lactam ring
Where are bla (Beta-lactamase genes) encoded?
transferable genes (plasmids, transposons), integrons
What are Extrended-Spectrum Beta-lactamases (ESBLs)?
resistance to 3rd gen cephalosporins, but do not affect carbapenems
What are common ESBLs?
Kelbsiella, E coli, Proteus, other Enterobacteriaceae
Which antibiotic is used to treat ESBLs?
carbapenem
What are Amp C beta-lactamases?
chromosomal enzymes for resistance
not susceptible to beta-lactamase inhibitors
Where are Amp C beta-lactamases found?
Enterobacteriaceae, Kelbsiella, E coli
which category of beta-lactamases offer the largest antibiotic resistance spectrum?
carbapenemases
Which four classes of antibiotics are used against a beta-lactamase producing organism?
Penicillinase-Resistant Penicillins
Beta-Lactamase Inhibitors and Inhibitor Combinations
Extended Spectrum Cephalosporins (3rd and 4th gen)
Carbapenems
How does decreased permeability of bacterial membranes work as a mechanism of antibiotic resistance?
alter porins so antibiotics aren’t compatible
larger, more negative, more hydrophobic antibiotic molecules are less likely to get through
How does antibiotic efflux work as a mechanism of antibiotic resistance?
moved out of cell
What two common classes of antibiotics are effluxed from bacteria as a mechanism of resistance?
tetracycline
beta-lactams
What kinds of target sites do bacteria alter as a mechanism of resistance?
Ribosomal target sites
Cell wall precursor target sites
Target enzymes
Protection of target sites
from which class of bacteria did vancomycin-resistant S. aureus acquire the gene complex for altering cell wall precursor target sites?
Enterococci
What target sites can bacteria alter to be resistant to beta-lactams?
alter Penicillin Binding Proteins
What gene confers MRSA its resistance? what type of resistance is this?
mecA gene - on a cassette
alteration of target enzymes
Give an example of how altered metabolic pathway mechanism of resistance works
Enterococci needed folic acid
Antibiotics were made to inhibit folic acid (ex. sulfa drugs)
Enterococci became folate auxotrophs - no longer required folic acid, resistant to effects of antibiotic
