Infection - Bacterial Resistance Flashcards
Intrinsic Resistance
This describes bacterial resistance to an antibiotic without acquisition of external factors, so inherent to them
What are the types of intrinsic resistance?
Efflux Pumps
Altered Target Sites
Impermeable Cell Walls
Alternate Metabolic pathways
How do Efflux Pumps work?
Substrates bind with conformational changes allowing its transport across the cell membrane, coupled with ATP hydrolysis.
What is an example of altering target cites?
PBP mutations reduce beta-lactam affinity
What is an example of protein synthesis drug resistance?
S.aureus mutations in 23s rRNA reduce affinity for arythromycin
What is the mechanism of Beta-Lactams?
Covalent linkage with the serine residue of the active site of PBP otherwise required as a nucleophile for cross-linkage.
What is an example of alternate metabolic pathways?
Folic Acid biosynthesis important for NT productions
What antibiotics inhibit Folic Acid biosynthesis enzymes?
Sulfonamide and Trimethoprim inhibit dihydropteroate synthase and dihydrofolate redcutase respectively.
How is Folic Acid inhbitance bypassed?
Absorption of envionrmnetal folate converting pre-formed folate into active tetrahydrofolate.
What is intrinsic resistance independent of?
Previous antibiotic exposure and horizontal gene transfer.
Minimum Inhibitory Concentration
This is the minimum concentration of antibiotics required that can completely inhibit growth of a microorganism
How is MIC tested?
Broth Diffusion Method
Kirky-Bauer Disk Diffusion Test
How is the Broth Diffusion Method performed?
Taking a series of tubes with increasing concentrations of the antibiotics then inoculating with test organism: incubated then MIC determined by lowest concentration awt which agent inhibits growth completelte
How is the Kirby-Bauer Disk Diffusion Test performed?
This takes a paper disk with the antimicrobial agent placed on surface of an agar plate incoulated with organism, plate incubated with zone of inhibition emasured.
Why is MIC important?
Tracking of bacterial population susceptibility and tracking AM resistance?
Acquired Resistance
This is the resistance of agents by genetic hcanges or genetic element acquisiton.
What are the three primary mechanisms of acuired resistance?
Horizontal gene transfe, mutaiton and selective pressure
Horizontal Gene Trasnfer
This is reproduction of genetic material independent of organism reproduction
What are the three types of horizontal gene transfer?
Transformaiton
Transduction
Conjugation
Transformaiton
THis is the uptake of DNA by recognition of surface receptors, faciltiated by competence factors
Transduction
This is the transfer of genetic material through bacterioophages that integrate into the genome
Conjugation
This is the trasnfer of plasmids between bacterial cells, often by plasmids carrying antibiotic resistance.
What is an example of mycobacteria drug uptake limitation?
Alteration of high hydrophobic nature using long-chain mycolic acids.
How do mycobacterial porins assist in resistance?
Ther are narrower in diameter than GNB with capacity to selectively exude hydrophilic molecules.
What is an example of a mycobaterial resistance?
Tuberculosis response to isoniazid decreases cyclopropane containing mycolic acids decreasing permeability
How is isoniazid activated?
Catalase-peroxidase which produces a reactive species altering the bacterial cell wall
How might bacteria modify drug targets?
Genetic mutations of the targets of the drug or enzymes that degrade them
What is an example of drug target alteration?
Aminoglycoside-modifying enzymes chemically modify aminoglycoside antibiotics
Aminoglycoside Antibiotics
This is a group of drugs used to treat infections by aerobic GNB
What are mechanisms of drug target alteration?
Plasmids/Transposons encoding acetyltransferases enzymes to NH3 or OH of antibiotic reducing affinit.
Over-expression of target molecule to saturate bacteria.
What is the base strucutrre of B-Lactams?
Beta Lactam Ring
What are examples of the differences of beta lactam ring structure?
Cephalosporins have a dihydrothiazine ring fused to the b-lactam ring
Carbapenems have a five-membered ring fused to a b-lactam ring
What is the structre of the b-lactam ring?
Four memebred ring containing an amide group and a carbonyl group, both being polar
What is the mechanism of action of B-Lactams?
Inhibitio nof PBP in pg cell wall synthesis
How does the carbonyl and serine interact?
Serine partial positive whilst carbonyl partially negative, forming a covalent bond stabilised by h-bonding of amide group to AA residues in active site.
What do B-Lactams mimic?
D-Alanine poriton of the PG precursor.
What is an example of resistance to B-Lactams?
Methicillin-Resistant Staphylococcus Auresus through PBP2a gene with lower affinity to beta-lactams through mecA gene acquitisiiton.
What is the most common form of acquired resistance?
Plasmid acquistion taken up by outside material
What is the mutation rate of bacteria?
about 1 of every 10^6 to 10^9 per nucleotide per cell divisions.
How might biofilm protect against drug activity?
Due to being sessile thus minimal metabolic activity/PBP to activate.
Vancomycin
An AB inhibiting cell wall formation as an alternative for people allergic to penicillin.
