Principle 4- Part B Flashcards
_______ can impact pathogen by targeting some
function necessary for its reproduction or
survival
antimicrobial agents
When antimicrobial agents are targeted function is very specific to pathogen ______ _____ _____ occurs
high therapeutic index
the following antimicrobial agents, b-lactams, Glycopeptides, and Polypeptides, are involved in disruption of the ____ ____ ____.
bacterial cell wall
– peptidoglycan repeat unit forms in cytoplasm • involves use of uridine diphosphate (UDP) as a carrier – repeat unit then transported across membrane by bactoprenol (“lipid”) – repeat unit attached to growing peptidoglycan chain – cross-links formed by transpeptidation
Steps of peptidogylcan synthesis.
________ creates crosslinks in peptidoglycan
Transpeptidation
_________ is the exchange of one peptide bond for another
Transpeptidation
_______ antibiotics inhibit transpeptidation
b-lactam
_______ is a ring structure that is similar to the D-ala —– D-Ala bond
b-lactam
high activity against most gram positive bacteria. low against gram negative; destoryed by acid and penicillinase.
Penicillin G
More acid resistant than penicillin G
Penicillin V
Active against gram + and gram - bacteria; acid stable
ampicillin
Penicillinase-resistant, bet less active than penicillin G; acid-labile
Methicillin
Two newer classes of b-lactam antibiotics
Carbapenems and monobactams
Not antibiotics, but help b-lactam antibiotics by preventing their degradation by b-lactamases
b-lactamase inhibitors
________ are enzymes produced by some bacteria that are resistant to b-lactam antibiotics
b-lactamases
clavulanic acid, sulbactam, and tazobactam
Examples of b-lactamase inhibitors:
________ binds terminal D-Ala-D-Ala and sterically inhibits addition of peptidoglycan subunits to the cell wall.
Vancomycin
stops production
_______ binding to existing peptidoglycan chains inhibits the transpeptidation reaction that crosslinks the chains
Vancomycin
________ has been important for treatment of
antibiotic resistant staphylococcal and
enterococcal infections
vancomycin
Vancomycin and teichoplanin are _______.
glycopeptides
______ prevent recycling of lipid carrier.
bacitracins
______ Binds phospholipids and disrupts outer and inner membranes of gram negative bacteria (topical because of more general mode of action = toxic)
polymixins
bacitracins and polymixins are exampls of ________.
polypeptides
Second line treatment for Mycobacterium tuberculosis
Cycloserine
_______ is a cyclic analog of alanine
Cycloserine
Also crosses blood brain barrier and is an NMDA receptor agonist (with uses and side effects)
Cycloserine
Inhibits Mycobacteria by affecting synthesis of mycolic acid (abundant wax in the cell wall)
Isoniazid and Ethionamide
Inhibits Mycobacteria by affecting attachment of mycolic acid in the cell wall
ethambutol
Binds 23S rRNA and prevents formation of 70s initiation complex.
Oxazolidinones (linezolid)
Bind 16s rna of 30s subunit and prevent the binding of the A site
tetracyclines
Bind to 30S subunit and distort A site, causing translation misreading, which inhibits protein synthesis.
Aminoglycosides
streptomyosin, gentamycin, tobramycin
Bind to 50S subunit and inhibit PA peptidyltransferase activity.
Chloramphenicol
Lincosamides
amino acid on the tRNA at the A site attacts the bond between tRNA amino acid at the P site
peptidyltransferase
reaction
- Bind 23S rRNA in the 50S subunit and block the translocation reaction aa#2
- also prevent formation of the 50S PA subunit
Macrolides
erythromycin, azithromycin, clarithromycin
- Disruption of bacterial cell wall
- Inhibition of
protein synthesis - Inhibition of nucleic acid synthesis
- Antimetabolites
Basic Mechanisms of Antibiotic action
Interfere with type II topoisomerases (DNA gyrase or topoisomerase IV) and stabilize DNA double strand breaks. This is important in the Inhibition of nucleic acid synthesis.
Quinolones
ciprofloxacin and other -floxacins
Inhibit the enzymes that untangle nucleic acids during DNA replication and RNA transcription
Quinolones
Bind to bacterial RNA polymerase and prevent the initiation of transcription
Rifampin & Rifabutin
- a prodrug with no inherent antimicrobial activity
* produces DNA-damaging radicals under anaerobic conditions via enzymes functioning in anaerobes and microaerophiles
Metronidazole
Stops the precursors to folic acid
antimetabolites
Sulfonamides, trimethoprim, dapsone, and p-aminosalicylic acid
Big problem for clinical treatment of infections.
_______ can often be transmitted to other bacteria
Resistance (drug resistance)
What four ways to bacteria resist antibiotics?
- impermeable membrane
- Target modification
- Antibiotic modification
- efflux pump
the bacterial cell membrane develops an impermeable barrier which blocks antibiotics
impermeable barrier
modification of components of the bacteria which are targeted by the antibiotic, meaning the antibiotic can no longer bind properly to its target in order to destroy the bacteria
target mdoification
the cell produces substances (enzyme) that degrades and inactivates the antibiotic before it can harm the bacteria.
antibiotic modification
the anitbiotic is actively pumped out of the bacteria for that it cannot harm the bacteria
efflux pump
- contains a plasmidborne
- hydrolysis of b-lactam ring by b-lactamase
penicillins, cephalosporins
- does not contains a plasmidborne
- change in penicillin-binding protein
methicillin
- contains a plasmidborne
- efflux pump pushes drug out of cell
tetracylcines
- does not contains a plasmidborne
- mutations in 23S rRNA
oxazolidinones
- does not contains a plasmidborne
- mutations in genes encoding DNA gyrase and topoisomerase IV
quinolones
- contains a plasmidborne
- change in binding site in the peptidoglycan target (D-alanine – D-alanine changed to D-alanine – D-lactate)
vancomycin
- New mutations of bacterial genes that
encode the targets of antibiotics - Pre-existing resistance genes that are
transmitted from one bacterium to another
the origin and transmission of drug resistance
some can promote their own
transfer by conjugation
plasmids
drug resistance genes are carried on ______
Plasmids
- can package non-phage DNA
= transfer by transduction
Transducing bacteriophage
- mutations
- transfer by transformation
Bacterial chromosomal genes
hop into other genetic elements
transposons
- segments of DNA containing
complete sets of genes - found on plasmids, transposons, and bacterial chromosomes
integrons
development and spread of drug-resistant pathogens caused by antibiotic treatment, which destroys drug-sensitive strains
superinfection
Killing of normal flora removes the inhibitory effect of the normal flora (which produce antibacterial substances & compete for essential nutrients). This allows for uninhibited growth of potentially pathogenic bacteria & fungi
superinfection
Clostridium difficile (spore-forming agent of pseudomembranous colitis)
MDR (multi-drug-resistant) gram-negative rods
MRSA (methicillin-resistant Staphylococcus aureus) Candida or other fungi
Common organisms in Superinfections
• give drug in high concentrations • give two or more drugs at same time • use drugs only when necessary • possible future solutions - continued development of new drug - use of bacteriophages to treat bacterial disease
Pr eventing emergence of drug resistance