antibiotics and antibiotic resistance Flashcards
what are disinfectants?
antimicrobial agents applied to inanimate objects – toxic!
what are antiseptics?
antimicrobial agents that are sufficiently nontoxic and can be applied to living tissue
e.g. hand sanitizer
what are antibiotics?
antimicrobial agents produced by bacteria and fungi that are exploited by humans
delivered topically (specific area) and internally
they specifically target microbes and can be applied intramuscularly or intravenously
what’s the most effective therapeutic agent against bacterial infections?
antibiotics
availability enabled chemotherapy, organ transplantation, invasive surgeries & treatment of
premature infants
what are the 2 major problems with developing antibiotics?
bacterial resistance
diminished interest from big pharmaceutical companies to develop new antibiotics (trouble making money)
describe misuse of antibiotics
empiric (blinded) use (treating with any antibiotic on hand)
— may only be used if symptoms are severe & diagnosis is too slow
increased use of broad-spectrum agents (kills off other bacteria)
pediatric use for viral infections
do not complete course of treatment (those that survive may be resistant – bacteria remerges, stronger)
antibiotics in animal feeds (growth promotors)
how is antibiotic activity measured?
via minimum inhibitory concentration (MIC)
^^ the lowest concentration of agent that inhibits bacterial growth
how does one obtain the minimum inhibitory concentration?
series of culture tubes w/ varying concentrations of agent
– check for visible growth
can also use antibiotics strips; faster & multiple
– each strip has a different antibiotic w/ increasing concentration from bottom to
top
– MIC tells tell you antibiotic sensitivity in bacteria & how much you need to kill it
how do antibiotics work?
they target essential bacterial components
– such as cell wall synthesis
– protein synthesis
– DNA/RNA synthesis
– folate or folic acid synthesis
—– folic acid is required for nucleotide synthesis (so it’s starving the microbe)
– cell membrane alteration
describe beta-lactam antibiotics
contains a beta-lactam ring
inhibits cell wall synthesis
what type of antibiotic inhibits cell wall synthesis
beta-lactam antibiotics
how do some bacteria counteract penicillin, the antibiotic?
produces beta-lactamase, enzyme that destroys the beta-lactam ring – and as a result, the antibiotic
what’s methicillin?
chemically modified penicillin
also contains a beta-lactam ring
can’t be cleaved by beta-lactamases
… but some bacteria can produce a different “penicillin-binding proteins” e.g. PBP2a - encoded by ‘mec’ (methicillin resistance) — helps bacteria fight against antibiotics including methicillin
how does penicillin function as an antibiotic?
inhibits cell wall synthesis
it inhibits the penicillin-binding proteins (PBPs) aka transpeptidase in bacteria that help form the cross-links in cell wall – this makes the cell wall toooo weak, causing cell death
what is vancomycin?
a glycopeptide antibiotic that inhibits cell wall synthesis in gram+
— vancomycin can’t get across the cell membrane of gram- so doesn’t work there!
often a drug of “last resort”
how does vancomycin inhibit cell wall synthesis in gram+ bacteria?
binds the peptide linkage at terminal D-Ala-D-Ala residues & inhibits transpeptidation
resistance genes change these to D-Ala-D-Lac
– vancomycin can no longer bind
resistance is encoded by the van genes
what’s antibiotic resistance?
use of antibiotics actively selects for antibiotic resistant bacteria
in many cases, bacteria acquire a new gene (not just a series of single mutations)
antibiotic resistance can increase 1000-fold in a strain
what are some bacterial strategies for antibiotic resistance?
prevention of antibiotic entry
— gram- outer membrane & mycobacteria cell envelope block antibiotics from entering cell
antibiotic modification
— beta-lactamase destroy antibiotic
efflux of antibiotic
— bacteria encode efflux pumps that actively pump antibiotic out of cell
alteration of antibiotic target
— PBPs, ribosome modifications (prevents protein synthesis)
bypassing the antibiotic action
— use environmental folic acid (folic acid synthesis inhibitors)
describe antibiotic resistance genes
many mechanisms of antibiotic resistance are genetically encoded (e.g. mec, beta-lactamase, efflux
pump)
— can produce very high levels of antibiotic resistance
often encoded on mobile genetic elements (e.g. plasmids)
— allows for horizontal gene transfer → “superbugs”
— can be resistant to 10-15 clinically resistant antibiotics
what is horizontal gene transfer?
new genes are acquired from another source, rather than altering gene function via. mutations
what are the 3 ways in which horizontal gene transfer can occur?
bacterial transformation
— cell dies & releases DNA; another cell takes up resistant gene
– least common, requires a lot of energy from bacteria
bacterial transduction
— bacteriophage infects bacteria, packages host antibiotic resistant
gene & injects it into a the recipient cell
bacterial conjugation
— plasmids move DNA from one cell to another via pili (VERY EFFICIENT)
what’s bacterial transformation?
cell dies & releases DNA; another cell takes up resistant gene
least common, requires a lot of energy from bacteria
what’s bacterial transduction?
bacteriophage infects bacteria, packages host antibiotic resistant gene & injects it into a the recipient cell
what’s bacterial conjugation?
plasmids move DNA from one cell to another via pili (VERY EFFICIENT)
what’s klebsiella pneumoniae? what type of bacteria is it? what does it cause? etc.
a gram- bacterial pathogen
important cause of nosocomial pneumonia (hospital-acquired pneumonia)
produces a capsule
— commonly resistant to multiple antibiotics
what’s NDM-1?
New Delhi Metallo-beta-lactamase-1 aka cabarpenemase, an enzyme
its first documented source was Klebsiella pneumoniae
NDM-1 is now widespread in other Gram negatives
= CRE (carbapenem resistant Enterobacteriaceae) is a fairly new problem
what are carbapenem antibiotics?
beta-lactamase resistant beta-lactams w/ broad-spectrum activity
– antibiotics for NDM-1 aka carbapenemase which is found in Klebsiella pneumoniae and other gram- bacteria
what was the first documented source of NDM-1?
Klebsiella pneumoniae
what’s clostridia? what type of bacteria is it? where is it found? what can it cause?
gram+
rod-shaped
endospore formers! (forms endospores)
strict anaerobes (no oxygen for them! or else they die…)
— generally found in soil and intestinal tracts of animals
can cause life threatening diseases mediated by exotoxins
where can clostridia be found?
generally found in soil and intestinal tracts of animal
strict anaerobes (no oxygen for them! or else they die…)
what does clostridioides difficile (c. diff) cause?
mild to moderate diarrhea
life-threatening pseudomembranous colitis (aka antibiotic-associated diarrhea)
or it can be asymptomatic in the large intestine (carrier state)
what does clostridium tetani cause?
tetanus
what does clostridium botulinum cause?
botulism
what does clostridium perfringens cause?
food-borne illness & gas gangrene (in soldiers)
where is clostridioides difficile (c. diff) often found?
nursing homes and hospitals
its endospores are difficult to eradicate from the environment
what’s the mode of transfer for clostridioides difficile (c. diff)?
spores thru the fecal-oral route
what is pseudomembranous colitis?
inflammatory condition of the large intestine
most important risk factor is having recently received an antimicrobial agent which may develop this bacterial infection
— symptoms may occur 1-2 days after antibiotics or several weeks after the antibiotic is continued
lesions can enlarge to cover substantial portions of inflamed mucosa and can be stripped off – this is the pseudomembrane (“false membrane”)
what are the symptoms of pseudomembranous colitis?
offensive smelling diarrhea
abdominal pain
fever
nausea
dehydration
how does pseudomembranous colitis occur?
antibiotics cure infections, but also kill normal microbiota
suppression of normal microbiota + persistence of C. difficile endospores
after antibiotic is stopped, spores germinate, leading to the overgrowth of C. difficile which occurs w/
production of toxins
C. difficile is not considered an invasive bacterium (it does not invade itself), but the
exotoxins cause damage and inflammation to the intestinal
lining of the large intestine – its exotoxins are invasive!!
describe the exotoxin produced by clostridioides difficile (c. diff)
A-B toxins aka large clostridual cytotoxins
“A-B” serves to designate two domains
A domain denotes the active portion of the toxin that carries the enzymatic activity that inactivates key regulatory proteins of the host cells, causing dysregulation of multiple cell processes including cytoskeletal rearrangements, cell death, and inflammation
B domain denotes the portion of the toxin molecule responsible for binding and uptake by the host cell
how is clostridioides difficile (c. diff) diagnosed?
history (antibiotic use), symptoms and laboratory tests to confirm C. difficile
endoscopy and toxin detection assays
what is treatment for clostridioides difficile (c. diff)?
discontinue antibiotic if still being used
provide fluids
antibiotics more specific for “C. diff” –– oral vancomycin or I.V metronidazole
— vancomycin is not a very good antibiotic; not absorbed well when taken orally, BUT… we want that here ??
avoid antidiarrheal agents as this would cause decreased toxin clearance
this is essentially using different antibiotics to treat a disease initially caused by antibiotics
what is fecal microbiota transplantation?
replaces unhealthy bacteria in the colon with healthy bacteria from a donor
helps to rebalance the microbiota, or bacteria and other organisms, in the intestines.
