Block I

Question 1

Abscess

Answer 1

localized collection of pus caused by seeding of microorganisms in tissue surrounded by a fibrin0rich pseudocapsule. this leads to diminished access to host defenses and antimicrobial agens

Question 2

4 bacterial shapes

Answer 2

cocci- spherical
bacilli- rods
rigid spirals are spirilla
spirochetes (think tightly coiled bacteria)

Question 3

Gram positive bacteria: wall characteristics and color

Answer 3

thick peptidoglycan layer retains crystal violet color: blue

Question 4

gram negative bacteria: wall characteristics and color

Answer 4

outer membrane/envelope: LPS (lipopolysaccharide). includes lipid A, which is called an endotoxin bc it causes inflammation; o-specific polysaccharides are antigenic and confer serotype specificity
stain red with safranin

Question 5

spores

Answer 5

produced by some gram pos bacilli. withstand heat, desiccation, radiation, and antibacterial agents

Question 6

capsule

Answer 6

polymeric network external to the cell wall made of polysaccharides and peptides/proteins. supports colonization, provides resistance to drying, provides resistance to phagocytosis;

Question 7

In what four ways can bacteria develop resistance to antibiotics?

Answer 7

mutated drug receptor causes the drug to have less affinity for its target.
acquisition of one or more enzymes that pprovide an alternate metabolic pathway to bypass the effect of the drug/target interactions
drug inactivation
decreased influxe or increased efflux of the drug

Question 8

major mechanisms of action of antibiotics

Answer 8

inhibit cell wall synthesis; inhibit protein synthesis; inhibit dna synthesis; inhibit RNA synthesis; inhibit folate biosynthesis; disrupt membrane potential, woot woot

Question 9

What kind of bacteria (gram stain) has the highest osmolarity?

Answer 9

gram positive

Question 10

what enzymes are involved in bacterial wall synthesis?

Answer 10

transglycosylases and transpeptidases. gransglycosylases catalyze the addition of the repeating aminosugar subunits NAM and NAG to the peptidoglycan backbone
transpeptidases catalyze the crosslinking of the peptidoglycan to give it strength

Question 11

beta lactams: examples, MOA (general)

Answer 11

examples: penicillins, cephalosporins, monobactams, carbapenems. they inhibit transpeptidases that catalyze the cross-linking of peptidoglycan

Question 12

vancomycin

Answer 12

glycopeptide antibiotic that binds to a specific site on the peptidoglycan in the cell wall of susceptible bacteria and blocks elongation and cross-linking of the peptidoglycan by inhibiting both transglycosylase and transpeptidase rxns.

Question 13

penicillins: MOA, MOR,

Answer 13

MOA: bind proteins in the bacterial cytoplasmic membrane called penicillin binding proteins. beta lactams bind the active site of transpeptidases and block the cross-linking rxn. PBPs are also autolysins that are normally involved in cell division; beta lactams inappropriately activate these enzymes and cause breakdown of the cell wall.
MOR: PBP called beta lactamase.can break them down. found in the periplasmic space of gram negative bacteria and on the surface of some gram pos bacteria
alternately, PBP mutations can reduce beta-lactam affinity.

Question 14

penicillin V and G

Answer 14

narrow spectrum beta lactamase sensitive drugs
effective against gram pos organisms and gram neg cocci
most staph and gonococci now resistant
penG is acid sensitive (not a good oral drug)

Question 15

ampicillin, amoxicillin

Answer 15

extended spectrum beta lactamase sensitive drug
activity against gram neg organisms and improved acid stability when compared with Pen G. exp. Hib, salmonella, and shigella

Question 16

cabeninicllin, ticarcillin

Answer 16

extended spectrum beta lactamase sensitive drugs also effective aganst pseudomonas

Question 17

clavulanic acid

Answer 17

often taken with extended spectrum beta lactamase sensitive drubs because it inhibits beta lactamase

Question 18

methicillin, nafcillin, oxacillin. uses and acid stability and side effects

Answer 18

typically used for beta lactamase producing staph

methicillin: acid sensitive and can be nephrotoxic
nafcillin: better anti staph activity than methicillin
oxacillin: acid stable

Question 19

1st generation cephalosporin

Answer 19

active against gram pos cocci and better than penicclin against gram neg rods

Question 20

2nd generation cephalosporin

Answer 20

active against gram pos cocci and gram neg rods, like 1st gen, but also better at killing beta-lactamase producing gram negatives

Question 21

3rd generation cephalosporin

Answer 21

better than the others at beta lactamase stability so more activity against gram neg infections.

Question 22

4th generation cephalosporin

Answer 22

broadest gram pos and gram neg spectrum; active against pseudomonas

Question 23

vancomycin: uses, MOA, MOR, side effects

Answer 23

chemically and mechanistically distinct from beta-lactams
blocks transpeptidases by binding to the pentapeptide chain in peptidoglycan precurosrs
only active against gram positive organisms
used for serieos Staph and enetrococcus infections
riesntance due to altered pentapeptide
side effects are nephrotoxicity and ototoxicity

Question 24

aminoglycosides: structure, MOA, MOR, use, side effects; stability

Answer 24

structure: polycationic compounds of aminosugars linked through glycosidic bonds
MOA: hydrophilic compounds enter gram neg bacteria thru porins in outer membrane and bind to 30S ribosomal to prevent formation of the ribosomal initiation complex. mRNA is misread.
MOR: upregulation/acquisition of aminoglycoside-modifying enzymes that change the drug
Uses: synergistically w/ beta lactams; for grem neg rod infections and as a 2nd line of defense against TB
Pharm: ionized at physiologic pH- limited oral absorption
side effects: ototoxicity, nephrotoxicity (reversible)

Question 25

macrolides. example, structure, MOA, MOR, use, toxicity

Answer 25

ex.: erythromycin (also clarithromycin, azithromycin)
structure: large lactone ring with one or more deoxy sugars.
MOA: binds 23 S rRNA, which is part of the 50S ribosomal subunit and blocks translocation of peptidyl tRNA. bacteriostatic.
MOR: modification of the drugbinding site on the rRNA by methylases
USes: alternative to penicillin for strep infections, also for legionella, chlamydia, mycoplasma
toxicity: rare. ototoxicity, drug interactions due to inhib of P450

Question 26

tetracyclines. MOA, MOR, side effects, use, examples

Answer 26

MOA: bacteriostatic by binding to 30S subunit and preventing tRNA attachment
MOR: pumps that can get the drug outside of the cell
side effects: GI disturbances, discoloration of teeth, bone growth changes in kids, photosensitivity, superinfection with candida
use: broad spectrum but limited by resistance
examples: doxycycline, minocycline, chlortetracycline

Question 27

tigecycline

Answer 27

similar to tetracyclines but part of a class of glycycyclines. more effecitve against bacteria that have acquired resistance through drug efflux pumps

Question 28

chloramphenicol and clindamycin. MOA and sides

Answer 28

MOA: bind to the 50S ribosomal subunit and inhibit peptidyl transferase (no peptide bond formation)
chloraphenicol side effects: bone marrow suppresion but can be used as a back up
clindamycin: also causes diarrhea, rahses, superinfection

Question 29

linezolid

Answer 29

oxazolidinone antibiotics that bind the 50S ribosomal subunit to block formation of the initiation complex. bacteriostatic against MRSA, VRE, strep pneumoniae, and other gram pos organisms.

Question 30

fluoroquinolones. examples, MOA, MOR, use, sides

Answer 30

MOA: block DNA replication by inhibiting DNA gyrase and topoisomerase
ex. norfloxacin, ciprofloxacin, levofloxacin
MOR: increased activity of intrinsic efflux pumps and mutations in target enzymes
uses: UG and GI infections by gram neg bacteria
sides: GI disturbances

Question 31

what are the inhibitors of folate biosynthesis? what are the MORs? spectrum? toxicity?

Answer 31

sulfonamides and trimethoprim
widespread resistance due to decreased drug accumulation, increased PABA production, and mutations in dihydroopteroate synthestase and dihydrofolate reductase. broad sprectrum. can be hemotoxic, nephrotoxi, kernicterus in neotnates.

Question 32

sulfonamides: structure, MOA,

Answer 32

struture: analogs of folic acid precursor p-aminobenzoic acid
MOA: bacteriostatic. competitive inhibition of dihydropteroate synthetase (needed to make folic acid from PABA. human cells, in contrast, use preformed folic acid.

Question 33

trimethoprim

Answer 33

blocks folic acid synthesis by competitive inhibition of dihydrofolate reductase. human cells use dihydrofolate reductase but are less sensitive than bacteria to trimethoprim blcoks folic acid syntheisis by competitive inhibition of dihydrofolate reductase.

Question 34

TMP-SMX aka co-trimoxazole aka trimethoprim + sulfamethoxazole

Answer 34

treats compex UTIs, and shigella, salmonella, and penumocystis carinii pneumonia

Question 35

daptomycin

Answer 35

lipopeptide antibiotic.
MOA: Ca dependent binding and insertion into gram pos bacteria. basically a lytic peptide. good against gram pos bacteria

Question 36

conjugative plasmid vs. non-conjugative plasmid

Answer 36

conjugative plasmids encode conjugal transfer system and are large and have a single copy/chromosome.
non-conjugative chromosomes can’t promote conjugal DNA transfer and are small and multicopy.

Question 37

f factor

Answer 37

fertlility/sex factor.

plasmids that carry genes that encode the ability of bacteria to undergo conjugal transfer of genetic info

Question 38

insertional elements vs. transposons (bacteria)

Answer 38

transposons: jumping genes that contain one or more antibiotic resistance gene. insertional elements can insert themeselves into different sites of the bacterial chromosome but don’t carry resistance genes. can jump btw positions on chromosome or btw a chromosome and a plasmid

Question 39

structure of transposable elements

Answer 39

1. transposase: enzyme required for transposition of a prticular element
2. contain short inverted repeat sequences at the ends that are recognized by the transposase
3. after insertion, transposable elements are flanked by a short direct repeat of host DNA

Question 40

IS sequence

Answer 40

insertion sequence that is a transposable nucleotide sequence that encodes only fnctions related to its own transposition

Question 41

TN

Answer 41

transposons: a transposable genetic element that encodes proteins needed for its own transposition as well as one or more new recognizable phenotypes on the host cell

Question 42

merozygote

Answer 42

temporary parital diploid that is formed upon entry of DNA into a recipient cell

Question 43

bacterial transformation

Answer 43

naked DNA is liberated from the donor bacteria upon cell lysis and is take up by the recipient bacteria. homologous recomb occurs- donor dna replaces the original dna of the recipient. demonstrated by the griffith experiments (dead mice with the rough vs. smooth viruses)

Question 44

bacterial transduction

Answer 44

bacteriophage is used to transfer DNA from donor to recipient.esp. common among gram neg enterobacteria, also S. aureus and C. diphtheriae

Question 45

bacterial conjugation

Answer 45

cell to cell contact required. occurs btw bacteria thru a highly differentiated structure known as a sex pilli.

Question 46

when are bacterial cells competent for transformation?

Answer 46

usually late in the log phase of growth and when they are producing competence factors that bind or trap transforming DNA at specific sites on the cell surface. and endonuclease can then degrade one strand and propel the other strand into the cell. this ssDNA then pairs with a homologous region of the recipient chromosome and integrates

Question 47

generalized transduction vs. specialized transduction

Answer 47

generalized: bacteriophase infection initiates the lytic cycle. the bacterial chromosome is broken into pieces, and occassionally a piece is packaged into a phage particle. the phage infects a new host, which gets dna from the previously infected host.
or, specialized transduction: viral integration occurs (lysogenic cycle). it involves the transduction of specific chromosomal genes adjacent to the viral integration site. phage DNA inserts itself into the bacterial host chromosome at a particular site. when it replicates, it might take a piece of the adjacent bacterial genes with it. only genes adjacent to the insertion site can be transferred in that way.

Question 48

Conjugation: steps

Answer 48

1. F pilus from the donor binds to the surface of the recipient cell and bring the two cells in contact with each other.
2. transfer begins at oriT. ssDNA is transferred from the donor to the recipient.
3. F DNA is replicated as the transfer is occurring.
   After mating, both cells contain an F factor.

Question 49

What are the two components of most conjugal R plasmids?

Answer 49

the resistance transfer region (RTF controls replication ,copy number and transfer functions) and the resistance determinant segment.

Question 50

what are the three levels of genetic organization at wich resistance can evolve?

Answer 50

1. clonal: dissemination of a given strian which contains an R plasmid
2. R plasmid dissemination where a plasmid moves from strain to strain or species to species
3. plasmid to plasmid via transposition

Question 51

integrons (functional definition)

Answer 51

recombinational hot spots for site specific recombination events between largely nonhomologous sequences of DNA. inother words, areas/sites that recombine even though the DNA isn’t particularly homologous. they were discovered by looking at R plasmids/transposons that seem to carry the same resistance genes but aren’t otherwise homologous.

Question 52

integrons: what sites do they condaint? how do they work?

Answer 52

contain the attI site. attI sites are sites at which gene cassette DNA can be integrated by site-specific recombination. this site also encodes the integrase enzyme that mediates site-specific recombination events. Many integrons also have a sul gene: sulfonamide resistance gene.

Question 53

what are gene cassettes?

Answer 53

small amts of DNA that generally contain only a single gene and a short sequence that allows for specific recombintation with integron sites (this short sequence is about 59 bps long).. genes on cassettes lack promoters: they use promoters on the integron next to the attI site.

Question 54

what is a pathogenicity island?

Answer 54

certain genes are commonly found in instrains of bacteria isolated from clinical disese but are absent from isolates of the same species. pathogenicity islands are specific regions of crhomosomal DNA (aka Pais). Pais are fragments of DNA that include a number of virulence genes and are the result of chromosomal integration of a mobile genetic element. Basically, Pais are regions of the bacterial chromosome that attract mobile elements that carry genes important for pathogenicity. they have different GC content in comparison to host bacterial dna. they tend to be associated with tRNA genes or IS elements and have mobility genes as well.