DPT III Exam 1

how long have bacteria been on the planet for

3.5 billion years

what oxygenated the environment

cyanobacteria

Beta methyl amino alanine (BMAA)

disincorporated ay serine into proteins and is linked to protein misfolding, found in marine, crosses BBB

microcystin damages what organ?

liver

OA and DTX cause

DSP (potent tumor promoter)

domoic acid

amnesic shellfish poisoning (nausea, headache, seizure, death)

saxitoxin (STX)

paralytic shellfish poisoning, warfare

anatoxin (very fast death factor)

similar structure to cocaine, causes convulsions leading to death. Acts on nicotinic acetylcholine receptors on CNS and muscles (livestock)

vibrio vulnificus

gram negative bacteria, contaminated shellfish leading to sepsis (oysters) with a 25% mortality rate

how to tx vibrio vulnificus

ceftriaxone and doxycycline

proteobacteria

phylum of gram - bacteria

Alphaproteobacteria

oloigotroohs, taxa chlamydis and rickettsias are obligate intracellular pathogens feeding on cells of host organisms

Betaproteobacteria

eutrophs, they include human pathogens of genus nusserua and bordaretella

Gammaproteobacteria

Largest and most diverse class of proteobacteria, pseudomonas

r. rickettsia causes

Rocky Mountain spotted fever

chlamydia

gram negative, oblatory intracellular bacteria

ehrlichia

very small gram negative, obligatory intracellular bacteria can be transmitted cell to cell, ticks, causes ehrlichoisis (destruction of WBC)

alphaproteeobacteria can survive on minimal amounts of nutrients however, the BLANK are BLANK meaning they require copious amounts of nutrients

betaproteobacterua, eutrophs

bordatella

aerobics very fastidious, pertussis (whooping cough)

burkholderia

aerobic, aquatic, causes diseases in CF pts, nosocomial infections

neisseria

requires moisture and high concentrations of CO2, oxidase positive, gore on chocolate agar, pathogenic species cause gonorrhea and meningitis

what is the main target for antibiotics

peptidoglycan layer

what causes gill tissue death

karlotoxin 2

BMAA is linked to cause

alzheimer's disease

leginella

gammaproteobacteria, warm water disease such as air conditioners

Enterobacteriaceae

enteric bacteria, gammaproteobacteria, E.coli or noncoliforms such as yersina pests

klebsiella

faculative aerobe, encapsulated, nonmotile, pathogenic species may cause pneumonia, especially in people with alcoholism

legionella grows on

charcoal -buffered yeast extract

pseudomonas

aerobic, versatile, produces yellow and blue pigments, making them appear green in culture, opportunistic antibiotic resistant pathogens may cause wound infections, hospital, and secondary in CF

shigella

nonmotile, dangerously pathogenic, produce shiga toxin, which can destroy cells of GI tract, cause dysentery

deltaproteobacteria

gram negative proteobacteria that includes sulfate reducing bacteria

epsilonproteobacteria

smallest class of proteobacteria, campylobacter and helicobater

campylobacter

aerobic; often infects chickens; may infect humans via undercooked meat, causes severe enteritis

helicobacter

aerobic, bacterium, can damage the inner lining of stomach, causing gastritis, peptic ulcer, and stomach ulcer

bacillus anthraces would not grow in the presence of the related mold

penicillium notatum

trichophyton erinacei

produces B lactam antibiotics as part of the skin microbiome of hedges

trichophyton erinacei tx

azoles (clotrimazole)

What is a key difference between bacteria and cyanobacteria?

bacteria are a key group of infection causing and drug producing organisms while cyanobacteria are a concern regarding environmental toxins

anuranofin and Salvarsan

thiol targeting, elect number of marker proteins, coPR scores similarity to nitrofurantoin

vancomycin

inhibits proteins associated with membrane structural integrity and associated function YeeC+H (stress), YoxD(oxidoreductase) and ABC transporter ATP binding protein

Vancomycin at the atom level

bind to D-Ala-D-Ala preventing cell wall biosynthesis through 5H bonds

how does vancomycin work

reduction of H bonding decreases affinity for bacteria due to less reproduction

phenotype approach

known molecules but unknown targets (most discovered this way)

targeted approach

known target (purified) screen molecule libraries.

drug design approach

known target and use of computer modeling to design ligand. weeks well with protein targets but less effective for other targets (cell membrane)

polypharmacology approach

design drug to act on multiple targets to delay resistance development

Chloramephenicol

inhibits formation of peptide bond

linezolid

prevents formation of the 50/30s ribosomal complex

tetracycline

interfere with binding of tRNA

ahminoglycosides

mRNA codon to be misread

macrolides, clindamycin, streotigramins

block the polypeptide exit tunnel

initiation

RNA polymerase binds to DNA and finds the start sequence. imitation macron protein (IF2) controls entry of tRNA onto ribosome

elongation

EF facilitates formation of the peptide bonds. 20 AA added/second. EF structures are diff between bacteria and eukaryotes but fcn the same. diphtheria toxin and Pa exotoxin act on host EFs

decoding (translation)

reading mRNA and converting to protein

accommodation

key conformational change during transfer RNA selection and allows tRNA into the ribosome

hybrid states

conformational change in ribosome, transitional configuration of tRNA with ribosome during translocation

translocation

movement of mRNA and tRNA from the aminoacyl site to peptide site to exit site of ribosome.

termination and recycling

last step of protein synthesis involving ribosome recycling factor (RRF) and EF-G

daptomycin

treats Gram+ infections, resistance is uncommon

enterococcus faecalis

LiaX a master modulator for resistance

over 2.8 million antibiotic resistant infections occur causing more than

35,000 deaths

peptidoglycan layer consist of

N-actelylglucosmaine, n-actelymuramic acid, and cross linked tetrapeptide chains

nitrofurantoin

-primarily used to tx uncomplicated bladder infections and UTIs

- DO NOT use in kidney issues or pregnancy

fosfomycin

used for bladder infection and occasionally prostate, excreted in the urine

fosfomycin MOA

inhibition of cell wall biogenesis by inactivating MurA. this is mediated by the highly reactive epoxide moiety which alkynes cys 115. This is a unique target to this drug

c. diff S layer

has 28 proteins that may provide unique targets

VRE

cell membrane remodeling mediates resistance

pseudomonas aeruginosa virulence factors

protease, exotoxins, phospholipase, pyocyanin, siderophores, alginate

Erythromycin resistant group A streptococcus (GAS) tx

amoxicillin or azithromycin

mycoplasma genitalium

No cell wall around the membrane means that cell wall targeting antibiotics are not active.

First organism with a synthetic genome named JCV-10

bordatela pertusis

whooping cough

tx: erythromycin and macrolides

Vibrio vulnificus tx

ceftriaxone and doxycycline

Trichophyton erinacei

B lactam antibiotics as part of the hedgehog skin tx azoles

bacteriostatic drugs

Linezolid, clinda, macrolides, tetracyclines

bactericidal drugs

Vanc, fluoroquinolones, B lactams, dapto, aminoglycosides, metronidazole

what causes c diff

clinda, fluoroquinolones, carbapenems, 3rd and 4th cephalosporins

penicillin resistance

blaZ gene

natural penicillins spectrum

syphillis

Antistaphylococcal Penicillins

nafacillin, oxacillin, dicloxacillin

do Antistaphylococcal Penicillins need renal adjustment

NO (D)

aminopenicillins

amoxicillin and ampicillin

what is used to treat endocarditis e. faecalis

ampicillin and ceftriaxone

B lactam/ B lactasse inhibitors

Augmentin, amp/sulbactam, piperacillin/tazobactam

piperacillin/tazobactam only has spectrum for

psuedomonas auerginosa

amp/sulbactam only has spectrum for

acinetobacter

do cephalosporins have activity against MRSA

no, only ceftaroline

do cephalosporins have activity against enterococcus

NO

1st generation cephalosporins

cefazolin, cephalexin, cefadroxil

what are 1st generation cephalosporin spectrum

MSSA, proteus ,e coli, klebsiella, MSSA

3rd generation cephalosporins

ceftriaxone, cefotaxime, ceftazidime, cefdinir, cefpodoxime

what are 3rd generation cephalosporins spectrum?

MSSA (Except ceftazidime) and some enterobacteriales

ceftazidime covers

Pseudomonas aeruginosa (ceftazidime)

ceftriaxone covers

Niesssea gonorrhoeae

what is unique about ceftriaxone about administered

cannot be administered with Ca containing products, given once daly unless meningitis (2x)

what is the spectrum of 4th generation cephalosporins

Strep, MSSA, enterobacteriales, Pseudomonas aeruginosa, ampc

what is an adverse effect of cefepime

neurotoxic

what is an adverse effect of ceftaroline

neutropenia

what is the spectrum of the 5th generation of cephalosporins

Strep, MRSA, enterbacterles

carbpebenems

meropnem and ertapenem

spectrum of carbapenems

Strep, MSSA, most enterobacteriales, AMPc, ESBL, anaerobes

APE (E is the exception)

Acinetobacter, Pseudomonas aeruginosa, enterococcus faecalis all but ertapenem