chapter 9 micro

Synthetic

made in a lab

true antibiotic

• comes from living org

• most antibiotics

semi synthetic

modified true antibiotics

thomas and bretheim

• 1905

• Pioneered early research in chemotherapy, focusing on the use of arsenical dyes

• earliest→learning how to treat disease

• Atoxyl- NOT AN ANTIBIOTIC- arsenical, used to treat African Sleeping Sickness (protists→euk)

• led to blindness

Paul Erlich and Hata

• 1910

• dyes and selective toxicity

• Introduced the concept of "magic bullet" for selectively targeting pathogens, leading to the development of Salvarsan

• Salvarsan is considered 1st antibiotic and used agains Treponema pallidum (Syphillis)

Dogmak, Jacques and Trefouel

• 1935

• Developed Prontosil, which led to the discovery of sulfonamides

• prontosil red (dye) against streptococcal and staphylcoccal infections

  • can bind/kill

  • tried on petri dish and didnt work so tried on his own daughter

  • worked in a living organism→modified due to enzymes and pH

  • off to on position

  • no in vitro→yes in vivo

penicillin

• made by fungus Penicillium

• 1st true antibiotic

ernest duchesne

• 1896

• noticed fungus bc growing next to each other but no contact→zone of inhinition

alexander flemming

• 1928

• microbiologist who is interested but needed help

• noticed fungus is killing bacteria

florey chain and heatley

1939

• recieved nobel peace prixe in 1945

• isolated the compounds penicilin that is being killed by the fungus

• fungus is killing bac due to competition

• WW2→first time soldiers are getting penicilin

• microbes become resisitant from ppl taking when not supposed to

Waksman

First person to identify steptomycin; used streptomycin to treat M. tuberculosis

• multi drug resisitant

• mycobacterium (TB)→mycolic acid

Acinetobacter baumannii

• important to identify bc resistant to all drugs identified before this

• Eskape→hospital acquired

• worst of pathogens

selective toxicity

goal: target pathogens, leave everything else alone

• magic bullet does not exist

therapeutic index

• ratio dose to therapeutic dose

• “just the right zone”

• larger the index, the better the drug

• smaller→narrow amt btwn harm

broad spectrum

• works against many gram - and +

• less specific

narrow spectrum

• works against few gram + or gram -

• more specific

zone of inhibition

• test of antibiotic effectiveness

  • place on agar plate

• if effective: prevents bacterial growth around disk

• the bigger the ZOI, the better the drung—>FALSE

MIC

• minimum inhibitory concentration

• minimum concentration needed to inhibit bacterial growth

• stop replication

• -static

MLC

• minimum lethal concentration

• minimum concentration needed to kill bacteria

• -cidal

• destruction of microbe→ get rid of it

• immuno compromised need this bc they have no immune system

The Kirby-Bauer test (or disk diffusion test) is a test used to see if a bacteria is sensitive to an antibiotic. If it is sensitive, a clear zone will appear called the zone of inhibition.

true

Place the following antimicrobial drugs in order from most to least selectively toxic.

Cell wall synthesis inhibitor

Metabolic antagonist

Protein synthesis inhibitor

Nucleic acid synthesis inhibitor

inhibitors of cell wall synthesis

• most specific but doesnt work for everyone bc not everyone has a cell wall

• do not lyse

• most precise

• least side effects are safer

  • does not work on mycoplasma bc no cell wall

protein synethesis inhibitors

• a lot of steps

• inhibit translation

• ex: mRNA to protein→blocking ribosomes

• no ribo=no protein/polypeptide

metabolic antagonists

• pick a pathway we dont use→inhibit

• ex: folic acid

  • bacteria has it

  • allows us to be more specific

nucleic acid inhibitors

• most side effects

• least specific

• most harmful

• inhibits DNA rep and transcription

• DNA→RNA

penicillins

• bactericidial

• B lactam ring

  • B lactamase (bind and break down B ring)→penicillinase

  • inhibits making of the covalent/peptide bonds

• transpeptidation-peptide bonds btwn NAM and NAG

• Penicillin V and G against gram + only

  • narrow

  • true antibiotic

• semisynthetic- broad spectrum

  • ampicillin- gram -, H. Influenzae, salmonella spp, and s dysentariae

cephalosporins

• 
  Made from fungi Acremonium

• have B lactam ring (inhibits transpeptidation)

• true antibiotic

• broad spec

• used if pt is allergic to penicillin

• bactericidal

carbopenium

• hybrid of penicillin and cephalosporin

• b lactam ring

• semi synthetic

• broad spectrum

vancomycin

• made nby streptomyces (bac)

• narrow

• gram pos

• “drug of last resort”

• to prevent resisitant but bc we used it so often

• VRE-vencomycin resis enterococcus (intensines)

ribosomal subunit

• bacteria =70s

  • 50 s /23s RNA

  • 30s/16sRNA

• euk=80s

  • 40 s -small

  • 60s -large

aminoglycosides

• protein inhibitor

• bactericidal

• narrow

• n=gram negative

• toxic renal damage

• 30s/16s rna -small

tetracyclines

• protein inhibitor

• bacteriostatic

• broad

• 30s

• atypical: rickettsias, chlamydiase, mycoplasma

• 2 true antibiotics: oxytetracycline + chlortetracycline

  • produced by streptomyces spp.

• black teeth

macrolides

• large

• protein I

• bacteriostatic

• broad spectrum

• 50s/23 s

• gram pos, mycoplasma spp and some gram neg

• used for pts allergic to penicillin and cephalosporin

• b lac ring

erythromycin

• true antibiotic

• saccharaorpolyspora

azithromycin

• chalmydia

• z pack

• along w amozicillin for most commonly prescribed

lincosamides

• 50s/23s RNA

• anaerobic microbes

• supports C diff growth

• mainly gram pos some gram negative

• clindamycin-CAMRSA

oxazolidinoses

• bacteriostatic

• broad

• synthetic

• 50s/23s rRNA

• no 70s meaning no translation

• only used in hospitals to prevent resistance

chloramphenicol

• protein

• bacteriostatic

• 1st broad spectrum

• 50S

• against most gram pos, gram neg anaerobes and rickettsisas

• toxic

• aplastic anemia, leukemia, neurotoxins

• grey baby syndrome

• inhibits mitochondiral protein synthesis

• not allowed in food producing animals

sulfonamides/sulfa drugs

• metabolic

• bacteriostatic, broad

• synthetic→inhibits folic acid

• bac grows folic acid

• euk absorb folic acid

• Sulfa drugs are a structural analog to

  PABA. This means it looks similar in structure to this molecule. Because sulfonamides have such similar structure, they are able to compete to the active site of the enzyme dihydropteroate synthase

trimethoprim

• metabolic, static, broad

• inhibt the making of folic acid by inhibiting dihydrofolate reductase

• combined w sulfa drugs t increase efficacy of treatment -bactrim

• abdominal pain and photosensitivity rxns

fluoroquinolones

• nucleic acid, cidal, broad, synthetic

• prevents DNA replication by inhibiting DNA gyrase and topoisomerase 4

  • used to help treat UTIS

• against enteric bac

• cipro

• tendon rupture not given to athletes

rifamycin

• NA, cidal, broad

• rifampin-most used

  • semisynthetic

  • blocks transcription by binding RNA ppol specifically to the B subunit

  • TB and mycobacterial infections

  • meningococcal menigitis or Haemophilus influenzae type B menigitis

  • may cause red sweat and urine

antiviral drugs

• difficult to move/identify bc viruses will use enzymes/all of them for ourselves

• drug development as been slow

• drugs currently used inhibit virus specific enzymes and life cycle processes

antiviral drugs for influenza

• vaccines=best guess

• segmented RNA

• Tamiflu

  • neuraminidase inhibitor→inhibits the binding/entrance→means cannot replicate

  • not a cure for influenza, but shortens course of illness bc it decreases viral load

• Xofluza

  • blocks transcription of actual virus

  • no RNA→no translation

antiviral drugs for herpes

• DNA viruses

  • use their own enzymes to phosphorylate nucleosides→nucleotifes

• analogs that inhibit replication/transcription=end of virus

• acyllovir (blocks replication) and vidarabine

  • A drug used to inhibit Herpesviridae viral replication

nucleosides

sugar and nitrogeneous base

nucleotides

sugar, nitrogen base, phosphate

anti HIV drugs

• most successful in drug cocktail (HAART)

• PrEP- two NRTIs daily ; aheadof time

epculsa and harvoni

A combination drug used to fight Hepatitis C virus

antiviral drugs for hep c

• RNA virus (error prone)

• possible for HIV contraction

• increased in the last decade

• interferon and ribavirin was first used but too many side effects

antifungal drugs

• identifying uniqueness is difficult bc eukaryotic

• fewer effective gagents

  • low therapeutic index and are toxic bc smaller

• easier to treat superficial than systemic

• fungistatic→inhibit

• prefer cooler temps than body heat

superficial mycoses

• topical

• nystatin→ from streptomyces

• bacteria to kill a fungus bc of competition

ex: trush

systemic mycoses

• echinocandins -block synthesis of the cell wall

• inhibits B 1,3, D glucan synthase

other examples:

fluconazole→ low side effects and for immuno comp pts

Fluconazole

A drug used to treat systemic mycoses that has low side effects (anti fungal)

5-flucytosine anti fungal

A drug used to treat systemic mycoses that is a uracil analog that disrupts RNA function

Nystatin anti fungal

A drug used to control superficial candidiasis

Amphotericin B anti fungal

A drug used to treat systemic mycoses that binds to ergosterol in membranes; highly toxic

antiprotozal drugs

euk

• chlroquine→plasmodium (malaria)

• metronidazole- reduced to RNS by Entamoeba (Dysentery) and Trichomonas (vag infections)

• combo therapy: toxoplasma gondii (spon. abortion)

• inhibit folic acid →no purine→no ATP

in order for a drug to be effective

1. needs to be able to reach infection site (systemic vs superficial)

2. pathogen susceptibility (how likely a pathogen is to be inhibiting/killing by drug

3. needs to exceed the pathogen MIC (drug concentration needs to reach or surpass minimum concentration to inhibit/kill pathogens)

drug resistance

• microbes in abscesses or biofilms

  • localized centers/community of bac

  • they reduce penetration

  • biofilms have EPS

• resistance of mutations

  • change in bacterial DNA

mechanisms for drug resistance

• intrinsic or acquired

  1. modify the antibiotic target (if target changes, cant bind)

  2. degrade or alter the antibiotic (B lactase→breaks down B lactum)

  3. decrease antibiotic concentration inside the cell

     • efflux pump pushes

  4. use an alternate pathway or increase target metabolite production

overcoming drug resistance

• educate

• give drugs in approp concentrations

• give a cocktail

• use drugs when only necessary

types of phages

• temperant

  • lysogenic

  • laid back and lurking

  • instead of killing right away, they insert their DNA and chill as a prophage

  • the bac keeps living and dividing→carrying phage DNA w it .

  • The phage can later switch to lytic mode if triggered

• virulent

  • lytic

  • destroy and release

  • infect bac cell, hijack it, replicate, then lyse the host

  • loud and lethal

  • ex: t4 phage infecting E. coli