Intro to Micro Exam 3

Paul Ehrlich

german physician who hypothesized a magic bullet to kill bacteria, came up with a drug and tested on syphilis

alexander fleming

accidental discovery of the zone of inhibition, isolated penicillin for the firs time (WWII)

antibiotic

a substance produced by a microorganism that inhibits the growth of other microorganisms

selective toxicity

a drug that kills the microbe without being toxic to the host

characteristics of the ideal antimicrobial drug

selectively toxic, microbicidal not microbiostatic, relatively soluble, does not lead to drug resistance, remains potent, complements immune activity, remains active in tissues, readily delivered to infection sight, reasonably priced, doesn’t disrupt the host’s health

prophylaxis

use of a drug to prevent infection of a person at risk

antimicrobial chemotherapy

the use of drugs to control infection

antimicrobials

all inclusive term for any microbial drug, regardless of its origin

semisynthetic drugs

drugs that are chemically modified in the laboratory after being isolated from natural sciences

narrow spectrum

antimicrobials effective against a limited array of microbial types

broad spectrum

Antimicrobials effective against a wide variety of microbial types

how to identify which microbe is causing an infection

culturing, rapid tests, and common sense

kirby-bauer test

use discs with antibiotics on plate and measure for zones of inhibition across diameter

therapeutic index

used as a measure of the relative safety of a drug

therapeutic index equation

toxic dose/minimum inhibitory concentration

considerations for in vivo vs in vitro

concentration, resistance, number of pathogens, patient compliance

concentration

works differently on an agar plate than in the body

resistance

infections on the dish could react differently than the infection in the body

number of pathogens

could be multiple kinds of bacteria causing the infection

patient compliance

taking the drug properly, finishing out antibiotics

considerations for the patient’s condition

pre existing conditions, allergies, infants, pregnancies, breastfeeding, elderly, and other drugs

synergistic actions

using two or more different drugs at lower doses instead of one drug alone

genetic or metabolic abnormalities

due to other medications the patient is on, their age, and other conditions they may have

site of infection

effects what kind of administration form of medication the patient will need

the microbiome

oral drugs are chemically modified depending on what microbes are found in the gut

mechanisms of action

inhibit: cell wall synthesis, protein synthesis, plasma membrane, nucleic acid synthesis, synthesis of essential metabolites

inhibiting cell wall synthesis

principle: leads to cell lysis

focus: peptidoglycan layer

type: bactericidal

example: natural and semisynthetic penicillins

natural and semisynthetic penicillins

penicillin V, penicillin G, methicillin, ampicillin, amoxicillin, azlocillin

penicillin V

spectrum of action: narrow

oral

penicillin G

spectrum of action: narrow

injection

methicillin

spectrum of action: narrow

no usually resistant to bacterial enzyme that breaks down penicillin

ampicillin

spectrum of action: broad

works well on gram negative bacteria

amoxicillin

spectrum of action: broad

gram negative infections, good absorption

azlocillin, mezlocillin, ticarcillin

spectrum of action: very broad

low toxicity

beta lactam ring

structure found in almost all penicillins that deactivates the entire penicillin

cephalosporins

beta-lactam drug, bactericidal, broad spectrum

non-beta-lactam ring drugs that still target the cell wall

bacitracin, isoniazid, vancomycin

bacitracin

binds to membrane and prevents bacteria from making peptidoglycan layer

vancomycin

binds to cross links to make cell wall dysfunctional, more potential toxicity to humans, tough on kidneys

inhibiting protein synthesis

focus: bacterial ribosome

generally bacteriostatic

drugs that inhibit protein synthesis

aminoglycosides, chloramphenicol, oxazolidinones, tetracyclines, macrolides,

aminoglycosides

mechanism: bind to 30S ribosome

Spectrum: great against gram negative bacilli

Bactericidal

Examples: streptomycin, gentamicin, and neomycin

chloramphenicol

mechanism: binds to 50S ribosome

Bacteriostatic

can be toxic

oxazolidinones

bind to the ribosome so 2 parts cannot come together

prevent initiation in translation

example: linezolid used against MRSA

tetracyclines

mechanism: blocks the A site of the ribosome

Spectrum: broad, useful against intracellular bacteria

Bacteriostatic

cons: toxicity causes GI issues, and yellowing of teeth

Example: Doxycycline that works against STIs, lyme disease, cholera, and acne

macrolides

mechanism: binds to 50S unit of ribosome

Spectrum: gram positive, mycoplasma, legionella

Bacteriostatic

cons: resistance is very common

Examples: erythromycin and clindamycin

inhibit folic acid synthesis

goal: without folic acid, bacteria die

Selective toxicity: bacteria have to make their own folic acid, can be easily targeted

examples: sulfonamides, trimethoprim, sulfones

sulfonamides

completely synthetic, used against UTIs

trimethoprim

used with sulfonamides

sulfones

used to treat leprosy

injure cytoplasmic membrane

mechanism: detergents

selective toxicity: almost all used topically due to high toxicity

examples: polymyxins in triple antibiotic ointments

inhibit nucleic acid synthesis

goal: inhibit either replication or transcription

most often bactericidal

inhibitors on transcription: difficult target

examples: rifampin

rifampin

bacterial polymerase can be targets to prevent elongation in transcription, very narrow spectrum

inhibit replication

mechanism of action: gyrase enzyme is targeted

problems: unless gyrase is specifically targeted, toxicity crossing could occur due to similarities

examples: nalidixic acid, fluoroquinolones, ciprofloxacin

antifungal drugs

more difficult to treat: fungal cells are eukaryotic therefore stronger

opportunistic infections

opportunistic infections

infections caused by our normal flora when they get into the wrong place, cause problems in immunocompromised patients and those already on antibiotics

fungal cell targets

plasma membranes, fungal cell walls (most selectively toxic target), nucleic acid synthesis

targeting fungal plasma membranes

ergosterol (in fungal membranes), not cholesterol (in human membranes to provide rigidity)

Examples: Macrolide Peptide (Amphotericin B), Azoles (Clotrimazole, Ketoconazole)

targeting fungal cell walls

most selectively toxic target

Example: Echinocandins

targeting fungal nucleic acid synthesis

fungi and human processes almost identical

Example: Flucytosine added to DNA instead of Cytosine

antiprotozoan drugs

quinine and metronidazole

quinine

only targets certain species of malaria parasites, used in combination therapy, damages DNA

metronidazole

interferes with metabolism, works against parasite that infects the liver, damages DNA

antihelminthic drugs

some of the most difficult microbes to treat, drugs stop reproduction of worms, examples: Mebendazole, Albendazole, and Paralytics

mebendazole

work by inhibiting glucose processing in the worms

albendazole

work by inhibiting glucose processing in the worms

paralytics

other drugs that paralyze the worm, makes them unable to attach

antimicrobial resistance

an adaptive response that occurs so that microbes develop tolerances to drugs that would normally be lethal

mechanisms of resistance

mutations and horizontal gene transfer

5 modes of resistance through horizontal gene transfer

new enzymes that deactivate the drug

blocked penetration

efflux pump

target modification

inactivate enzymes

new enzymes that deactivate the drug

betalactamase: cleave the active chemicals

blocked penetration

DNA mutations alter the surface of the bacteria to block the drug

efflux pump

pump made by the bacteria that pumps the drugs out immediately

target modification

binding sites for drugs are blocked, occurs through mutation or new genes

inactivate enzymes

a metabolic pathway is shut down or an alternative pathways is used to make enzymes

alternatives to antibiotics

defense peptides, bacteriophages, RNAi (interference), normal flora

how to prevent drug resistance

limit drug use

proper drug use

narrow spectrum antibiotics

multiple drug treatments

limit exposure to antibiotics

4 steps to antibiotic resistance

1. lots of bacteria, few are drug resistant

2. antibiotics kill bacteria causing the illness, as well as the good bacteria protecting the body from infection

3. the drug resistance bacteria are now allowed to grow and take over

4. some bacteria give their resistance to other bacteria, causing more problems

3 major reactions to drugs

1. damage to tissue through toxicity

2. allergic reaction

3. disruption to microbiota

direct damage to tissue through toxicity

happens directly because of the drug or from a byproduct of the drug

allergic reactions

most common is penicillin, have been reported for every antibiotic

disruption to microbiota

superinfections: most often yeast infections, can be very severe or life threatening

viruses

acellular, obligate intracellular parasite, very small, don’t follow the rules of life

how viruses don’t follow the rules of life

can’t reproduce without a host cell, lack enzymes needed for reproduction, don’t have enzymes or proteins for metabolic functions

virion

a complete viral particle

capsid

outside covering of a viral particle; made up of repeating subunits called capsomeres

additional enzymes

reverse transcriptase

viral shapes

helical, polyhedral, and complex (can be enveloped or naked)

viral genome

can be either DNA or RNA

6 stages of replication

attachment, penetration, uncoating, replication, assembly, release

attachment

a virus fuses to the host cell surface

host-range

the cells the virus has the ability to effect

penetration

the virus enters the cell through endocytosis

uncoating

viral DNA is formed by reverse transcription

replication

the DNA is transported across the nucleus and integrates into the host DNA (RNA happens in cytoplasm)

assembly

new viral RNA is used as genomic DNA and to make new proteins

release

new viral RNA and proteins move to the cell surfaces and a new, immature viral cell forms

methods of viral release

budding and lysis

viral effects on host cells

cytocidal infection, cytopathic effects, and DNA damage and cancer

cytocidal infection

infections that kill the host cell