Micro Antibiotics

Where do antibiotics classically come from?

Other bacteria and fungi that secrete the antibiotics as a form of cell warfare

What are the three basic factors to be considered when prescribing a drug?

1. The identity of the microbe

2. The sensitivity of the microbe to drugs

3. The overall condition of the patient

What is selective toxicity?

Drug kills only what it is intended to kill

What is the therapeutic dose?

drug level required for clinical treatment

What is a toxic dose?

drug level at which drug becomes too toxic for patient

What is the therapeutic index? How is it calculated?

The comparison of therapeutic and toxic doses. Toxic dose/therapeutic dose = index

Is a higher or lower therapeutic index better?

higher

What is the minimal inhibitory concentration?

Lowest concentration of a chemical that prevents VISIBLE growth of a bacteria

What is the minimal lethal concentration?

lowest concentration of drug that completely KILLS pathogen

Why might we want to use an inhibitory drug as opposed to a lethal one?

• less likely to kill good bacteria

• encourages the hosts immune response instead of doing the work for it

What broth is used for MIC and MLC dilution tests?

Mueller-hinton

How do you interpret a dilution susceptibility test?

The first concentration with no visible growth is the MIC. Using that MIC broth, inoculate a tube with greater concentrations of the antibiotic. The next tube with no visible growth is the MLC.

What is another name for the disk diffusion susceptibility test?

Kirby-bauer test

What agar is used for a Kirby-Bauer test?

Mueller-Hinton

What is an ETest?

uses plastic strips with a concentration gradient of an antibiotic. after incubation the MIC can be read by observing where the growth intersects the strip.

What are the three susceptibility tests for antibiotics?

Dilution, Kirby-Bauer/disk diffusion, Etest

What are the three ways to classify antimicrobials?

Origin, spectrum, efficacy

What are the three ways to classify a drug by origin?

Naturally produced, synthetic, semisynthetic

What are the three ways to classify a drug based on spectrum?

Broad, narrow, or something specific such as antiviral or antifungal

What are the two ways to classify a drug based on efficacy?

Cidal or Static

What is the common suffix among cell-wall-inhibiting antibiotics?

-cillin

What structure in cell wall inhibitors allow them to work?

Beta-lactam rings

How do Beta-lactam rings work?

They closely resemble D-alanine which is an essential amino acid in the cell wall. Cell wall enzymes bind to the -cillin instead of d-alanine.

Other than -cillins, what is the other name for cell wall-inhibiting antimicrobial?

cephalosporins (they still work the same way)

What are three examples of cell wall inhibitors that arent -cillins or cephalosporins?

1. Vancomycin - blocks D-ala binding

2. Bacitracin

3. Isoniazid - interfers with mycolic acid

What drugs target the cell membrane?

Polymyxins

Why might polymixins be administered topically?

These drugs are toxic, but skin cells are already dead!

Why are protein synthesis interfering drugs broad spectrum?

All microbes make proteins

What drugs target the small ribosomal subunit?

Aminoglycosides and tetracyclines

What drugs target the large ribosomal subunit?

Chloramphenicol and Macrolides

What drugs target DNA and RNA?

Fluoroquinolones (interferes with replication fork) and rifamycin (blocks trancription)

What drugs are metabolic pathway inhibitors?

sulfanomides/sulfadrugs and trimethoprim

What do sulfadrugs do? Why are they not toxic to humans?

They block folic acid synthesis (essential to make DNA). Human obtain folic acid from our diet, we don't synthesize it.

Antifungals are usually static or cidal?

static

Why is it difficult to fight fungal infections?

Fungi are eukaryotes like humans so our cells are more similar

What are the two classes of antifungals?

polyenes and azoles

What is the difference between polyenes and azoles?

polyenes directly bind to ergosterol

azoles block ergosterol synthesis

What is ergosterol?

the sterol that makes up the fungal cell wall

Antifungals target what part of the cell?

the membrane as they target ergosterol

What are the four types of mycoses?

superficial, subcutaneous, systemic, opportunistic

Why is it difficult to treat viruses? What is targeting when treating a virus?

It is hard to target the virus and not the host, so the viruses multiplication cycle is targeted

What are the three kinds of drug resistance? What is each?

Intrinsic: built in

Acquired: mutated or gained via gene transfer

Drug tolerant: no mechanism of resistance but ignore drug either by bring in a bio film or growing super slow

What are the five mechanisms of drug resistance?

1. Enzymes deactivate drug

2. Decreased permeability/uptake

3. Efflux pump

4. Binding sites/affinity is decreased

5. The targeted metabolic pathway is shutdown/worked around

What causes antimicrobial drug resistance?

overuse, misuse, and abuse of antibiotics

What are the three types of side effects?

1. damage to tissues

2. allergic reaction

3. disruption in normal flora

What is a superinfection?

new infection arising while a patent is receiving abx for the original infection. Typical residents are destroyed causing other microbes to grow unchecked.

Polymixins damage the cell membrane by targetting?

phospholipids

What are the three types of work? Describe them.

Chemical work: anabolism

Transport work: uptake of nutrients, ion balancing

Mechanical work: Movement of the cell (flagella), partitioning chromosomes

The change in energy in a cell is equal to?

The change in enthalpy(heat). Delta G/E = Delta H

What is Gibbs free energy? What is entropy?

Gibbs - The energy associated with a chemical reaction that can be used to do work.

Entropy - The disorder in a system

Know exergonic, endergonic, spontaneous, non-spontaneous

Positive delta G = nonspontaneous, endergonic, requires energy (Typically endothermic)

Negative delta G = spontaneous, exergonic, releases energy (typically exothermic)

What are redox reactions? Why are they important to metabolism?

When one molecule is oxidized and another is reduced, this is important because this is how electron carriers are made

More electronegative molecule (very negative e0) are more or less likely to DONATE an electron?

More likely. Electrons are negatively charged so negative molecules will want to donate them, not accept them.

In bacterial and archaeal cells, where does the ETC occur?

The internal and plasma membranes

What is reduction? What is oxidation?

Reduction is the gain of electrons

Oxidation is the loss of electrons

What molecules in the ETC will have a greater e0, which will have lesser values?

The initial donors (NADH FADH) will be the most negative. LAter acceptors will be the most positive.

Does anabolism or catabolism require energy?

Anabolism requires energy, catabolism releases energy.. (counter intuitive when considering breaking bonds requires energy, but its because more stable bonds are formed in catabolism which releases energy)

What is substrate level phosphorylation?

Transfer of a phosphate group directly from a substrate to ADP

What is oxidative phosphorylation?

series of redox reactions occurring during respiratory pathway (ETC)

Why use ATP as our primary energy source?

It has a very negative delta G when releasing its phosphate group, which it is very happy to do

What does it mean for a pathway to be amphibolic?

It can be both anabolic and catabolic

What are the three primary catabolic pathways?

1. aerobic respiration

2. anaerobic respiration

3. fermentation

What are the four main stages of respiration?

Glycolysis, transition step, krebs/tca cycle, ETC

What does glycolysis start with? What does it end with?

Start: 1 glucose

Ends: 2 NADH, 2 ATP, 2 Pyruvate

Glycolysis produces 4 ATP, but only nets 2 ATP. Why?

2 ATP is invested to phosphorylate glucose

The first step of glycolysis is an example of ___, because?

Group translocation because glucose is brought across the membrane and converted to G6P.

How is glycolysis regulated?

feedback inhibition. PEP (the final intermediate before pyruvate) inhibits Phosphofructokinase (PFK, adds the second phosphate to the fructose)

Substrate level phosphorylation occurs in which step(s) of respiration?

Glycolysis and the TCA

What does the transition step start with? What does it end with?

Starts: 2 pyruvate

Ends: 2 acetyl coA, 2 NADH, 2 CO2

What does the TCA cycle start with? What does it end with?

Starts: 2 acetyl coA

Ends: 6 NADH, 2 FADH, 2 ATP, 4 CO2

(This is per GLUCOSE. Half these to find per acetyl coA)

1 glucose "spins" the krebs cycle how many times?

2, because 1 glucose makes 2 acetyl coA

How many H+ make one ATP?

4

How many complexes are in the ATC?

4, then ATP synthase