MLS 2214 Exam 1

Unit 4, 5 and 6

What is an antimicrobial?

A chemical that kills or inhibits a disease causing organism

What’s the difference in the cell membrane between eukaryotes and prokaryotes?

Cholesterol

What is an antibiotic?

A metabolic product of mold or bacteria

What is a synthetic drug?

Chemical drugs that are manufactured

What are semi-synthetic drugs

Antibiotics that have been chemically modified, most antimicrobials modernly are semi-synthetic

What is selective toxicity

1. Effectively kills or inhibits an organism AND

2. has no side effect to the host

What does selective toxicity target in bacteria?

The differences in prokaryotes and eukaryotes

What are the differences between prokaryotes and eukaryotes

• Eukaryotes have a nucleus while prokaryotes don’t

• Eukaryotes have cell bound organelles while prokaryotes don’t

• Prokaryotes have a cell well (peptidoglycan) while eukaryotes don’t

• Eukaryotes have 80s ribosome (60s+40s) and prokaryotes have 70s ribosome (50s+30s)

Why is the presence of a cell wall so important when it comes to antimicrobials?

It allows for something that antimicrobials can attack against that do not exist in eukaryotic cells, the peptidoglycan layer

What does s stand for in 40s and 60s

Svedburg unit, a measurement of the sedimentation rate in an ultracentrifuge. When two ribosomal subunits are combined they sediment at a faster rate than when alone

Explain selective toxicity in regards to fungus and parasites

Funus and parasites are cells that

Define narrow spectrum antibiotics

• Effects only specific type of organism

• Best used when causative agent is known

Define broad spectrum antibiotics

• Effects wide range of organisms

• used when causative agent is unknown

How do super infections happen?

Antimicrobials kill off susceptible normal flora and so opportunistic pathogens are able to grow and cause infection due to lack on competition

What are the effects of broad spectrum antibiotics on normal flora?

• Wipes out all normal flora that susceptible

• Creates a lack of competition - E. coli

• Can result in a super infection from opportunistic pathogens

What are some examples of super infections

• Ear infections - dirrhea

• Yeast infections - skin rashes and vaginitis

• Antibiotic associated enteritis - C. diff

Define susceptible, sensitive

An organism is inhibited or killed

Define resistant

The antimicrobial has no effect on the

Define MIC

The lowest concentration of a drug required to inhibit an organism

Define MBC

• Minimum bactericidal concentration

• The minimum concentration of a drug required to kill an organism

Define bacteriostatic

Suppresses an organism’s growth, if the drug is removed then the organism will continue to grow

Define bactericidal

The drug makes an irreversible lethal effect and kills the bacteria

Define broth dilution test

A method used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of an antimicrobial agent by diluting it in a liquid growth medium.

Define anaphylactic shock

A severe, life-threatening allergic reaction characterized by rapid onset, often involving difficulty breathing, swelling, and a drop in blood pressure. It requires immediate medical attention and intervention.

Define probiotics

Probiotics are live microorganisms, usually bacteria or yeast, that provide health benefits when consumed in adequate amounts. They help maintain a healthy balance of gut microbiota and can support immune function.

What are the 6 modes of antimicrobial action?

• Inhibition of cell wall synthesis

• Inhibition of cell membrane synthesis

• Inhibition of protein synthesis

• Inhibition of nucleic acid synthesis

• Inhibition of metabolic pathways

• Inhibition of recognition or attachment

What drugs work by inhibiting cell wall synthesis?

• Penicillin

• ethambutol

• echinocandins

• carbapenems

• cycloserine

• Cephalosporins

• Vancomycin

• isoniazid

• monobactams

• bacitracin

How do penicillins, cephalosporins, vancomycin, monobactams and carbapenems work?

They inhibit bacterial cell wall synthesis

What are the two steps that are blocked in cell wall synthesis

• Blocks the final step in cross linking of the peptidoglycan mesh

• Blocks early peptidoglycan synthesis

What drugs work by blocking the final steps in cross linking of the peptidoglycan mesh?

• Penicillin

• Cephalosporins

How do penicliins’s and cephalosporins work?

work by blocking the final steps in cross linking of the peptidoglycan mesh

What drugs work by blocking the early steps in peptidoglycan synthesis?

• Vancomycin

• Cycloserine

• Bacitracin (Neosporin)

How do vancomycin, cycloserine, and bacitracin work?

work by blocking the early steps in peptidoglycan synthesis

What is transpeptidase?

• An enzyme involved in the cross-linking of peptidoglycan layers in bacterial cell walls, crucial for maintaining structural integrity

• Convert the peptide chain from nag to nam

What are penicillin binding proteins

• A group of proteins that bind penicillin and are important for the synthesis and maintenance of the bacterial cell wall, particularly in peptidoglycan cross-linking.

Whats another term for transpeptidase?

Penicillin-binding protein

How do drugs work by blocking the final steps in cross linking of the peptidoglycan mesh?

They bond to the transpeptidase enzymes which stop the cross linking

How do drugs work by blocking the early steps in peptidoglycan synthesis?

• They interfere with enzymes used in the transfer of building blocks to cell wall from cytoplasm

• Prevent peptide crossbridge from being made

What are the first two antimicrobial drugs that were put into large scale production?

• Sulfa drugs

• Penicillin

What are the disadvantages of Penicillin G

• Most stable, but unstable in acidic solutions - cannot be taken orally

• Only effective against gram pos

• Not effective against penicillinase

What structure is this?

Beta lactam ring

What enzymes can break down the beta lactam ring?

Penicillinase or beta lactamase

What is the end product of a Beta lactam ring that has been broken down?

Penicilloic acid, which is inactive against bacteria.

What is the difference between Penicillin G and Penicillin V?

• Penicillin G is more effective against gram-positive bacteria and must be given via injection

• Penicillin V is more stable in acidic environments, allowing for oral administration.

What are the advantages of using ampicillin

It is broad spectrum and acid resistant

What are the advantages of using ticarcillin?

More actively used against GNRs like pseudomonas but not as effective against some gram pos organisms

What are the common beta lactam antimicrobials?

• Penicillin

• Cephalosporins

• Monobactams

• Carbapenems

What class of antibiotics are penicillin, cephalosporins, monobactams, and carbapenems?

Beta lactam antibiotics

What are some examples of penicillins

Penicillin G, Penicillin V, methicillin, dicloxacillin, ampicillin, amoxicillin, ticarcillin and piperacillin

How are cephalosporins classified

• Classified by the generation they were made

• Newer generations have more effectiveness against GNRs and beta lactamase producers

What is an example of a monobactam?

Aztreonam

What is an example of a carbapenem

Imipenem

What is impenem an example of?

a carbapenem antibiotic

What is the broadest antimicrobial?

Imipenem

Why should imipenem only be used in emergencies?

Because it is so broad it will kill off NF and may lead to resistant infections

What are beta lactamase inhibitors?

• Have a high affinity for beta lactamase

• Best used in combo with B lactam drugs

  • Clavulanic acid

    • Amoxicillin + clavulanate

    • Ticarcillin + clavulanate

How do antimicrobials inhibit the synthesis of the cell membrane?

• Attaches to phospholipids

• Combines with sterols (cholesterol)

Why do antimicrobials inhibit the synthesis of the cell membrane work?

They increase the permeability and reduce the osmotic integrity of the plasma membrane

Why is the selective toxicity low for cell membrane synthesis inhibitors?

• Because they are only used as topical treatment and not used orally

• Eukaryotes have a cell membrane with minimal differences from prokaryotes

What are some examples of antimicrobials that inhibit cell membrane synthesis

• Polymyxin B

• Bacitracin

• Ergosterol

• Azoles

How do polymyxin B, bacitracin, ergosterol and azoles work?

Inhibit cell membrane synthesis

Where is ergosterol found?

In fungal cell membranes.

Why does ergosterol increase selective toxicity of amphotericin B?

Because amphotericin binds selectively to ergosterol in fungal membranes, disrupting their integrity without affecting human cell membranes that contain cholesterol

How do antimicrobials that inhibit protein synthesis work?

• Bind to the 50S subunit or bind to the 30S subunit

How does an antimicrobial that binds to the 50S subunit work?

• Inhibits the formation of peptide bonds in growing poly peptide chains

• Inhibits peptide chain elongation

What antimicrobial inhibits the formation of peptide bonds in growing poly peptide chain?

Chloramphenicol

What antibiotic inhibits peptide chain elongation?

• -rythromycin

• Azithromycin

• Linezolid

How do azithromycin, linezolid and -rythromycin work?

They inhibit peptide chain elongation during protein synthesis.

How do antimicrobials that attach to the 30S subunit work?

• Interferes with the attachment of tRNA

• Causes misreading of mRNA by changing the shape of 30S

What is an antimicrobial that interferes with the attachment of tRNA

Tetracycline

How does tetracycline work?

It inhibits protein synthesis by preventing the attachment of tRNA to the ribosome.

What are antimicrobials that cause a misreading of mRNA by changing the shape of the 30S

• Aminoglycosides

  • Streptomycin, gentamicin, neomycin, tobramycin, amikacin

How do aminoglycosides work?

cause a misreading of mRNA by changing the shape of the 30S

How do nucleic acid synthesis inhibitors work?

• Targets enzymes or precursors used in DNA and RNA synthesis

• Selective toxicity is limited to slight differences between prokaryotes and eukaryotes

How does polymerase work?

• An enzyme that synthesizes DNA and RNA

• The antimicrobial target mRNA synthesis

What antibiotic targets mRNA synthesis

• Rifampin

• R N A

How does rifampin work?

Rifampin works by inhibiting RNA polymerase, preventing bacterial RNA synthesis, which ultimately stops bacterial growth.

What is topoisomerase and DNA gyrase

• Topoisomerase - helps unwind DNA and RNA

• DNA gyrase - winds DNA back into a super coil

What antibiotics target topoisomerase and DNA gyrase?

• Quinolones + nalidixic acid

• Fluroquinolones

  • Ciprofloxacin, floxacin, norfloxacin, ofloxacin, and levofloxacin

How do quinolones and fluoroquinolones work?

Quinolones and fluroquinolones work by inhibiting bacterial DNA gyrase and topoisomerase IV, leading to interference with DNA replication and transcription

What antibiotics work by targeting nucleotide analogs?

• Flucytosine - antifungal

How does flucytosine work?

It blocks the ability to create uracil in RNA

What are the modes of action in antimicrobials that inhibit the metabolic pathway

• Is a competitive analogue to PABA (Para amino benzoic acid)

• Competitive analogue to dihydrofolic acid

Where to bacteria get their folic acid?

They synthesize it themselves

What are the steps in the folic acid pathway?

1. PABA

2. Dihydrofolic acid

3. Tetrahydrofolic acid

4. Purine and pyrimidine nucleotides

5. DNA and RNA

What drugs compete and PABA?

Sulfonamides

What drugs compete with dihydrofolic acid

Trimethoprim used with Sulfamethoxazole

What are two genetic changes that can lead to drug resistance?

• Chromosome mediated resistance

• Transfer of genetic material

Define transformation?

A recipient cell takes up DNA from the environment

Define conjugation?

A fertility plasmid forms a conjugation pili that attaches to another cell and transfers genes

Define transduction

DNA is transferred from one cell to another via a virus

What is plasmid mediated resistance

An extra chromosomal DNA part has a gene that codes for higher resistance

What is MRSA

Methicillin-resistant Staphylococcus aureus

What is ORSA

Oxacillin-resistant Staphylococcus aureus

What is VRSA

Vancomycin-resistant Staphylococcus aureus

What is VISA

Vancomycin-intermediate Staphylococcus aureus

What is VRSE

Vancomycin-resistant Staphylococcus epidermidis

What is VRE

Vancomycin-resistant Enterococcus

What is CRAB

Carbapenem-resistant Acinetobacter baumannii

What is MDR TB

Multidrug-resistant tuberculosis