Microbiology CH 10 - Antimicrobial Treatments Flashcards
What is a compound that can be used to kill or prevent the growth of one or more microorganisms called?
Antimicrobial
Antimicrobial includes what 4 compounds?
- Antibiotics
- Antifungals
- Antihelminthics
- Antiprotozoans
What do antibiotics target?
Bacteria
What do antifungals target?
Fungi
What do anthelminthics target?
Worms
What do antiprotozoans target?
Parasitic protists
What is the goal of antimicrobial chemotherapy?
To administer a drug that will target the infectious organism without harming the host
What are the 9 parts to the nonexistent ‘ideal’ microbial?
- Toxic to the microbe but nontoxic to host cells
- Relatively soluble; functions even when highly diluted in body fluids
- Remains potent long enough to act and is not broken down or excreted prematurely
- Does not lead to the development of antimicrobial resistance
- Complements or assists the activities of the host’s defenses
- Remains active in tissues and body fluids
- Readily delivered to the site of infection
- Reasonably priced
- Does not disrupt the host’s health by causing allergies or predisposing the host to other infections
Can antimicrobial compounds be found throughout nature?
Yes
Name 2 BACTERIA species that can produce antimicrobial compounds
- Streptomyces
- Bacillus
Name an animal that can produce antimicrobial compounds
Frogs
Name 2 FUNGI species that can produce antimicrobial compounds
- Penicillin
- Cephalosporin
What are made in labs to mimic natural antimicrobials?
Synthetic Drugs
What is made by chemically modifying naturally-occurring compounds?
Semisynthetic Drugs
What 3 things must be known before using antimicrobials?
- Identity of organism
- Organism’s susceptibility to various drugs
- Condition of the infected individual
What are the 3 ways to identify microbes?
- DNA Sequencing
- Staining, morphology, and physiology
- Advanced identification technologies such as Mass-Spectrometry
What are the 3 steps to the Kirby Bauer Technique?
- Bacteria is inoculated on general media, then premeasured antibiotics are placed on media
- Measure zone of inhibition
- Compare each antimicrobial’s zone of inhibition to a table of standards
What is the table of standards used for SPECIFICALLY within the Kirby Bauer Technique?
Identify which antimicrobials an organisms is Resistant (R) or Sensitive (S) to
What is the zone of inhibition?
Space around disc where the organism did not grow
What can you determine by adding various amounts of an antimicrobial to different broth cultures?
Minimum Inhibitory Concentration (MIC) for a particular organism-antimicrobial pairing
Why may there be a different between antimicrobial sensitivity in-vitro (in test tube) and in-vivo(in a living host)?
Different compounds may get metabolized differently by the body
What is the ratio of how toxic to humans an antimicrobial is compared to the minimum effective dose?
Therapeutic Index (TI)
What does lower TI vs higher TI mean?
Lower TI - Drug is less effective, more risky to use
Higher TI - More effective, potentially more ideal for use in a patient
Different patient conditions can affect which drug is better to use. True or False?
True
What is something you’d want to consider in antimicrobial treatments?
HINT: Pertaining to amount
Intent to target small or large number of different microbes
Why would you want to get rid of specific bacteria, but keep the rest?
You may not want to disrupt the natural healthy microbiome
What are antibiotics with a wide range of targets called?
Broad-Spectrum Antibiotics
What are antibiotics with a small range of targets or organisms called?
Narrow-Spectrum Antibiotics
When is a Broad-Spectrum Antibiotic likely to be used?
Frequently used without properly identifying the organism, because the antibiotic is likely to kill whatever it is
When is a Narrow-Spectrum Antibiotic likely to be used?
More effective on specific organisms, but requires more knowledge of specific infections
What is the ‘ideal’ antimicrobial? (NOT all 9 of its qualities)
Selectively toxic, meaning it only acts on bad bacteria
What are antibiotics abbreviated as?
Abx
What are the 5 targets of antibiotics?
- Cell wall synthesis
- DNA Structure and Function
- Protein synthesis
- Cytoplasmic membrane structure and function
- Folic acid synthesis
What does not exist in human cells and is a good target for antimicrobial drugs?
Peptidoglycan
What are Beta-Lactams?
Class of antibiotics that specifically target the process of cell wall synthesis and repair
What are enzymes that are bound by penicillin and other beta-lactams called?
Penicillin-Binding Proteins (PBPs)
What kind of inhibitor is a Beta-Lactam? Why?
Competitive Inhibitor
Prevents creation of peptide bridges in the last step of peptidoglycan synthesis
What is cell division like with vs without Beta-Lactams?
With: Expanding cell wall does not fully connect, so cell growth spills out of cell wall
Without: Cell wall construction proceeds and each cellular division occurs normally
What is the most famous Beta-Lactam?
Penicillin
What are Abx from the Penicillin family paired with? Why?
Clavulanic Acid
Increases efficacy of penicillins in bacteria that are naturally resistant
What is the combination of clavulanic acid and Amoxicillin called?
Clavamox
Name 2 groups of Beta-Lactams
- Penicillin-Binding Proteins (PBPs)
- Cephalosporins
How are Cephalosporins sometimes classified?
‘Generation’ - Based on discovery timeline
How are newer generations of Cephalosporins better? How are they worse?
Increased efficacy against gram-negative organisms
Decreased efficacy against gram-positives (sometimes)
What is a commonly used drug that can be used to treat skin infections called?
Bacitracin
Bacitracin is NOT one of the ingredients in Neosporin. True or False?
False
What treats Staphylococcus infections that are resistant to penicillin and methicillin, or in patients allergic to penicillin?
Vancomycin
Vancomycin targets a ______ _______ in peptidoglycan synthesis
different enzyme
What is Vancomycin commonly used against?
Methicillin Resistant Staphylococcus aureus (MRSA)
What is used to treat Mycobacterium tuberculosis infections? Is its target peptidoglycan?
Isoniazid; No
What does Isoniazid do?
Stops synthesis of Mycolic Acid
Isoniazid is _____________ in rapid-growing Mycobacterium populations. Isoniazid is _____________ in slow-growing Mycobacterium populations.
Bactericidal; Bacteriostatic
Is Isoniazid Broad or Narrow Spectrum? Why?
Narrow Spectrum as it targets Mycobacterium, regardless of the two effects it can produce
Are our ribosomes different from bacterial ribosomes?
Yes
What are 2 important factors to consider when it comes to Protein Synthesis Blockers?
- Only bacterial processes are blocked
- Find things that target bacterial ribosomal subunits
What are 3 steps of protein synthesis that can be targetted?
- Correct “reading” of RNA codons
- Attachments of tRNAs as they enter the ribosomes
- Movement of the ribosome along the mRNA
Name 2 Protein Synthesis Blockers
- Aminoglycosides
- Macrolides
Name 1 Aminoglycoside
Streptomycin
What do Aminoglycosides do?
Attach to ribosomal subunit
When an Aminoglycoside attaches to a ribosomal subunit, what 3 things can it cause the ribosome to do?
- Prevents it from fully assembling or causes it to assemble into a slightly-wrong shape
- Can make it different to transfer growing polypeptide, leading to an incomplete protein
- Can cause misreading of the mRNA, which causes bacteria to produce ‘wrong’ proteins
What kind of antibiotics are targeted by Aminoglycosides?
Gram-negative rods
What blocks the ‘entry’ of tRNA to the ribosome?
Tetracycline
When tRNA entrance is blocked to the ribosomes, what occurs?
Protein synthesis slows down or stops
Name 2 Macrolides
- Erythromycin
- Azithromycin
What do Macrolides bind to?
50S Ribosomal Subunit
What 2 steps do Macrolides block?
- Blocks movement of ribosome along the mRNA
- Blocks transfer of growing polypeptide from one tRNA to the next
When a Macrolide successfully blocks a step, what happens to translation?
Translation slows down or stops
What TYPE of antibiotic is a macrolide? Is it reversible?
Bacteriostatic; Yes, it’s reversible
What is an intermediate in the synthesis of Nitrogenous Bases and certain Amino Acids?
Folic acid (Folate or Vitamin B9)
What is necessary for DNA and RNA production?
Folic acid
What are competitive inhibitors to enzymes in the Folic Acid synthesis pathway?
Sulfonamides
What can inhibiting folic acid biosynthesis lead to?
Slowdown or total stop of cell cycle and cellular processes
Sulfonamides block what processes? What does it not block?
Bacterial, NOT human processes
What targets DNA unwinding enzymes?
Fluoroquinolones
Provide 1 example of a DNA unwinding enzyme
Gyrase
What happens when a DNA unwinding enzyme is targeted by a Fluoroquinolone? Is this process bactericidal or bacteriostatic?
DNA Replication cannot occur; Bactericidal
A Fluoroquinolone’s effects vary in _____________ bacteria and _____________ bacteria
Gram-positive & Gram-negative
Name 1 Fluoroquinolone
Ciprofloxacin
What inhibits bacterial RNA Polymerase?
Rifampin
When RNA Polymerase in bacteria is inhibited, what occurs?
Elongation in transcription never happens past 2nd or 3rd nucleotide, so no usable mRNA is made
Why is Rifampin not used against Gram-Negative bacteria?
Does not pass through outer membrane effectively
What antibiotic interacts with membrane phospholipids?
Polymyxin
When Polymyxin is used, what ends up occurring in cells?
Distortion of cell shape and causes leakage of cytosol
What kind of bacteria is Polymyxin particularly effective against? Why?
Gram-negative bacteria
Rely on membrane for shape and stability
What kind of bacteria can MAKE Polymyxin? It’s another ingredient in ____________
Gram-positive bacteria; Neosporin
List 3 reasons why non-bacterial infections are more challenging to treat than bacterial ones
- Fewer Broad-Spectrum strategies, since infectious organisms may be completely different from each other
- Most research has been done on anti-bacterial treatments
- Are Eukaryotic infections, so higher risk of damaging human processes
In antifungals, what do macrolide polyenes bind to?
Steroids on fungal membranes
When antifungals macrolide polyenes are binded to steroids, what occurs within the cells?
Fungal membranes are more fluid causing leakage of potassium and sodium ions
The steroids that antifungal macrolide polyenes bind to is the same kind as in human cells. True or False?
False
What inhibits the enzymatic pathway that makes fungal steroids? What happens to the fungi?
Azoles and Allylamines
Fungi can’t grow
What inhibits cell wall synthesis in fungi? What are fungal cell walls made of?
Echinocandins; Chitin
Does Chitin appear in humans?
No
What is a key group of drugs used to combat malaria that are derived from bark of certain trees?
Quinines
Quinine molecules are bitter and historically very effective at __________ malaria
Preventing
What is another antimalarial drug that is NOT Quinines? It was used for centuries by what culture?
Artemisinin; Chinese medicine
The discovery of Artemisinin earned who a Nobel Prize in medicine in 2015?
Tu Youyou
What is the main challenge of antihelminthic drugs?
Helminths are not single-celled organisms
What are the 2 MAIN targets for antihelminthic drugs? What occurs when these targets are affected?
- Worm musculature (Pyrantel) - Worm can’t hold on to your digestive tract and is expelled
- Worm’s cell membrane (Ivermectin) - Causes paralysis in the worm
What is an alternative target to the main 2 in antihelminthic drugs?
Targets worm’s symbiotic bacteria
What is a naturally occurring phenomenon that is an emerging challenge in clinical settings?
Antibiotic resistance
What are 2 ways that bacteria have antibiotic resistance?
- Antibiotics can be produced by bacteria, which must be resistant to those same compounds
- Some have naturally-occurring resistance, while some develop a resistance
Some organisms develop or acquire new __________ that help them ______________ or ______________
Enzymes; Deactivate or break down drugs
What are enzymes that break down compounds like Penicillin?
Beta-Lactamases
If an organism can change its _____________, what happens to drugs?
Permeability; drugs may be less able to go in and affect cellular function
Why do changes in bacterial permeability occur frequently?
Mutation in receptor proteins
Organisms can acquire ___________, which will do what?
New proteins; pump drug out of the cell after it comes in, preventing it from affecting cellular functions
____________ for drugs can ____________________________________________________
HINT: Where drugs attach to
Binding sites; change due to mutation, meaning target may no longer be susceptible
How can a bacteria circumvent a drug’s target? What happens when these are used?
Alternative pathways can be used
Ex: If Folic acid can NOW be synthesized, sulfa drugs will no longer work
How do antibiotic resistances arise? It is especially true for what kind of drug?
Mutation can change bacteria’s proteins just enough to make an antibiotic not function
Especially true for drugs that target enzyme’s active site
What is the process in which bacteria can acquire new genes called?
Horizontal Gene Transfer
What happens once a bacteria has the ability to resist a drug exists? Over a short period of what time, what happens to living cells in survivors?
Gains fitness advantage, making it more likely it will survive and reproduce
All living cells will be descended from survivors, so they will all have ability to survive
What is the introduction of genetic material from one organism to another organism within the same generation?
Horizontal Gene Transfer
What are the 3 methods of Horizontal Gene Transfer? What does each one entail?
- Transformation - Direct pick-up of DNA from the environment
- Transduction - Transfer of DNA by a bacteriophage
- Conjugation - Transfer of DNA from one cell to another
Within transformation, where/what kind of DNA is picked up (list 3)?
- Plasmid DNA
- Chromosomal DNA
- Can be from any donor
Can all cells use Transformation as a method of Horizontal Gene Transfer?
No
What kind of cells can use Transformation? What do they need in order to BE a competent cell
Competent cells; Surface proteins that can recognize and take up DNA from the environment
Can you force cells to become competent? List an example
Yes; E.Coli DH5(alpha) in lab
How can we force cells to become competent?
Temperature and salt to change surface properties
Who was the first person to identify Transformation and what year did they identify it in?
Frederick Griffith 1928
Originally, Griffith was trying to develop a vaccine for what bacteria? How many strains was he working with?
- Streptococcus pneumonia
- 2
What are 2 characteristics of a S (smooth) Strain?
- Have capsule that allows them to escape host immune system
- Virulent
What are 2 characteristics of a R (rough) Strain?
- Does not have capsule, so cannot escape host immune system
- Avirulent
What were the 4 ways Griffith carried out his experiment and what were the results? What was the 5th step/reason for the 5th step?
- Live cells of S-strain was injected into mouse - Mouse dies
- Dead (heat-treated cells) of S-strain injected into mouse - Mouse lives
- Live cells of R-strain injected into mouse - Mouse lives
- Dead (heat-treated) S-strain cells and live R-strain cells injected into mouse - Mouse dies
- Streptococcus isolated and cells with capsules are identified
What does the Griffith Experiment show?
Live R-strain + Dead S-strain (both avirulent) ——> R-strain was transformed to S-strain (virulent)
What is a bacteriophage?
Bacteriophage
In transduction, DNA is transferred from one cell to another by?
Bacteriophage
Name the 4 stages of a Bacteriophage’s life cycle
- Attach to bacterial surface and inject viral DNA and enzymes
- Cut up host chromosome to disable it
- Host enzymes are used to replicate viral DNA and make more phage particles
- Host cell bursts and new bacteriophages released to environment
Describe the last step of the bacteriophage life cycle IN DETAIL
Packages genome into protein shell, which will be able to infect another cell
What is Transduction in bacteriophages?
Consequence of a mistake in last step of bacteriophage life cycle
What happens during Transduction in bacteriophages?
Newly-made bacteriophage accidentally packages host’s bacterial DNA instead of viral DNA, so when bacteriophage infects new cell - new cell receives bacterial DNA instead
What is conjugation?
Direct transfer of DNA from one living cell to another using a pilus
What is a ‘tunnel’ between two cells that connect their cytoplasms?
Pilus
To form a pilus, a special gene is needed. What is this gene called?
F-Factor
Where are 2 possible places an F-Factor can be found?
- Plasmid
- Bacterial chromosome of HFR cells
When an F-factor is found on a plasmid, what is it called?
F-plasmid
What does HFR in HFR cells stand for?
High Frequency of Recombination
How do rapidly-changing organisms have new clinical significance?
Bacteria can acquire new virulence factors
What makes Anthrax such a lethal disease?
Its toxin
Bacillus anthracis is similar to Bacillus cereus. What is the defining factor(s) in Bacillus anthracis that sets it apart from Bacillus cereus?
Contains plasmids encoding toxins and immune-system evasion methods
What toxin does Vibrio cholerae make?
Cholera Toxin
What is the primary cause for symptoms of Cholera?
Its toxin
What does Vibrio cholerae produce and what is it carried by?
Toxin carried by filamentous CTX phage (bacteriophage)
Some strains of E.Coli have acquired _________
toxin-producing genes
What other bacteria did E.Coli get its set of toxin-producing genes from? Which method did it use to acquire this set?
Shigella dysenteriae; Conjugation
What disease can the toxin from E.Coli lead to? What are the MAJOR symptoms that can be caused by this disease?
Hemolytic uremic syndrome; Kidney failure and death
Clavamox is a combination of what 2 drugs?
clavulanic acid and Amoxicillin
What 2 drugs are used alongside each other to treat Tuberculosis?
Rifamp and Isoniazid
