BACTERIA & ANTIMICROBIALS Flashcards
Differentiate between Exotoxins and Endotoxins
Exotoxins - Proteins secreted by living pathogen that destroy extracellular and cellular structures
Endotoxins - The release of harmful agents from within a cell, after the cell disintegrates.
What is a lipopolysaccharide (LPS) and what does it do?
A complex structure released by gram - or gram + bacteria; it triggers inflammation, blood coagulation, or acute whole body inflammation.
If an LPS is released from a gram - bacterium, what is the most common outcome?
Inflammation (Activation of macrophages, neutrophils, pyrogens)
What is the purpose of a ribosome? What is the difference between a prokaryotic ribosome compared to a Eukaryotic one?
Protein Synthesis
Prokaryotic Ribosomes are smaller and can be found inside eukaryotic mitochondria.
What is an Endospore?
Free spores that are released by Gram - bacteria. They vegetative cells, are resistant to environmental factors, and are formed in response to environmental signals
What are endospores composed of?
Vegetative cells in response to environmental signals
Is it more common for genetic mutations in bacteria to be expressed as a phenotype?
No, much more rare to be physically observed.
What makes bacterial cells more likely to mutate?
They are haploid, making the chances of mutation higher than diploid cells.
What is a horizontal gene transfer?
Transfer of genetic information from same-generation bacterial cells (i.e. Brothers).
What is a unidirectional transfer of genetic information?
Transfer of information from dead bacteria to living bacteria
Describe the 3 types of DNA exchange in Bacteria:
Transformation
Transduction
Bacterial Conjugation
- Transformation - exogenous DNA from dead bacteria picked up by living bacteria.
- Transduction - Transfer of information by Bacteriophage
- Bacterial Conjugation - Physical contact between cells mediated by pili
Explain the actions of a bacteriophage during the transduction exchange.
Bacteriophages contain viral DNA that is implanted in bacterial cells. From there the NEW information becomes part of the bacterial DNA and the replication of daughter bacteriophages begins (sometimes killing bacterial host).
https://www.youtube.com/watch?v=7stZk6TesKk
Explain the actions of bacterial conjugation in detail.
Conjugation is the transfer of genes from one cell to another via the Pili. The donor cell has what is called F+ factor (specific plasmid), whereas the recipient lacks F+ factor and is considered F-. F+ is extracted in Donor and transferred to F- recipient via the pili system. Once there, a complementary strand is synthesized in both the donor (who is missing half the plasmid), and the recipient (who has half the plasmid).
https://www.youtube.com/watch?v=EtxkcSGU698
Briefly Define the following means of controlling Microbes: Sterilization Ethylene Oxide Ultraviolet Light Gamma Radiation Disinfection
Sterilization: All cells killed (non-selective) i.e. Autoclave
Ethylene Oxide: Non-heat resistant bacteria
Ultraviolet light: Kills bacteria on surfaces; but not always effective (hiding)
Gamma Radiation: Used on food to rid of mold, used on surgical tools and medical equipment
Disinfection: Liquids that kill bacteria
Define antiseptics and how they affect bacteria
Chemicals that are used on skin or other tissues that reduce bacterial load (Iodine, 70% alcohol, isopropanol)
Define antibacterial agents (Antimicrobials) and how they work.
Medicines (natural or antibiotic) that reduce to bacterial load to a point that the immune system can take over and manage the infection (weakens bacteria)
What are antibiotics?
Natural agents that are secreted by one microorganism against another microorganism. They destroy structures present in bacteria, but not in the host.
What is the difference between bactericidal antibiotics and bacteriostatic antibiotics
Bactericidal - Irreversible drug that kills targeted microbes
Bacteriostatic - Reversible growth inhibition (prevent replication)
If a bacteria releases endotoxins upon cellular death that is harmful to the host, which type of antibiotic should be used and why?
Bacteriostatic antibiotic - it would stop the growth/spread of harmful bacteria, while the immune system can rid of bacteria with minimal death leading to endotoxic release
What is the major structural component of a bacterial cell that makes it susceptible to antimicrobials?
Peptidoglycan layer
How do beta-lactams work against bacteria?
Prevent the cross-linkage of NAM subunits in peptidoglycan by binding to the enzymes that cross-link them.
How do antimicrobials geared at inhibiting protein synthesis fight bacteria?
They target prokaryotic ribosomes and disrupt the creation of proteins which are vital for cellular life.
Explain how to inhibition of metabolic pathways is an effective antimicrobial.
Metabolism is the chemical reactions that take place within an organism; anything to disrupt the chemical reactions of a bacterial cell will lead to cellular death.
What is PABA, and how do sulfonamides interact with PABA to kill the bacterial host?
PABA is an acid that is crucial for the synthesis of nucleotides used in DNA & RNA.
Sulfonamides compete with PABA at the site of the enzyme “dihydrofolic acid”; thus decreasing production of DNA and RNA… leading to decreased metabolism and eventual death.
How do drugs kill bacteria by inhibiting nucleic acid synthesis?
By blocking either the replication or transcription phase of DNA or RNA, thus killing the cell.
*Not typically used in humans as it affects all cellular DNA & RNA
What is the “Spectrum of Action”?
The number of pathogens a specific antimicrobial agent can be effective against. Some drugs are considered Broad spectrum because they can be effective against a large amount of bacteria, visa versa.
What is a diffusion of susceptibility test? and what is the “Zone of inhibition”?
Susceptibility test is when a pathogen is spread across a petri dish, and a small amount of antimicrobial is attached to dish to assess effectiveness of drug.
Zone of inhibition is the area around the drug in the petri dish where no bacteria grow. (Larger the zone = more effective drug)
Explain the pros and cons of each method of antimicrobial administration.
Oral - Lower drug concentrations, patient administered (Poorer adherence to prescribed administration routine). Ø use of needles, less required from practitioner
IM - Slow diffusion into system, but lower drug concentration than IV therapy.
IV - Initial concentration is high; however, concentration can rapidly diminish as kidney and liver remove the drug unless continuously administered.
Give an example of how a drug resistant bacterium deactivates a drug?
Beta-lactamases (enzymes) that destroy the beta-lactam ring of penicillin, rending them useless
How might a bacterium slow or halt the entry of a drug into its cytoplasm?
Changes in structure of cell wall, electrical charge of cytoplasmic membrane
If a bacterium is sensitive to a specific antimicrobial that targets the bacteria’s metabolic process, how can the bacterium potentially resist this drug?
By altering the metabolic process targeted or abandon the metabolic process altogether.
What is an Efflux pump and what powers it? why do bacteria use them?
Used to pump antimicrobial out of the cell before the drug can act. Typically powered by ATP. Usually responds to more than one type of antimicrobial
What is cross resistance?
When a bacteria becomes resistant to a specific drug and drugs of similar structure.
What are the 4 ways antimicrobial resistance can be avoided?
- Higher concentration of the drug to remain in the body longer, inhibiting pathogen.
- The use of multiple antimicrobials concurrently to increase effectiveness and reduce resistance
- Limit use of antimicrobials to necessary cases
- Development of new antimicrobials, or alteration of existing drugs.
How does Penicillin fight bacteria?
Uses beta-lactam ring to stop peptide bridge formation in Peptidoglycan.
Binds to enzyme that cross-links NAM subunits, and effectively stops the cross-bridging of NAM and NAG
This type of antimicrobial is ineffective against dormant bacteria. Why?
Penicillin
Beta-lactam ring halts the cross-bridging of peptidoglycan NAM and NAG subunits by binding to NAM-binding enzyme.
IF CELL IS NOT GROWING; PEPTIDOGLYCAN LAYER IS NOT EITHER… rending drug ineffective as cross-bridges are already made.
This antimicrobial works in similar fashion to Penicillin, by binding to the D-alanine x2 at the end of the chain; effectively preventing a cross-bridge between NAG AND NAM.
Vancomycin
What occurs to the D-alanine amino acid used by Vancomycin; rending the drug ineffective?
D-alanine amino acid mutates into Lactic acid and no longer binds to Vancomycin
How does Aminoglycosides and Tetracyclines work in the treatment against bacteria?
binds to 30S ribosomal subunit, halting protein synthesis inside the Ribosome
Why is Tetracycline considered Bacteriostatic while Aminoglycosides are considered Bactericidal? Especially when they both bind to the 30S ribosomal subunit and block tMRNA protein synthesis sites?
Tetracycline binds reversibly (Temporary), whilst Aminoglycosides bind irreversibly (Permanently).
Tetracycline works to weaken the bacteria to be removed by the cell, whereas Aminoglycosides work to destroy the bacterial cell altogether
Which of the following drugs has the adverse effect of damaging host flora? A/ Gentamycin B/ Tetracycline C/ Streptomycin D/ Vancomycin
B/ Tetracycline
Affects normal flora and can increase the risk of secondary infections
How do RNA synthesis inhibitors work?
Binds to DNA-dependant RNA polymerase and STOPS THE INITIATION OF mRNA SYNTHESIS
This drug disrupts the outer membrane of Gram - cells after binding to their LPS A/ Sulfonamides B/ Trimethoprim C/ Polymyxin D/ Rifamycin
C/ Polymyxin
Little to no affect on GRAM + because cell membrane is not exposed and thick peptidogylcan layer.
What is combination therapy?
The use of two or more antimicrobials to effectively fight the bacterium or as a temporary treatment while diagnosis is being made
What is the Minimum inhibitory Concentration test (MIC)? How does it work?
MIC testing determines the smallest amount of antimicrobial needed to inhibit growth/reproduction of a pathogen. Standardized amount of pathogen is added to tubes of antimicrobial agents where they are then incubated. The cloudier the tube = the less effective the dose/antimicrobial.
What is the Minimum Bactericidal Concentration Test (MBC)?
MBC determines the minimum amount of antimicrobial required to effectively kill the bacteria. Any growth that appears in the test demonstrates a bacteriostatic concentration/drug
What is the Therapeutic Index? What does a high Therapeutic index (TI) mean?
A ratio that compares the amount of a antibiotic that the patient can tolerate to the drug’s effectiveness. The higher the TI, the safer the drug… more can be taken with less/Ø side effects.
What does Therapeutic Window (Therapeutic Range) mean?
TW means the range of drug concentrations that are effective against a microbe without being excessively toxic.
PABA is:
A/ A substrate used in the production of Lactic Acid
B/ A type of Beta-lactamase
C/ Molecularly similar to to cephalosporins
D/ Used to synthesize folic acid
D/ Folic acid synthesis
Drugs that act against protein synthesis include: A/ Penicillins B/ Polymyxin C/ Aminoglycosides D/ Trimethoprim
C/ Aminoglycosides
The key to successful chemotherapy is: A/ Selective toxicity B/ A diffusion test C/ MIC test D/ The spectrum of Action
A/ Selective toxicity
Which of the following statements is relevant in explaining why sulfonamides are effective?
A/ They attach to sterol lipids in the pathogen, disrupt membranes and lyse cells
B/ Prevent the incorporation of amino acids into polypeptide chains
C/ Humans and microbes use PABA differently in their metabolism
D/ They inhibit DNA replication in both pathogens and human cells
C/ PABA is different in humans and bacterium