Lecture 9 & 10: Microbial Control & Antimicrobials Flashcards
What is the use of drugs to treat a disease?
Chemotherapy
What interfere with the growth of microbes within a host?
Antimicrobial drugs
What are substances produced by a microbe that, in small amounts, inhibits another microbe that are also antimicrobial drugs?
Antibiotics
What is a drug that kills harmful microbes without damaging the host?
Selective toxicity
What are produced by a microbe and further modified to enhance its function?
Semisynthetic antibiotics
What are produced by chemical synthesis to mimic the naturally occurring compounds?
Synthetic antibiotics
These are what:
-broad-spectrum
-superinfection
-narrow-spectrum
-bactericidal
-bacteriostatic
The actions of antimicrobial drugs
What are against many bacteria, overuse contribute to resistance?
Broad-spectrum
What is an infection occurring after or on top of an earlier infection, especially following treatment with broad-spectrum antibiotics?
Superinfection
What kills bacteria?
Bactericidal
What stops bacteria from reproducing, while not necessarily killing them otherwise?
Bacteriostatic
What kill or inhibit limited species of bacteria?
Narrow-spectrum
Many types of superinfection have been caused by the overuse of what?
Broad-spectrum antibiotics
Which type of antibiotic are more recommended because of its specificity that allows for your body to not be exposed to other types of microbes?
Narrow-spectrum antibiotics
Who won the 1908 Nobel Prize for the “magic bullet” - chemicals that could be designed to bind to and kill specific microbes or tumor cells
Arsenic compounds for syphilis patients: Trypan Red for sleeping sickness - killed trypanosomes and another that worked against treponemes
600 derivative compounds tried
Paul Ehrlich
Who won the Nobel Prize in 1945 for the 1928 discovery of penicillin, produced by Penicillium
Zone of inhibition: circular area around the spot of the antibiotic in which the bacteria colonies do not grow
Alexander Fleming
Who won the Novel Prize in 1939 for Sulfa Drugs – Sulfanilamide?
Red-dye Prontosil converts to sulfanilamide
First antimicrobial agent used to treat wide array of infections
Gerhard Domagk
These are:
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Disruption of cell membrane
- Inhibition of a metabolic pathway
- Inhibition of DNA or RNA synthesis
- Inhibition of pathogen attachment
Mechanisms of Antimicrobial action
What are the six mechanisms of antimicrobial action?
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Disruption of cell membrane
- Inhibition of a metabolic pathway
- Inhibition of DNA or RNA synthesis
- Inhibition of pathogen attachment
Describe penicillin mechanism
Penicillin interferes with the linking enzymes, and NAM subunits remain unattached to their neighbors. However, the cell continues to grow as it adds more NAG and NAM subunits. This makes the membrane wall very weak.
The cell bursts from osmotic pressure because the integrity of the peptidoglycan is not maintained
What can cause the inhibition of cell wall synthesis?
Most common agents act by preventing cross-linkage of NAM subunits
Most prominent in this group - beta-lactams
-function groups are beta-lactam rings
-Beta-lactams bind to enzymes that
cross-link NAM subunits
Bacteria have weakened cell walls and eventually lyse
Penicillin are effective against what type of organism?
Simplest beta-lactams: Aerobic Gram-positive organisms
Penicillinase enzyme breaks down into what?
Penicilloic acid
What are the reason bacteria become resistant to penicillin or can do so naturally?
They can produce the enzyme Penicillinase
What are the semisynthetic derivatives of beta-lactams?
More stable in acidic environments
More readily absorbed
Less susceptible to deactivation
More active against more types of bacteria
What are these:
More stable in acidic environments
More readily absorbed
Less susceptible to deactivation
More active against more types of bacteria
Semisynthetic derivatives of beta-lactams
Which generations of Cephalosporins are more effective against gram-negatives?
2nd, 3rd, and 4th generations
These are what:
-Vancomycin and cycloserine
-Bacitracin
-Isoniazid and ethambutol
Other inhibitors of cell wall synthesis
What interfere with bridges that link NAM subunits in many Gram-positives?
Vancomycin and cycloserine
What blocks secretion of NAG and NAM from cytoplasm?
Bacitracin
What disrupt formation of mycolic acid in mycobacterial species?
Isoniazid and ethambutol
What are the limitations of inhibition of cell wall synthesis?
Prevent bacteria from increasing amount of peptidoglycan
Have no effect on existing peptidoglycan layer
Effective only for growing cells
No effect on plant or animal cells; no peptidoglycan
Eukaryotic ribosomes are?
80S (40S and 60S)
Prokaryotic ribosomes are?
70S (30S and 50S)
What are these:
Prevent bacteria from increasing amount of peptidoglycan
Have no effect on existing peptidoglycan layer
Effective only for growing cells
No effect on plant or animal cells; no peptidoglycan
The limitations of inhibition of cell wall synthesis
What are the inhibitions of protein synthesis?
Drugs can selectively target translation
Prokaryotic ribosomes are 70S
Eukaryotic ribosomes are 80S
Mitochondria of animals and humans contain 70S ribosomes; can be harmful
What are these:
Drugs can selectively target translation
Prokaryotic ribosomes are 70S
Eukaryotic ribosomes are 80S
Mitochondria of animals and humans contain 70S ribosomes; can be harmful
Inhibitions of protein synthesis
What is an inhibitor of protein synthesis that is:
broad spectrum
binds to 50S subunit
inhibits peptide bond formation
Chloramphenicol
What is an inhibitor of protein synthesis that is
broad spectrum
Streptomycin, neomycin, gentamicin
Changes shape of 30S subunit
Aminoglycosides
What is an inhibitor of protein synthesis that is
broad spectrum
interferes with tRNA attachment
Tetracyclines
What is an inhibitor of protein synthesis that is
Gram-positives
Binds 50S, prevents translocation
Macrolides & Erythromycin
What causes the disruption of cytoplasmic membrane?
Some drugs become incorporated into cytoplasmic membrane and damage its integrity
Polymyxin
-disrupts cytoplasmic membranes of Gram-negative
-Toxic to human kidneys
Amphotericin B (polyene) attaches to ergosterol found in fungal membranes
-Humans somewhat susceptible because cholesterol similar to ergosterol
-Bacteria lacks sterols; not susceptible
Attaches to ergosterol found in fungal membranes
-Humans somewhat susceptible because cholesterol similar to ergosterol
-Bacteria lacks sterols; not susceptible
Amphotericin B (polyene) causes the disruption of cytoplasmic membrane
When differences exist between metabolic processes of pathogen and host, antimetabolic agents can be effective
causes inhibition of metabolic pathways
What
-disrupts cytoplasmic membranes of Gram-negative
-Toxic to human kidneys
Polymyxin
causes the disruption of cytoplasmic membrane
What is an antimetabolite is a chemical that inhibits the use of a metabolite?
Metabolic antagonists
What are the competitive inhibitors of metabolic pathways?
Sulfonamides (Sulfa drugs)
-inhibit folic acid synthesis
-broad spectrum
PABA is?
Para-aminobenzoic acid
PABA is?
a starting compound
normally bound to an enzyme with other substrates
Trimethoprim inhibits what?
inhibits at the second step of metabolic pathways
In Sulfonamides mechanism, how do they interact with PABA?
It competes with PABA for the active site and PABA will not be able to bind and create dihydrofolic acid and not make DNA and RNA
Sulfamethoxazole inhibits what?
Inhibits the first step of the metabolic pathway
What are the effects of Sulfonamides (Sulfa drugs) that inhibit folic acid synthesis on humans?
Since humans obtain folic acid from diet; metabolism is unaffected
What can antiviral agents do?
Target unique aspects of viral metabolism
How does inhibition of nucleic acid synthesis work?
Several drugs function by blocking DNA replication or mRNA transcription
Only slight differences between prokaryotic and eukaryotic DNA
Why are drugs that inhibit nucleic acid synthesis not normally used to treat infections?
Because drugs can affect both types of cells (eukaryotic and prokaryotic) which means human cells can be targeted and harmed
Used in research and perhaps to slow cancer cell replication
Why are inhibition of nucleic acid synthesis most often used against viruses?
Viral DNA polymerases more likely to incorporate
Viral nucleic acid synthesis more rapid than that in host cells
What are the effects on shapes of inhibition of nucleic acid synthesis?
Distort shapes of nucleic acid molecules and prevent further replication, transcription, or translation
Compounds can interfere with function of nucleic acids (nucleotide analogs)
Inhibition of nucleic acid synthesis
Effective against rapidly dividing cancer cells
Inhibition of nucleic acid synthesis
inhibitors of nucleic acicds
Prevention of virus attachment
Attachment can be blocked by
-peptide and sugar analogs of attachment or receptor proteins (attachment antagonists)
-still in developmental stage
Inhibition of pathogen attachment
Mechanisms of antimicrobial action
Readily available
Inexpensive
Chemically stable
Easily administered
Non-toxic and non-allergenic
Selectively toxic against wide range of pathogens
Characteristics of an ideal antimicrobial agent
Diffusion susceptibility test
its a picture
If infection is external what drug do you administer?
Topical
ointment, liquid solution that is applied on to the outside of the skin
What is the type of drug that is the simplest and has
- lower drug concentrations in blood
- no reliance on health care provider
- patients do not always follow prescribing information
Oral drugs
Oral drugs have these characteristics
- lower drug concentrations in blood because you lose some in digestive tract
- no reliance on health care provider
- patients do not always follow prescribing information
Drug that requires needle for administration
Intramuscular drug
Concentration never as high as IV administration
Drug that requires needle or catheter
Intravenous drug
Drug concentration diminishes fast as liver and kidneys remove drug from circulation
Do you need to know how antimicrobial agent will be distributed to infected tissues?
Yes, to know the cause of the problem and how the antimicrobial agent will be distributed in order for you to effectively get the drug to infected tissues
What are the three main categories of side effects?
Toxicity
Allergies
Disruption of normal microbiota
Drug resistant organisms in the population
Some organisms are naturally, partially, or completely resistant
Resistance by bacteria acquired in 2 ways
- new mutations of chromosomal genes
- acquisition of R-plasmids via transformation, transduction, and conjugation
- new mutations of chromosomal genes
- acquisition of R-plasmids via transformation, transduction, and conjugation
Resistance by bacteria acquired in 2 ways
Tolerance to a usually toxic substance as a result of exposure to a similarly acting substance
Cross resistance
Multiple resistance and cross resistance
Pathogen can require resistance to more than one drug at a time
Common when R-plasmids exchanged
Develop in hospitals and nursing homes; constant use of drugs eliminates sensitive cells
Superbugs
Cross resistance: tolerance to a usually toxic substance as a result of exposure to a similarly acting substance
What can be done for drug resistance?
High concentrations of drug
- maintained in patient for long enough time
Why do we use antimicrobial derivatives? What are the derivatives of Penicillin, cephalosporin, monobactam?
to expand the spectrum of activity, improve potency, reduce side effects, and overcome emerging resistance to existing antimicrobial agents. By modifying existing antimicrobials, new versions that are more effective against a wider range of microbes or have better therapeutic properties can be created
they are derived from the original penicillin-G structure, and the derivatives included are penicillin G (benzylpenicillin), penicillin V (phenoxymethylpenicillin), penicillin VK (phenoxymethylpenicillin potassium), and procaine penicillin.
What are the limitations of cell wall synthesis inhibitors?
Cell wall synthesis inhibitors, like penicillin and vancomycin, have limitations in microbiology mainly due to the emergence of bacterial resistance mechanisms, where bacteria develop ways to evade the antibiotic’s action by altering the target proteins or hindering drug entry, leading to reduced effectiveness against certain bacterial strains, like the Gram-negative bacteria due to their outer membrane barrier. Their activity can be affected by the growth phase of the bacteria, with slower-growing bacteria often exhibiting increased tolerance to these antibiotics.
Name examples of metabolic pathways inhibitors and their specific inhibitory actions. What is PABA and how is its activity blocked?
Trimethoprim and Sulfamides: often used together as antibiotics and inhibit the synthesis of folic acid, a crucial molecule for bacterial metabolism.
Fluoroquinolones: antibiotics inhibit DNA gyrase, an enzyme essential for bacterial DNA replication, disrupting their cell division.
Penicillin: antibiotic interferes with the synthesis of peptidoglycan, a key component of bacterial cell walls, ultimately leading to cell lysis.
Isoniazid: drug specifically targets the synthesis of mycolic acid, a lipid important for the cell wall of Mycobacterium tuberculosis, making it effective against tuberculosis
Name examples of nucleic acid synthesis inhibitors and their specific inhibitory actions
fluoroquinolones (ciprofloxacin), rifampicin, and nucleoside analogs (acyclovir), which inhibit bacterial DNA replication by targeting topoisomerases, RNA polymerase, and nucleotide incorporation respectively, thereby disrupting the process of nucleic acid synthesis within the microbial cell.
Describe the relative drug concentration in blood when administered by oral vs. intramuscular vs. intravenous routes
Oral: lower drug concentrations in blood
Intramuscular: concentration never as high as IV administration
Intravenous: highest drug concentration out of all 3; drug concentration diminishes fast as liver and kidneys remove drug from circulation
Describe the routes of drug administration
Topical: ointment, liquid solution that is applied on to the outside of the skin
Oral: lower drug concentrations in blood, taken by mouth
Intravenous: requires needle or catheter; drug concentration diminishes fast as liver and kidneys remove drug from circulation
Intramuscular: requires needle; concentration never as high as IV administration
