Antibiotics/vaccines quiz 6

Question 1

live attenuated vaccines

Answer 1

Live-attenuated vaccinesare made with a pathogen that is alive, but weakened. The pathogen can still reproduce a little bit, but not cause disease (e.g. the MMR vaccine)

Question 2

killed vaccine

Answer 2

Aninactivated or killed vaccineis what it sounds like. The pathogen is completely dead, but the antigen still promotes an immune response. The Salk polio vaccine is an example.

Question 3

Toxoid vaccine

Answer 3

Toxoidvaccines are used for some bacterial vaccines. Instead of including antigens from the pathogen’s surface, an inactivated version of a toxin that the bacteria produces is used. The DTaP vaccine is a toxoid vaccine.

Question 4

subunit vaccines

Answer 4

If only part of the pathogen is used to make the vaccine, this is referred to as asubunit vaccine(the Pertussis portion of the DTaP vaccine is a subunit vaccine).

Question 5

rna vaccines

Answer 5

RNA vaccines such as the one used to prevent COVID-19 infection, use short RNA transcripts wrapped in simple lipids. The lipid vesicles enter human cells and deliver the RNA, which travel to the ribosome and produce viral proteins. The viral proteins displayed on the cell’s surface trigger an immune response and the production of Memory B and T cells specific to the viral protein.

Question 6

newer method virus like particles

Answer 6

virus-like particles are a technology where the capsid or envelope of the virus is made in a laboratory, but without any genetic material inside. This way, the antigens can be presented to the immune system intact without any risk of the virus causing infection. The HPV vaccine uses this method.

Question 7

newer method: maternally administered

Answer 7

Maternally-administered vaccines inoculate the mother, who then passes antibodies on to their infant through breast milk. A new vaccine for RSV that may be out next year uses this method.

Question 8

adjuvants/additives

Answer 8

Adjuvants arechemical additives to vaccines that are able to boost immune response through various mechanisms. These include possibly clumping vaccine particles at the injection site (which recruits more APCs) or directly stimulating immune cells.

Question 9

us liscensed adjuvants

Answer 9

In the United States, the only adjuvants that are licensed for use arealuminum-based compounds,which are included in the HepA and HepB vaccines, for example.

Question 10

thimerosol additive

Answer 10

Thimerosolis a preservative (not an adjuvant) containing trace amounts of mercury. It was used in some vaccines to prolong shelf life. It has been taken out of all vaccines given to children under 6, and is only now included in some multi-does flu vaccine vials. It is often discussed as one of the possible reasons for the (disproven) hypothesis that vaccines are associated with autism. Some anti-vaccine literature suggests it was used in the MMR shot, however, it never was. Thimerosol was removed as a precaution and because better preservatives were developed.

Question 11

Epitope prevention

Answer 11

Reverse vaccinologyis a method ofepitope prediction.Anepitopeis the specific chemical site on an antigen to which an antibody binds. It can be helpful to try to identify good epitopes for antibody binding in advance, instead of having to try many different antigens. For certain diseases that mutate very quickly, it can be hard to identify epitopes that are consistent between strains. For example, there are many strains of HIV; far more than could all be included in one vaccine. However, if there is an epitope found on the surface of most or all strains of HIV, it could be used as a target for vaccine development. In reverse vaccinology, researchers compare the genetic sequences of many different strains of the vaccine, looking for regions of the genome that are always consistent. These are areas that don’t mutate much, likely because the virus needs that very specific protein for survival. When they identify a region, it becomes a good antigen to potentially include in a vaccine.

Question 12

vaccine development

Answer 12

There are many ways in which vaccines are developed. The first stage typically involves testing within animals or human tissues in the lab. Scientists use different methods of inactivating the virus, and assess the safety of the resulting particles. Once the vaccine is shown to produce an appropriate immune response, it can progress to clinical trials.

Question 13

vaccine delivery

Answer 13

The most common method for delivering vaccines isintramuscular injection.However,oral vaccines(like the Sabin polio vaccine) andnasal spraysare also used to deliver certain live vaccines. The newest form of delivery is calledvaccine patches.They are still under development. The patches have microscopic needles on them coated in vaccine that penetrate just the very outermost layer of the skin when you put it on. You don’t feel the needles doing this. These patches hold a lot of promise for both preventing needle-sticks among health care workers and creating increased immunity. You have far more immune cells right under the surface of your skin (to respond to scratches and cuts) than you do deep in your muscles. So delivering vaccine directly under the skin can increase the number of immune cells exposed, and thus the immune response. However, tests so far have been inconsistent in demonstrating effective immune response. Methods for developing, coating, and administering the patches continue to be improved.

Question 14

antibiotic

Answer 14

Anantibioticis a naturally occurring compound that can kill a microbial organism (bacteria/parasite).

Question 15

antimicrobial compounds

Answer 15

Antimicrobialcompounds are a group of chemicals that includes antibiotics as well as synthetic compounds that can also kill bacteria. There are multiple mechanisms of action for antibiotics, including interfering with building of cell walls and synthesis of nucleic acids. When a bacterial infection is suspected but isn’t identified yet, a doctor can prescribe a general antibiotic until it is identified.

Question 16

empiric vs. definitive therapy

Answer 16

When a bacterial infection is suspected but isn’t identified yet, a doctor can prescribe a general antibiotic until it is identified. This is calledempiric therapy.Once the bacteria is identified by laboratory tests, they are supposed to describe an antibiotic that is specifically tailored to that pathogen, which is calleddefinitive therapy.Doctors don’t always transition from empiric to definitive therapy the way they should, which can be a driver of antibiotic resistance.

Question 17

history of antibiotics

Answer 17

Antibiotics were in use a long time before we knew what they were. Traces of tetracycline have been found in ancient relics. Paul Erlich came up with the concept of a drug that would work as a “magic bullet”, and first screened chemicals for syphilis treatment. In 1928, Alexander Fleming formally discovered penicillin, which is produced by the moldPenicillum notatum. It wasn’t until WWII that Florey and Chain (British researchers) were able to purify and disseminate penicillin widely.

Question 18

beta lactams

Answer 18

Beta lactamsare a type of antibiotic that include penicillin and cephalosporin. They have a double-ring structure, and work by interfering with a protein that constructs bacteria cell walls. They are effective against many types of bacteria, but not against certain atypical organisms such as MRSA.

Question 19

tracyclines

Answer 19

Antibiotics that interfere with ribosome function includetetracyclines. They are named for their 4 ring structure, and work by physically preventing binding tRNA to the ribosome

Question 20

anti metabollites

Answer 20

Anti-metabolitesfunction by mimicking a chemical that the bacteria needs to metabolize (break down or change) to survive. (We’ll talk about an example in class)

Question 21

pharmacodynamics

Answer 21

Pharmacodynamicsis how antibiotics interact with both the bacteria and the patient. Pharmacodynamics can impact a lot of how effective an antibiotic is going to be.

Question 22

bacteriostatic vs bacteriocidal

Answer 22

Some antibiotics may inhibit bacterial growth(bacteriostatic), while others kill the organism(bacteriocidal).For example, if the antibiotic interferes with DNA replication it is likely bacteriostatic. If it causes cell lysis, it is bacteriocidal. Usually both are effective, but some infections (like meningitis) require bacteriocidal antibiotics.

Question 23

Minimum Inhibitory Concentration

Answer 23

Whether or not a strain is susceptible to antibiotics is determined by theminimum inhibitory concentration (MIC),which is the minimum amount of antibiotic for inhibiting growth.

Question 24

Miniumum bacteriocidal concentration

Answer 24

The minimum amount of antibiotic needed to kill a bacteria (if it is bacteriocidal) is theMinimumBacteriocidalConcentration(MBC).

Question 25

pharmacokinetics

Answer 25

Pharmacokineticsis how the patient impacts the concentration of the antibiotic in the body. When an antibiotic is administered, it goes through three stages: absorption, distribution (concentrated differently throughout the body), and metabolism/excretion (most excreted in same form). How quickly the antibiotic goes through each stage depends on a variety of factors. For example, it matters whether an antibiotic is hydrophobic or hydrophilic, how large the antibiotic is, and how it is administered.

Question 26

pharmacokinetics and dynamcis interact

Answer 26

Concentrations of antibiotics should be considered in the light of pharmacokinetic factors. In order to maintain an MIC or MBC, they have to be taken on a schedule. Since the body is working to metabolize or eliminate antibiotics, the concentration drops below the MIC/MBC after a certain amount of time. This is a prime window for resistance to develop. If you take your antibiotics as scheduled, you should stay above the MIC/MBC.

Question 27

anitbiotic side effects

Answer 27

ntibiotics can alter microbiome composition and allow for opportunistic pathogens to infect. Patients can also have allergic reactions to antibiotics, or experience side effects due to cellular toxicity. This is true of many antibiotics used to treat TB. At very high doses, certain antibiotics can even cause seizures. Therefore, antibiotics should be very carefully prescribed.

Question 28

superbug

Answer 28

When there is high morbidity and mortality due to a bacteria that has become resistant, it is often referred to as asuperbug.

Question 29

antibiotic resisitance background

Answer 29

Resistance occurs when bacteria mutate, and acquire the ability to avoid being killed or inhibited by an antibiotic. Bacteria with a resistance gene will quickly reproduce and become a predominating strain within a patient. Each year, 2 million people in the US are infected with a resistant strain, and 23,000 die. Of these, 14,000 are from strains ofC. difficile.When there is high morbidity and mortality due to a bacteria that has become resistant, it is often referred to as asuperbug.Resistance to pharmacotherapy is not only an issue for bacteria, but it can arise in cancer cells, parasites, fungi and other infections. Bacteria with acquired resistance include:TB, S. aureus, Acinetobacter, E. coli,andV. cholera.
Each new antibiotic has resistance to it eventually acquired, making the search for new antibiotics a task that needs to continue in perpetuity. Genes for B-lactamase enzymes (confer resistance to the penicillin class of antibiotics) are widely distributed in bacteria throughout the world. Many strains are resistant to 7-8 antibiotics, and some can even use antibiotics as a source of energy.

Question 30

resistance

Answer 30

Bacteria have one circular, dsDNA (double-stranded DNA) chromosome. This chromosome contains most of the genes necessary for the bacteria’s survival and replication. However, they can have multiple small pieces of circular DNA called plasmids that are outside of the main chromosome. Some of these plasmids containresistance (r) genesthat result from random mutation of the bacterial genome. Most random mutations do not confer resistance, or are actually harmful to the bacteria. However, due to random chance, some provide a protective benefit.

Question 31

Plasmids can be transferred from one bacteria to another primarily via three different methods:

Answer 31

Conjugation(transfer through pilus connection)
Transduction(transfer through bacterial virus, called a phage)
Transformation(direct uptake of DNA from outside the cell)

Question 32

HCT and VGT

Answer 32

When a bacteria takes up DNA from another source, it is calledhorizontal (or lateral) gene transfer(HGT). If a gene is inherited directly from a “parent” bacteria during reproduction, it is calledvertical gene transfer (VGT).When there is HGTandrapid mutation working together, becomes very difficult to control.

Question 33

intrinsic resistance

Answer 33

In the case ofintrinsic resistance,no mutation is necessary to confer resistance. The bacteria simply overcomes the antibiotic by making more copies of the protein that the antibiotic targets.

Question 34

humans creating resistance

Answer 34

Less than ½ of the therapeutic antibiotics in existence are for human use. They are used and discarded for many other purposes. It is hard to get good numbers, but tons of chemical microbicides and antibiotics are dumped into the environment by pharmaceutical companies (primarily abroad) just because a batch was not up to standards. There is also a dramatic overuse of antibiotics in the U.S. and internationally. It is estimated that 40-50% of patients with respiratory tract infections get antibiotics, although the vast majority are caused by viruses. In agriculture, antibiotics are often used prophylactically because it was thought that they improve weight gain of animals (not to treat or prevent infection). Thankfully this has been changing in recent years, though some farmers still give antibiotics deceptively or illegally. When animals consume antibiotics, they not only can develop resistance in themselves, but their fecal matter can contain bacteria with resistance genes, that are then spread over wide acres of land as fertilizer. The bacteria in the manure then trade plasmids with others in the soil, spreading resistance genes incredibly fast.

Question 35

what can we do about antibiotic reisistacne

Answer 35

Plans to mitigate the problem of antibiotic resistance include both identifying resistant bacteria earlier, and developing new methods for identifying antibiotics or other antimicrobial therapies. For example, genotyping of strains in clinics to test for resistance is on its way to becoming common practice. Another common strategy is to use combinations of antibiotics, so that the bacteria is not able to acquire resistance. This is a method used often in the treatment of drug-resistant TB. Some researchers are trying to find ways to use bacteriophages (viruses that kill bacteria) to attack bacteria, which is a treatment approved in some other countries. Developing policies around antibiotic prescriptions, development of new antibiotics, use of antibiotics in agriculture and raising global awareness will also certainly be essential to mitigate and manage the problem of antibiotic resistance.