Microbiology 3050 Vaccines and Drugs

Antigen =

any molecule or substance that stimulates the immune system to make antibodies against it and activates immune memory

Vaccine =

the substance given to a host (usually by injection) that induces artificial active immunity, acts as an antigen but DOESN’T cause disease

Vaccination =

the inoculation of a host with a vaccine to stimulate protective active immunity

A ______ may be required to enhance or restore protection

booster, like a reminder to your immune system

Initial exposure to an antigen causes a …

primary immune response, this response takes some time and is not as robust as the second exposure, the second immune response to a second exposure happens faster and is larger because your body has memory of the antigen

There are three main approaches to making a vaccine:

Using a whole virus or bacterium, using the parts that trigger the immune response, or using just the genetic material

The whole microbe approach to making vaccines includes:

Inactivated vaccine - killing the microbe, Live-attenuated vaccine - weakening the microbe, or viral vector vaccine - placing the genetic material of the desired virus into a harmless virus

The subunit approach to making vaccines only uses …

very specific parts of a virus or bacterium that the immune system needs to recognize

The genetic approach (using just the genetic material) uses …

the genetic material for specific proteins, can be DNA or RNA, these vaccines are often called nucleic acid vaccines

SARS-CoV-2 is the virus that …

causes covid-19, called corona-virus because the bacteria has a crown structure

SARS-CoV-2 has spike proteins which act as the …

antigen

Several methods were used to make vaccines for covid-19, Pfizer and Moderna used …

an mRNA vaccine, inject mRNA that gives your cells instructions on how to make the spike protein, using just the spike proteins because the the entire genome must be present in order for the virus cause disease

The Johnson and Johnson method to make a covid vaccine was …

the viral vector vaccine method - placing genetic material for coding spike proteins into a harmless virus - like a trojan horse

You cannot contract the disease from …

getting a vaccine, you can have an immune response

Herd immunity =

resistance in a population to a pathogen as a result of the immunity of a large population, breaks the chain of pathogen transmission from one susceptible host to another

The more highly infectious a pathogen the …

greater the proportion of immune individuals needed to maintain herd immunity and precent disease spread

The Flu vaccine is an RNA virus that …

mutates constantly, this is why getting a flu vaccine yearly is standard

A large her immunity is needed for a disease such as …

measles, its highly contagious, herd immunity helps protect people who cannot get the vaccine (could be allergic)

A population that is unvaccinated and not contracting the disease is called a …

naive population

Antimicrobial drugs are compounds used to …

treat disease by destroying or inhibiting the growth of pathogenic microbes within a host (in vivo)

There are three types of antimicrobial drugs:

synthetics, antibiotics, and semi-synthetics (antibiotics are just a category of antimicrobial drugs)

Synthetics are completely …

manufactured, there is no natural element to them, we are moving more towards synthetics because antibiotics have been in use for so long that bacteria are becoming largely resistant to them

Antibiotics are naturally …

produced antimicrobial agents - so they are microbial products produced by other bacteria and fungi

Semi-synthetics are …

chemically modified antibiotics

Antimicrobial drugs can be classified by their …

molecular structure, mechanism of action (what they target to kill/inhibit a cell), and by their spectrum of antimicrobial activity

General characteristics of antimicrobial drugs includes …

narrow or broad spectrum, whether they are cidal or static agents, and their side effects

Narrow spectrum drugs …

attack only a few different pathogens (some may attack only gram-negative cells)

Broad spectrum drugs …

attack many different pathogens

Side effects are …

undesirable effects of drugs on host cells (you)

What are the synthetic antimicrobial drugs that we need to know?

1 growth factor analog - isoniazid and a quinolones - ciprofloxacin

Growth factor analogs have a similar …

structure to an essential growth factor, they disrupt cell metabolism

What is the growth factor analog we need to know?

Isoniazid - its cidal if actively growing bacteria are present, otherwise, its static if the cells are dormant, it interrupts the production of mycolic acids, so its only effective against mycolic cells, making it a narrow spectrum drug

What quinolones drug do we need to know?

ciprofloxacin - is a broad spectrum drug and cidal under all conditions, commonly used to treat UTI’s

Quinolones interfere with …

bacterial DNA gyrase - prevents DNA packaging

Growth factor analogs have similar …

structure to essential growth factors, they disrupt cell metabolism

Antibiotics from bacteria that we need to know include:

tetracyclines, lipid biosynthesis disruptors, macrolides, all of the drugs associated with these that we discussed are static

Macrolides target …

the 50S (large) ribosomal subunit

Example of macrolides that we need to know =

erythromycin - is a broad spectrum drug, static, azithromycin (Z-pack) is a semi-synthetic macrolide that is widely prescribed)

Example of tetracyclines that we need to know =

tetracycline - broad spectrum and static, prescribed as an anti-acne medication

Example of lipid biosynthesis disruptor that we need to know =

platensimycin - broad spectrum, static, and effective against MRSA and VRE which are two drug resistant bacteria

Tetracyclines target …

the 30S (small) ribosomal subunit

Lipid biosynthesis disruptors target …

fatty acid biosynthesis

What is the last antimicrobial we discussed that includes penicillin and cephalosporins?

Beta-Lactam from fungi, targets cell wall synthesis, its effective primarily against gram-positive bacteria, cidal against actively growing cells

Penicillin G =

natural penicillin and its sensitive to acid, meaning if you were to take it orally your stomach acid would degrade it

By tinkering with antibiotics we can …

make them more effective or less affective, maybe both depending on the antiobiotic

Antimicrobial drug resistance =

the acquired ability of a microorganism to resist the effects of a chemotherapeutic agent to which it is normally sensitive - the superbug

Once resistance originates in a bacterial population it can be …

transmitted to other bacteria, resistance mechanisms are not confined to a single class of drugs

Erroneous practices select for …

the growth of resistant bacteria

Treating singly with an antibiotic is …

selecting for bacteria that are resistant to the antibiotic

We have problems in hospitals where a patient will come for something, and then while they are there …

their bacterial infection may be exposed to other bacteria that are floating around the hospital, then these bacteria they pick up have resistance, and horizontal gene transfer takes place, so the hospital is spreading resistance to patients, this is seen in Enterococci

HAI =

Hospital acquired infection - a man with a diabetic ulcer went to a hospital for an infection and while by MERSA, while there he was exposed to VRE and the MERSA horizontally inherited VRE’s resistance

Mechanisms of bacterial resistance:

target modification, preventing entrance, inactivation, efflux pumps, alternative pathways, and impermeability

Target modification =

when the target of an antibiotic mutates from horizontal gene transfer or spontaneous mutation, and now the antibiotic if ineffective

Preventing entrance =

when a bacterial cell produces an enzyme that leaves the cell and finds antibiotics near by and destroys or inhibits it before it ever enters the cell

Inactivation =

when the cell produces something that overwhelms the antibiotic making it useless (inactive)

Efflux pump =

a pump that exports antibiotics - can be effective against different kinds of drugs

Alternate pathway =

when some bacteria are afflicted by an antibiotic that targets metabolism, but the cell can use a different pathway to produce products

Impermeability =

when the cell has an attribute that prevents antibiotics from entering like a slime layer or a capsule

Only 1 in a million mutations …

result in resistance, this seems like very little, but we work with more than a million cells in lab, and there are more than a million in your body

Origin drug resistance is when …

the cell has natural immunity genes or immunity genes arise from spontaneous mutations, these genes can be located on chromosomes, plasmids, or mobile genetic elements such as transposons

Transmission drug resistance is when …

the cell obtains resistance through horizontal gene transfer such as transformation, conjugation, or transduction

Cells have to be ______ in order to take in DNA

competent

Antibiotic selective transfers can come from …

inappropriate prescribing practices, unregulated sell of antibiotics, failure to complete courses of antibiotics, use of suboptimal dosages, and use of antibiotics as animal growth enhancers

Not receiving a correct dosage or not completing a course of antibiotics can …

provide selection while not giving your body the upper hand in fighting infection, allowing resistant cells to live

Drugs should be given in high …

concentrations to destroy susceptible cells

Antimicrobials should only be used …

when necessary, and you should complete the full course

Use ______ spectrum antimicrobials to ensure that we aren’t …

narrow, applying unnecessary pressure to all bacteria which could include good bacteria that your body needs

Giving a combination of …

unrelated drugs can help prevent the emergence of drug resistance

Possible future solutions to emergence of drug resistance include:

development of new antibiotics and the use of bacteriophages - still in trial phases in U.S.