topic 11 Flashcards
What are some reasons why bacteria are resistant to antibiotics? What are some examples? What are some solutions?
Acquire genes that confer resistance (main way):
Beta lactam (augmentin) chloramphenicol acetyl transferase (chemical modification)
Develop resistance on their own by mutation:
Rifampcin (triple drug therapy for tuberculosis)
quinolones (results in a reservoir of resistant genes that other microbes can accquire)
Some bugs are naturally resistant:
aminoglycosides and anaerobic bacteria (combine with penicillins-synergism)
cephalosporins (multiple generations)
Pharmacokinetic factors:
Tissue penetration (boil, abscesses), MIC
What are plasmids? What are some characteristics?
They are small, circular, and episomal (exists outside of chromosome).
They are split into functional groups (replication group, mobilization group, conjugation group, passenger genes) that can put in and taken out (not dependent on e/o).\
There are multiple copies per cell
How do bacteria acquire resistance? How does it work? Is it species specific?
Via plasmids, specifically the conjugation group of a plasmid.
The male (with the plasmid) sends out a sex pili which is recognized by the female bacteria. It then reels her in, pokes a whole in her, and sends some cytoplasm containing the plasmid (including resistance genes if they’re there) through. It is a replicative process meaning that the original plasmid is replicated and the copy is sent through. This means that once it ends, both cells can then give the plasmid to a new female cell.
Plasmids can be shared between species (though certain species might be able to give it to certain other species, that species can give it to another, so they are all interconnected somehow) and can even conjugate with some eukaryotes.
How do resistant genes get onto plasmids?
Via Transposons
Transposons are jumping genes. They go from one place to another on a chromosome using insertion sequences (IS). sometimes, two transposons will end up near each other and then become one and with two insertion sequences, they can become a plasmid. Sometimes, a resistant gene ends up between the two transposons and enters into the plasmid.
What is transduction?
A bacteriophage (virus) binds to a bacteria cell, inserts its DNA/RNA, and the DNA/RNA is used to replicate their DNA/RNA and form proteins for more bacteriophages, then once all is formed, they lyse the cell. Sometimes, some bacterial DNA accidentally enters into the bacteriophage with its DNA and that bacteriophage can then transfer the DNA to another bacterial cell.
Basically, the bacteria uses the virus as a vector for their DNA.
Probably not as important as conjugation.
What is transformation?
Basically a bacteria sucks up DNA in their environment. Probably not as important as conjugation.
What are some clinical implications of the fact that resistance is acquired (transferred from one species to another)
Since acquisition is a rare event, if a patient’s infection responds to antimicrobial therapy, then resistance won’t happen in that patient on your watch (if the microbe in the patient isn’t resistant, it won’t all of a sudden become resistant; it has to be acquired).
A longer duration of therapy won’t in and of itself lead to resistance.
Phrophylactic administration of antibiotics won’t promote the occurence of an antibiotic restistant infection.
Patients who initially respond to antimicrobials and then get worse likely got a new bug (nosocomial)
Where did resistance genes come from?
They’ve always been around for the most part (penicillin is naturally occurring). Originally, they mutated from initially sensitive antimicrobial targets.
They get recruited by mobile genetic elements and engage in horizontal gene flow.
Resistant bacteria thrive under selection. Anti-biotic era provided great selection in places like (hospitals, farms, and the community. If in one person, a strain is resistant to an antibiotic, it grows and is then spread to other people and is able to persist better in other people b/c it is resistant to the antibiotic. It is not as if resistance is gained in each new person.
Most people get resistant microbes from their immediate environment (nosocomial, day care center, normal flora, etc.)
People travel all over the world which brings resistance genes all over the world.
What is piggy back selection?
Multiple resistance genes end up on one plasmid. Therefore, resistance to multiple drugs can be acquired in one fell swoop. Therefore, by giving someone penicillin, you might end up with bacteria that are selected for not just penicillin resistance but resistance to other microbes as well.
What can be done to cope with antibiotic resistance?
Develop new antibiotics
Do your part to reduce selective pressure (only use antibiotics when needed…explain to parents that the number one factor for having an antibiotic not work is previous exposure to an antibiotic).
Data accumulation shows that reduced use of antibiotics in a population lowers the antibiotic bacteria in the community (if there’s no selective pressure to be resistant, the bacteria will be at a replicative disadvantage if it has that plasmid).
Don’t use antibiotics as a feed additive on farms
