Pathophysiology, drug targets and resistance in viruses, (myco)bacteria & fungi Flashcards
Are targets dictated by pathogens or hosts?
pathogens
Advantage to have greater evolutionary distance between humans and pathogens
This would allow for them have more different targets which makes it easier to find specific drugs
Disadvantage to have closer evolutionary distance between human and pathogen?
tougher to find specific drugs
More essential pathogen targets (bigger genomes) means?
more drugs
Resistance mechanisms are dictated by?
pathogen or virus
Simple genomes of virus have how many genes?
5-50 genes
How do viruses acquire resistance?
through mutations in target genes occurring during lower fidelity gene replication
What is a resistant mechanism that bacteria and fungi have that viruses do not have?
Viruses do not have efflux pumps because they do not have a specific location for replication so there is no where for the efflux pump to be
Where do viruses replicate?
host cell
What does having complex genomes of thousands of genes mean for resistance mechanisms in bacteria and fungi?
lots of potential resistance mechanisms
What are three ways bacteria and fungi can acquire resistance through?
- modification of target genes and control elements and amplification of target genes
- activation of efflux pumps, lowered uptake, lowered activation of prodrugs
- activation of antibiotic metabolism/inactivation
Where does modification of target genes and control elements and amplification of target genes occur?
- pathogen chromosome or moveable elements like plasmids
2. Although mutations are genetic, most modified antibiotic-target interactions take place in the proteins these encode
What type of control occurs in activation of efflux pumps, lowered uptake, lowered activation of prodrugs?
genetic or non-genetic control
What type of control occurs in activation of antibiotic metabolism/inactivation?
genetic or non-genetic control
What is an advantage of viral targets?
humans can give selectivity
What is a disadvantage of viral targets?
small genomes mean few targets
What is true about viruses?
a. are always so small they can be seen with light microscope
b. are always obligate parasites of bacteria, archaea, or eukaryotes
c. never have genomes that code for enzymes important in their replication
d. all of the above are true
e. none of the above are true
b. are always obligate parasites of bacteria, archaea, or eukaryotes
What are two ways we treat viruses without antivirals?
- supportive therapy
2. vaccination
What is supportive therapy?
rest, fluids, OTC painkilers
When is supportive therapy appropriate?
only for mild, resolvable illness
What are 4 disadvantages of vaccinations?
- doesn’t always work
- constant mutations in viral genome can lead to different antigens
- for influenza, means you need a vaccine every year
- for HIV, no vaccine yet developed and approved
How do we treat viruses?
antiviral drugs
What are 2 main kinds of antiviral drugs?
- host directed immune therapies, e.g. interferons used in past for HepC
- Antiviral drugs