microbe nutrition + growth - post midterm Flashcards
chemotherapeutic agents
chemicals taken internally to kill or inhibit growth of microbes within host cell
= antibiotics: kill bacteria
= antifungals:
=antivirals
what is selective toxicity
allows chemicals to target the microbe without harming the host
most chemotherapeutic agents?
antibiotics - chemicals synthesized by microbes that are effective in controlling the growth of bacteria
Paul Ehrlich: discovered?
salvarsan
- organo-arsenic compound.
- treat syphilis, replaces mercury which was equally toxic
gerhard Damagk discovered?
dyes against streptococcus
- prontosil was first of sulfa drugs
alexander fleming discovereD?
penicillin
selman waksman discovered?
streptomycin
antibiotic use - human vs agriculture
huma = 36% agriculture = 64%
frequency of antibiotic type use
penicillin = 40% cephalosporin = 24% macrolides = 12% quinolones = 11%
what are dilution susceptibility tests
Minimum inhibitory concentration (MIC): lowest dose that prevents growth
Minimum lethal dose (MLD): lowest dose that kills pathogen. add antibiotic after growth
target in bacterial cells?
cell wall, dna synthesis.
attack things diff from human
what are sulfa drugs?
used as antibacterial.
more toxic to bacteria than host.
- sulfanilamide competitive inhibitor to PABA, PABA is substrate for folic acid synthesis. bacteria use folic acid to make nucleic acids - sulfa drug doesnt allow this
- bio-mimic molecule. bind to same binding site as molecule it binds
growth factor analogs
toxic to fast growing cells
- microbes, cancer cells
= halogenate = toxic
competitive inhibition
folic acid biosynthesis is reduced in presence of sulfa drug inhibitor. need more concentration of PABA to out-compete sulfa
what are quinolones
synthetic antibacterial compounds
- inhibit bacterial DNA gyrase, enzyme that supercoils DNA for packing into cell
- gram (-) effective
- B.anthracis effective
RNA synthesis inhibitors
rifamycin + rifampin
- bind RNA polymerase + block transcription
- not as selective bc prok and euk = not used as chemo agent
cell wall biosynthesis inhibitors
b-lactams
cyclic peptides.
penicillin (5), cephalosporin (6)
bind to transpeptidases: enyme cross-link peptidoglycan monomers, cause weakening of cell wall
some bacteria have b-lactamases break b-lactam rings - leads to antibiotic resistance
b-lactamases and cell wall
gram(-) : outer membrane impermebable to penicillin. b-lactamases in peiplasmic space
g+ more sensitive because no peri-plasmic space.
PG cross-linking in G-
no interbridge link. d-ala to DAP
PG cross linking in G+
peptide interbridge (5-glycine_ because d-ala to l-lys. not facing same direction
peptide bond formation as target for penicillin
transpeptidation by transpeptidase. transpeptidaes is penicillin binding protein = activtiy is blocked. Penicillin-PBP complex = autolysin release to prevent formation of peptide bond.
new penicillins on g-
b-lactam dont work bc b-lactamases.
now, penicillin structures not hydrolyzed by b-lactamases.
co-treatment of b-lactam drugs on g-
ampicillin + clavulanic acid
- b-lactamase binds to vlaculanic acid + ampicillin attacks b-lactamase
cycloserine
bacitracin
vancomycin
cell wall biosynthesis inhibitors
c: blocks d-ala peptidization
B: block dephosphorylation of bactoprenol phosphate (carries Nag/NAM across to PG)
v: block transpeptidation by binding d-ala
protein synthesis inhibitors
-aminoglycosides
macrolides
tetracyclines
A: inhibit protein synthesis by small subunit. hit g-
M: bind to large subunit of ribosome
T: broad-spectrum antibiotic
- inhibit tRNA attachement. g+ and g-
daptomycin
cyclic lipopeptide
- insert into cytoplasmic membrane, makes pore
- target g+ (bc no outer membrane, g- outer membrane protects leakage)
resistance from changes in cell membrane structure
anti-fungal difficult why
biological similarity between host + pathogen
- limits point of attak
what is targeted in anti-fungals?
sterols + chitin.
anti-fungal name?
nyastatin
what are superficial mycoses
fungal infection on outer surface of tissue.
- topical application of nystatin - don’t ingest can be toxic
antiviral drugs
developing
- disrupt RNA or DNA synthesis of viral pathogen.
interfere with replication of viral genome
- selectively problematic
- protease inhibitors against virus-specific enzymes
interferons: stimulate production of host anti-viral proteins
trick with antiviral why?
diff than bacteria or euk bc not it’s own cell. have to target virus without killing host even tho host cell is used
antibiotic resistance
- continues to build
- origin and transmission of antibiotic resistance involves chromosomal or plasmid genes for drug resistance
- plasmid transfer
what are nocosomial infections?
hospital-acquired.
4 mechanisms of resistance?
1.exclusion (efflux)
2enzymatic inactivation
3modification of antibiotic or target
4alternative pathway or increase target
sources of resistance genes
- bacterial chromosomes - spontaneous mutation
- plasmids: transferred with HGT
- mobile genetic elements
mechanisms of transfer
transformation: lost + picked up
conudation: transfer from M->F
transduction: viral delivery
preventing drug resistance
high concentrations
- 2+ drugs
- only when necessary
- develop new drugs + use bacteriophages (hard and inefficient, but less resistance)
