Final Material (10.13 - 12.6) Flashcards
(145 cards)
1
Q
what are microbial and fossil mats?
A
they are huge layers of microbes and fossils found in Antarctica and Australia, sometimes it is hard to tell if these are actual biological remnants or if they are simply plants or weird rock formations
2
Q
what are the various geological types of evidence of life?
A
- stromatolites
- microfossils
- isotope ratios
- biosignatures
- oxidation states
3
Q
what are stromatolites?
A
layers of phototrophic microbial communities grew and died, and their form was filled in by calcium carbonate or silica, ie ancient bacteria got filled in by CaCO4
4
Q
what are stromatolites?
A
- a type of geological evidence of life
- layers of phototrophic microbial communities grew and died, and their form was filled in by calcium carbonate or silica, ie ancient bacteria got filled in by CaCO4
5
Q
stromatolites
what are the advantages? what are the disadvantages?
A
advantages - fossil stromatolites appear in the oldest rock of the Archean eon, their distinctive shapes resemble those of modern living stromatolites
disadvantages - some layered formations attributed to stromatolites have been shown to be formed by abiotic processes
6
Q
what are microfossils?
A
- a type of geological evidence of life
- early microbial cells decayed and their form was filled with CaCO4 or silica, the size and shape of microfossils resemble those of modern fossils, these are quite subjective and thus the least reliable
- may use this to ID a good place to start looking and then do more exploration for confirmation based on other types of evidence
7
Q
microfossils
what are the advantages? what are the disadvantages?
A
advantages - microfossils are visible and measurable under a microscope, offering direct evidence of cellular form
disadvantages - microscopic rock formations require subjective interpretation, some formations may result from abiotic processes, most prone to mistakes
8
Q
what are isotope ratios?
A
- a type of geological evidence of life
- microbes fix 12CO2 more readily than 13CO2, thus limestone depleted of 13C must have come from living cells, similarly sulfate respiring bacteria cause depletion of 34S compared with 32S
- more 12C in the rock indicates bacterial life, rubisco of calvin cycle uses 12C
- rubisco uses 12C -> microbial cells converted into CaCO4 in sedimentary rock -> this rock will have mainly 12C NOT 13C
9
Q
isotope ratios
what are the advantages? what are the disadvantages?
A
advantages - highly reproducible physical measurement, they are generated by key biological reactions which can calibrate the time lines of phylogenetic trees, this is more measurable and less subjective
disadvantages - cannot prove absolutely that no abiotic process could generate a given isotope ratio, these ratios tell us nothing about the shape of early cells or how they evolved
10
Q
what are biosignatures?
A
- a type of geological evidence of life
- certain organic molecules found in sedimentary rock are known to be formed only by certain microbes, these molecules are biosignatures
11
Q
biosignatures
what are the advantages? what are the disadvantages?
A
advantages - biosigs such as hopanoids are complex molecules t specific to bacteria
disadvantages - a biosig though to be specific to one kind of organism may be discovered in others, in the oldest rocks organic biosigs are eliminated by metamorphic processes
12
Q
what are oxidation states?
A
- a type of geological evidence of life
- the ox state of metals such as Fe and uranium indicate the level of O2 available when the rock formed, banded iron formations suggest intermittent oxidation by microbial phototrophs
- typically we fine Fe2+ in crust rock and Fe3+ in rock indicates oxidation by present bacteria
13
Q
oxidation state
what are some advantages? what are some disadvantages?
A
advantages - oxidized metals offer evidence of microbial processes even in highly deformed rocks
disadvantages - it is hard to rule out abiotic causes of oxidation, even if oxidation was biogenic, it does not reveal what kind of metabolism took place
14
Q
why is it ideal to have more than one type of evidence present at a given site suspected to contain ancient microbial life?
A
there should always be at least two if not more types of evidence present when determining if a site as geological evidence for life, this is because all types of evidence have flaws and drawbacks, there are many different things which could lead to abiotic factors coming into play so the more evidence we have the more sure we can be that there was actually life in that site
15
Q
what are diatoms?
A
some kind of beautiful algae things
16
Q
compare and contrast historical and modern microbes?
A
these guys tend to have some fair similarity, today modern microbes may be a little more structured and adapted for our atmospheric conditions
17
Q
what is the proposed timeline for the origin and evolution of life on earth?
A
the planet earth formed during the Hadean eon (about 4.5 Gyr ago). the environment was largely reducing until cyanobacteria pumped O2 into the atmosphere. when O2 levels reached sufficient levels (about 0.6Gyr ago) multicellular animals and plants evolved, we had many photoautotrophs for a while before sufficient O2 and then things diversified
18
Q
what do we know about early metabolism?
A
- bacteria striated bases off of what photosystems they had
- they took advantage of atoms that were common before oxygen
19
Q
how do we measure evolutionary time using specific genes?
A
we can measure evolution of genes and species by examining the mutations in sequences over acquired over time, today we may sequence parts of genes or entire genomes to examine mutations, we look at what bases change and where in the sequence they are
- we start w a root sequence and develop tips based on the smallest number of mutations
20
Q
what gene do we typically use to distinguish bacteria and examine evolution over time?
A
SSU (small subunit of the ribosome) = rrn gene
16S in bact, 16SA in archaea, 18S in euks
this gene is highly conserved so small mutations can tell us a lot and be very distinguishable
21
Q
what is the molecular clock?
A
as genetic molecules reproduce, the number of mutations accumulated at random is proportional to the number of generations and thus the time since divergence
22
Q
how has NGS changed how we identify and examine bacteria?
A
it allows for much more rapid sequencing and many more sequences can be looked at at the same time
23
Q
how can we define relationships between bacteria based on changes to the DNA?
A
identity -> exact base pair matches
homology -> similar amino acids
- we can create DNA sequence alignments which allow for various organisms to be classified in relation to each other
- so get the sequences, align them, develop a phylogenetic tree
24
Q
how do we ensure we have generated a good phylogenetic tree?
A
one MUST have statistical analysis performed on their phylogenetic trees, the most common method for this is bootstrapping
25
talk about Carl Woese and his discoveries and life's work
carl woese is a classic old white guy who spent his entire career sequencing things (the old fashioned way with mile long gels), he discovered the archaea as their own kingdom but never got a nobel, one of his besties had a bunch of archaea so he took them and sequenced them, literally sequenced anything and everything under the sun that had a ribosome
26
talk a little bit about comparing the 3 domains of life
- the 3 domains of life are interconnected, there are some traits that Arc and Euks share, some that Arcs and Bacts share, and some that Euks and Bacts share while excluding the 3rd group respectively in all these scenarios
27
similarities between Bacteria and Archaea
cell volume, circular chromosomes, has just nucleoid (no membrane bound nucleus), multigene operons, vast options for metabolism, not multicellular
28
similarities between Eukaryotes and Bacteria
introns are common, they share homologs of their RNA polymerases and transcription factors, their ribosomes are resistant to some common antibiotics, Met as translation initiator (bact use f-Met, mitochondria also use f-Met)
29
what are the 3 domains of life?
Eukaryotes, Bacteria, Archaea
30
what are traits of all living organisms?
chromosome are double stranded DNA molecules, they all have a common ancestral RNA polymerase, there is a universal genetic code; common ancestral rRNA and elongation factors, some proteins have high conserved ancestral functional domains, their cell structures are all made up of an aqueous cell compartment enclosed by a membrane
31
how does horizontal gene transfer make a mess of phylogenetic trees?
- instead of normal accumulations of mutations over time, a species may just suddenly have a whole new operon
- able to observe HGT in real time with s. pneumoniae as it develops mutations really fast and in a matter of 7 months had changed over 7% of its genome in response to antibiotics
- how we obtained chloroplasts and mitochondria
32
what is the long term evolution experiment (LTEE)?
- a long term experiment to study the evolution of e. coli
- they have 12 cultures and everyday they inoculate fresh media with cells from the pervious culture, they take samples to freeze down and sequence
33
when did the LTEE begin?
1988
34
what are some new traits developed by the bacteria in the LTEE?
after like 33k generations they were growing better when in the presence of low glucose and higher citrate
35
how does a bacteria gain some adaptation?
- potentiation: random, maybe not really required mutation right off the bat, preparatory
- actualization: slightly better growth, maybe gaining more of an ability to use a certain material
- refinement: better system that actually utilize something not previously utilized
- we never really have BRAND NEW things pop up but rather do some heavy modifications
36
how does one, in general, tell 2 species apart?
there are generic ways such as physical properties and staining if DNA sequencing is not accessible or practical
37
what does is endosymbiosis refer to?
this refers to us acquiring chloroplasts and mitochondria as ancient bacteria that kinda made their home in eukaryotic cells, endosymbiotic cells evolved into our mitochondria and chloroplasts as they took up residence in euk cells
38
how did we determine the sequences of mitochondrial and chloroplast genomes? what are some genes they have?
sequencing lol
- these guys may use bact genes for some processes and nuclear genes for others
- since they were technically intracellular parasites they quickly lost certain functions
- they both have genes for making ribosomes and various tRNAs
39
deep branching thermophiles
- lots of HGT from archaea
- high mutation rates
- live in extreme environments = all extremeophiles
- they have a mixed/diverse metabolism
- limited number of examples bc hard to grow in lab
Ex - Dieococcus radiodurans (extremely UV resistant, 4-10 genome copies per cell, highly efficient and redundant DNA repair, membrane structure gram- but stain gram+, obligate aerobic chemoorganotrophs)
40
deep branching Gram negative (-)
- no common metabolism and morphology amongst them
- distinct from other Gram negs (proteobact)
- many are obligate anaerobes (fermentors)
- oxygenic photoautotrophs with thylakoid membranes
Ex - Fusobacteria (gram neg anaerobe found in septicemia and skin ulcers, forms biofilms, in dental plaque, normal in oral cavity, can cause septic shock)
41
cyanobacteria
- all phototrophs with PSI and PSII
- more membrane surface so more photosystems
Ex - Chroococcales (square colonies based on two division planes)
42
gram positive (+) bacteria
- 1 membrane and 1 thick cell wall
- stain purple
- mixed metabolism but NO photosynthesis and lots of fermentors
- all divided into Firmicutes (LOW G/C) (spore forming or non-spore forming) and Actinomyces (HIGH G/C)
Ex - Bacillus subtilis (many soil bacteria) and C. diff (GI nosocomial infection)
43
proteobacteria - normal gram negative (-) bact
- 2 cell membranes and 1 thin cell wall
- all stain pink
- we know the most about them bc they grow in our intestines
- contain alpha, beta, delta, gamma, epsilon
Ex - e. coli, enough said
44
spirochetes
- all the same characteristic shape
- have endoflagella, encased by sheath
45
catch all class
- chlamydiae, plantomycetes, verrucomicrobia
- unique growth and weird organelles
- tend to be euk like, somewhat
46
how many current major phyla of bacteria are there?
7
deep branching thermophiles, deep branching gram neg, cyanobacteria, gram positive (firmicutes and actinomyces), proteobacteria (gram neg), spirochetes, catch all class (euk-like)
47
thaumarchaeota
- mesophiles
- marine environments
- known mainly from DNA
- signature: tetraether lipid
- ammonia oxidizers
48
crenarchaeota
- barophilic vent thermophiles
- sulfolobus (require O2, pH 2-3, secretes toxins)
- ignococcus (unusual cell architecture)
49
lokiarchaeota
- deep sea
- share many traits w euks
- DNA sequence known
50
euryarchaeota
- soil and water
- associated with plants and animals
- wide range of metabolic capabilities
- include halophiles
- methanogens
- some HGT with crenarchaeota
51
what is involved in classical microbiology?
- collect sample
- bring back to lab
- dilute and plate
- characterize colonies that grew
52
what is involved in bioinformatic microbiology?
- collect sample and bring back to lab (size matters)
- extract DNA (make sure environmental contaminants are removed
- prepare libraries of all rRNA genes
- sequences using NGS
- use computer programs to analyze
53
what are the various rRNA genes we use for sequencing?
- 16s rrn in bacteria
- 16s rrn with variations in archaea
- 18s rrn in euks
- all have both conserved and variable regions
54
what can NGS be used for?
- small RNA profiling (miRNA)
- targeted sequencing of genome regions
- whole genome sequencing
- transcriptome sequencing or quantification
- ribosome profiling
- epigenetics > CHIP-seq (histones) and DNA methylations
55
how does one perform NGS?
- barcode all of your primers
- fragment your genomic DNA and throw on adapters
- allow for library hybridization and then bridge amplification (get amplified clusters)
- sequence your library and collect the data
- align data and determine your sequences in each cluster
56
when considering functional bacterial ecology, where do most bacteria fall in the food web?
decomposers
57
mutualism
two organisms grow in an intimate species-specific relationship in which both partner species benefit and may fail to grow independently
58
synergism
both species benefit through growth, but the partners are easily separated and either partner can grow independently of the other
59
commensalism
one species benefits, while the partner species neither benefits nor is harmed
60
amensalism
one species benefits by harming the another, the relationship is nonspecific
61
parasitism
one species (parasite) benefits at the expense of the other (host), the relationship is usually obligatory for the parasite
62
provide an example of mutualism
lichen growth on stone monuments
- cyanobact make energy and provide CO2
- algae provide protection
- fungi provide minerals for growth
this is mutualism bc if they were all just trying to grow by themselves on barren rocks they would quickly die
63
provide an example of synergism
the gut microbes
- can grow independently
- can provide nutrients to each other in the same vicinity
64
provide an example of amensalism
actinomycetes (mainly streptomyces) in soil
- produce compounds (antibiotics) that kill other bact nonspecifically
- the actinomycetes catabolize the dead bacteria
65
what are some important things our gut microbiome does for us?
- digests food and feeds compounds to human cells
- makes nutrients we need but don't make (B vitamins)
- communicates with the body in a variety of ways
- influences basic pathways in humans (including human brain)
66
why do the nitrogen cycles of all ecosystems require bacteria?
earth's major reservoir of N2 is in the atmosphere, the only biotic processes that fix N2 into biomass and then return N2 to the atmosphere are done by bacteria (this is assimilation)
67
what are questions to ask when considering biogeochemical cycles?
- how much is in each component
- how available is each component
- how do the components fit together
- are the components bio? geo? chem?
68
what is the major oxidation state of carbon used by all life?
- 0 oxidation state
- carbohydrate (CH2O)n
69
what are the various fates of CO2?
- ocean absorbs CO2 as carbonates
- photosynthesis traps CO2 in biomass
- plants and microbes sequester CO2
- fossil fuels release CO2
- microbial decomposition releases CO2
70
what are the two parts of our immune system?
- innate immunity
- adaptive immunity
71
what are the 3 key questions to ask when considering a potentially pathogenic microbe?
- who are the microbes?
- how many are there?
- where'd they come from?
72
what is a nosocomial disease?
a bacterial infection that one is more likely to get in a hospital
73
overview of the aspects of the innate immune system
- physical barriers (skin, mucous membranes)
- chemical barriers (stomach acid)
- nonspecific cell interactions
- hardwired, you are born with it
- present at birth before exposure to microbes
74
what are the 3 blood cell types?
white, red, platelets
75
what are the cells of the innate immune system?
all white blood cells
- PMNs (polymorphonuclear leukocytes)
- monocytes
- macrophages
- dendritic cells
- mast cells
76
what are the different types of PMNs?
eosinophils - stain w acidic dye (eosin), release proteins and small molecules that are toxic to microbes
basophils - stain w basic dyes, release proteins and small molecules that are toxic to microbes
neutrophils - most abundant white blood cells, performs phagocytosis
77
what do monoblast cells turn into?
monocytes, macrophages, dendritic cells
78
characteristics of PMN's
- aka granulocytes
- multilobed nuclei
- lysosomes are enzyme rich
79
what are neutrophil extracellular traps?
- after an interaction with a microbe, neutrophils undergo NETosis (they lyse and release their DNA)
- neutrophil DNA laced with antimicrobial compounds that surround microbes
- NET traps microbe, compounds from DNA kill microbe
80
what are the downfalls of NETs?
- can result in autoimmune disorders if cells accidentally take up antigens for the body
- the release of cellular contents can be extremely harmful
81
things to know about monocytes
- perform most phagocytosis
- circulate in blood vessels
- can migrate out of blood vessels and into tissues
- differentiate into macrophages (first contact w microbes, antigen presenting cells) and dendritic cells (present in spleen and lymph nodes, antigen presenting cells)
82
natural killer cells
- kill infected euk cells with bact inside, look for cell surface changes
- looking for protein complexes on cell surface (MHC class I and class II)
- perforin produced by NK cells puncture the membrane of target cells resulting in bursting
83
what type complement pathway is associated with the innate immune system?
the alternative complement pathway
84
what type of complement pathway is associated with the adaptive immune system?
- classic pathway
- lectin activated pathway
85
what are the 3 populations of cells involved in the adaptive immune system?
B cells, NKT cells, T cells
86
what is a humoral adaptive immune response?
- antibodies directly target microbe
- recognize antigens
- antibodies specifically go coat the virus and block virus receptor proteins
87
what is a cell mediated adaptive immune response?
- T cells recognize microbes and destroy infected euk cells
- recognize antigens
88
what can antigens be?
DNA, proteins, RNA, sugars, lipids, usually very small bit which is actually recognized
89
what types of cells are antigen presenting cells (APCs)?
macrophages and dendritic cells
90
what are the cell-cell interaction steps involved in making antibodies?
1. APC engulfs microbe and puts antigens of the microbe on its surface
2. APC travels to a nearby lymph node and presents the antigen to a specific T cell, which recognizes the antigen and becomes activated
3. activated T cell links to B cell that has bound the same antigen
4. B cell is stimulated to generate a plasma cell that secretes antibody against the antigen
91
what are the 5 types of antibodies?
- IgM, IgG, IgA (secretory dimer), IgE, IgD
92
list the 5 types of antibodies and their functions
IgM - main antibody of primary responses, best at fixing complement; the monomer form of IgM serves as the B cell receptor
IgG - main antibody of secondary responses, neutralizes toxins, opsonization *best memory and most prominent
IgA (secretory dimer) - secreted into mucus, tears, saliva, colostrum *poor memory
IgE - antibody of allergy and antiparasitic activity
IgD - B cell receptor; monomer of IgM
93
what cells are used for short term vs long term immune memory?
short term - activated T cells
long term - long-lived memory B cells
94
what are the steps to making antibodies from genes?
1. recombination in germ-line DNA joins D and J segments
2. recombination joins V segment to DJ segment
3. transcription and RNA splicing removes J segments beyond VDJ joined segment and sometimes the u constant region
4. heavy chain peptide is made with either the u or delta constant region
5. light chain peptide is formed by separate recombination events
6. antibody is formed
95
why is the creation of antibodies from genes one of the most wasteful processes in biology?
the creation of functional antibodies relies on 3, specific, separate recombination events, this is highly unlikely with the makeup of the gene itself, the recombination is never perfect, only about 10% of made antibodies are functional
96
what prevents self-recognizing antibodies from circulating in the body?
the thymus
97
what class of MHC receptors are recognized which cells?
MHC I - recognized by CD8 T cells (become natural killer T cells)
MHC II - recognized by CD4 T cells (become helper T cells)
98
what are the phases of the adaptive immune response?
- antigen recognition
- lymphocyte activation (differentiation and clonal expansion)
- antigen elimination (humoral immunity and cell-mediated immunity)
- contraction (homeostasis) (apoptosis)
- memory
99
what are the different activation methods of the complement pathway?
classical activation (adaptive immunity) - antibody is activator
alternative activation (innate immunity) - LPS is activator
lectin activation (immune system independent) - lectin is activator
100
steps of classical (adaptive) activation of complement pathway
1. C1 complex binds Fc region
2. C1 complex cleaves C4 and C2, whose fragments rejoin to make C3 convertase
3. C3 convertase cleaves C3 to C3a + C3b joins with C3 convertase to make C5
4. C5 convertase cleaves C5 to C5a + C5b
5. C5b leads to formation of the membrane attack complex
6. C5b starts to form a prepore complex by binding to C6 and C7
7. the resulting C5bC6C7 complex binds to membrane, finally C8 and C9 factors join to form the membrane attack complex (MAC), becoming a destructive pore in the membrane of target cell
101
steps of alternative (innate) activation of complement pathway
1. C3 spontaneously cleaves slowly into C3a and C3b
2. if C3b contacts LPS on an invading gram neg microbe, the bound C3b becomes stable and binds another factor designated a factor B
3. factor B is now susceptible to cleavage by yet another protein, factor D
4. the resulting complex, called C3bBb, is changed into C5 convertase by properdin, another serum protein
5. C5 convertase cleaves C5 into serum C5a and C5b
6. C5b starts to form a prepore complex by binding to C6 and C7
7. the resulting C5bC6C7 complex binds to membrane, finally C8 and C9 factors join to form the membrane attack complex (MAC), becoming a destructive pore in the membrane of target cell
102
what bact is responsible for lyme disease in nearly all US cases?
Borrelia burgdorferi
103
what tick species carries lyme disease bacteria? (B. burgodorferi)
Ixodes scapularis (east coast) and Ixodes pacificus (west coast)
104
are there free living B. burgdorferi?
no, obligate intracellular parasites
105
how are the reservoirs and hosts determined for ticks?
by the size of host and size of blood meal for the tick
106
maybe go through the enzootic cycle later for ticks/Borrelia to look at types of hosts
107
characteristics of Borrelia
- internal flagella (endoflagella, lives in periplasm) give them their spirochete shapes
- flagella used to propel bact into distal tissues including heart and joints
- flagella allows bact to swim to very viscous media
- the endoflagella is hidden from host immune system
108
are deer infected with Borrelia
no, deer are reservoir incompetent hosts, they move infected ticks around but do to become infected
109
why is Borrelia an obligate intracellular parasite?
- doesn't make toxins or specialized secretion systems or LPS (does make lipoproteins)
- disease factors are bacterial products needed for the bact to grow and survive
110
what are some characteristics of Borrelia?
- small genome compared to other bact
- 1 linear chromosome that is very stable and contains housekeeping genes (pols, gyrase, etc)
~ 17 plasmids which contain unique, duplicated, and mutated genes
- no TCA cycle, nucleotide synthesis, or fatty acid synthesis
111
steps to a tick bite
1. penetrate epidermis with their mouth parts
2. digest tissue and prevent repair
3. dilate capillaries/vascular dilation
4. prevent coagulation of blood
5. dampen immune system
6. prevent pain
112
how do ticks dampen the immune system?
- make proteases to dampen mast cell response
- chemokines to block neutrophils
- make cmpd that mimics macrophage inhibitory factor
- binds to C3 to prevent formation of C5
- interferes with APCs
- suppresses cytokines
- suppresses B cells
113
talk about how Borrelia gets into a tick gut
114
talk about how Borrelia move out of tick gut
115
what aids with long-term Borrelia infections?
- the surface protein VsIE changes constantly, various cassettes which can be placed together, this gene that makes a lipoprotein is so obnoxiously variable we can never really fight it
116
what are the different types of infection routes?
- horizontal transmission: direct
- horizontal transmission: indirect
- vehicle transmission
- vertical transmission
- insect vectors
117
why must pathogenic microbe have pilins, some way to adhere to our cells?
they must be able to replace existing microbes, most microbes we ingest simply exit
118
what are the 4 types of Pili
lol just Types I-IV
119
maybe look at all different types of Pili
Type I: cause urinary/kidney infections
Type II: across both membranes, may play roll in pathogenesis or metabolism
Type III: allows direct injection of toxins into Euk cell cytoplasm by forming a channel between bact and host cell
Type IV: reach out and grab something
120
what are non-pilin molecules that allow bact to bind to Euk cells
adhesins and biofilms
121
what are the known mechanisms of toxins which are secreted by bact to affect Euk cells?
- plasma membrane disruption
- cytoskeleton alterations
- protein synthesis disruption
- cell cycle disruption
- signal transduction disruption
- cell-cell adherence
- vesicle traffic
- exocytosis
- superantigens
122
types of plasma membrane disruptions
- pore-forming
- phospholipase
- vacuole escape
123
what bact causes protein synthesis disruption?
Corynebacterium diptheria - making diptheria toxin
124
what is shiga toxin?
induces DNA damage which activates G2 inhibitors (cell cycle inhibitor)
125
various reasons why we have so many diseases today
travel, drug resistance, food industry, agr industry, human susceptibility and behavior
126
name 4 major infectious microbe
- staphylococcus aureus
- mycobacterium tuberculosis
- rhabdoviruses (rabies)
- prions
127
go through staph infection
128
go through tuberculosis infection
129
go through rabies infection
130
prions are horrifying, elaborate
131
what characteristics make up an ideal antibacterial?
- selective, unique target
- bactericidal (kills)
- narrow spectrum (doesn't kill normal flora)
- high therapeutic index (ratio of toxic level:therapeutic level)
- few adverse reactions (not toxic or allergen)
- various routes of administration possible (IV, I’m, oral)
- good absorption
- good distribution to site of infection
- emergence of resistance is slow
132
how do we do selective targeting of antibiotics?
must inhibit bact but NOT euks by
- exploiting differences in enzymatic structure
- exploiting differences in membrane permeability
- exploiting differences in antibiotic modifications inside the cell
133
what are lead compounds? what do they contribute to different generations of antibiotics?
134
what do bactericidal vs bacteriostatic refer to?
whether a antibiotic will kill a bacteria or simply stop its growth
135
what is a therapeutic index?
the range between efficacy and toxicity
- we want the largest difference between them that we can get
136
how do we measure antibiotic effectiveness?
MIC - minimum inhibitory concentration
137
what processes do antibiotics inhibit?
- cell wall synth, cell membrane integrity, DNA or RNA synth, protein synth, metabolism
138
why are antivirals traditionally kind of sucky?
too much variation in viruses
139
are the 4 groups of antivirals used to treat HIV?
- reverse transcriptase inhibitors
- integrase inhibitors
- protease inhibitors
- entry inhibitors
140
basically antifungals suck, actually a big problem
141
why do we have so much antibiotic resistance?
- over prescribing
- treating them as wonder drugs
- not able to find more lead compounds
- we are capitalist society, we don't invest as much in short term antibiotics as we do in long-term medications
142
what are the clinical trial stages for new antibiotics?
stage I - will it kill people?
stage II - is it even effective? doing what we said?
stage III - does it behave in large groups of people?
143
ways to ID bacteria
growth on specific media, reactions to stains/microscopy, biochemistry, PCR
144
two ways to ID infectious organisms
- ELIZA overnight assays (bunch of antibodies)
- SNAP test (with specific antigens)
145
what does epidemiology do
examines disease frequencies and distributions in human populations
