Microbiology Lecture Notes - Viruses, Bacteria, and the Microbiome

Summary

These are lecture notes on microbiology. The notes cover topics such as viruses, bacteria, archaea, genetics, the human microbiome, and their interactions. Key areas covered include viral infections, bacterial pathogens, the gut-brain axis, and the role of the microbiome in health and disease.

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Week 1 All main points avian influenza virus - clumping of red blood leads to cells (H) hemagglut...

Week 1 All main points avian influenza virus - clumping of red blood leads to cells (H) hemagglutinin viral surface glycoprotein - : , neuramindase : cleaves sialic acid that inhibits hemagglutination (N) - mostly infects aquatic birds - mutations + adaptations why need new vaccines each ongoing year - are we tar neurofibrillary alzheimers disease comes from aggregate protein that causes tangles drift gradual change in mutations to adaptations antigenic leading : + variations antigenic shift : Virus undergoes a sudden change in genetic makeup creating a new strain arms race : Our immune system learns from pathogens & pathogens learn about US bacterial food poisoning food poisoning isn't from one singleagent - gastroenteritis Stomach flu > - long lasting diarrhea - : symptoms are not the same in every case - loss of fluids is very - common bearer fever is a pathogen found in mountain stream water broad specificity pathogens capable of infecting a wide range of host species : on the bacteria surfaces ↳ adhesive fimbriae grab onto particular glycoproteins ↓ glycolipids on our all surfaces H INI : Spanish flu back then today's , swine flu Corona Sars-CoV-2 - Viral spike (5) protein binds to ACE2 all surface receptors could've been bat reservoir and intermediates pangolins as - ebola virus - negative SSRNA fruit bats are reservoir - -highly transmissible - hemorrhagic fever Virus an organism at biochemical equilibrium is dead 1st law of bio : all living organisms obey the laws of thermodynamics (chem + phys) > - 1st corollary life requires the creation of order (decreases : entropy > - 2nd corollary an organism at biochemical es is dead : HIV & human immunodeficiency virus RNA enveloped lentivirus - mutation rate due to retrovirus mechanism (faulty RTase) -very high homology : descent from a common ancestor stopped spread of BSE by banning certain animal parts from entering the food chain marburg transmitted to humans is by the consumption of bushmeat or direct contact pigs have 2 receptors : I that binds avian viruses + I that binds human viruses influenza virus fast evolution : multiple viral chromosomes allow recombination when - infecting the same cell - usually negative SSRNA krrw was passed btwn people who practiced cannibalism virus marburg - enveloped RNA filovirus hemorrhagic fever virus - contact w/ of bats or injection green monkeys - or MERS (middle eastern respiratory syndrome) needs intermediate host , most likely camel - an a -transmission was relatively limited most common protozoan food poisoning toxoplasma - - cryptosporidium toxo-cryp-gia giardia - most important pathogens for foodborne illnesses bacteria - - viruses prions - protozoans - most influenza Viruses appear to havean origin natural selection appears at both phenotypic + genotypic levels non human primates are susceptible to HIV & Zika Virus noroviruses are common in oysters + seafood physical laws : no system can exhibit perpetual motion pigs are a massive location for viral recombination prion diseases are transmissible spongiform encephalopathies (TSEs) or protein aggregates prion diseases to fold cause other normal proteins incorrectly like chain reaction - a - BSE led to mad cow disease where be found Centire peyer patches intestine - are major prion proteins can for cows) prion diseases make cellular protein go from correct alpha fold to incorrect beta fold 2nd law of life enclosed in biology all is membranes : 1st covollary the cell is the only structure that can growt divide its - : on Own 2nd life is corollary : all programmed by cellular genetics instructions - swine influenza virus pigs have 2 receptors - materiala create virulent strains pigs can swap their genetic - more - considered mixing bowls of influenza virus first 2 laws of thermodynamics 1. energy cannot be created or destroyed closed. 2 entropy of a system always increases the replicase , RNT dependent RNA polymerase does not have a good proofreading capability 3rd law of biology all living organisms arose in an evolutionary process : 1st corollary all living organisms have homologous macromolecules - : 2nd corollary genetic code is universal for all organisms on earth - : influenza is transmitted from bird -> pige human viral food poisoning less - common - most costly a to detect hardest to treat virus recombination - rotavirus - 2 gastroenteritis norovirus - - bats are often original host virus recombination : two related Viruses , when in the same host , have the ability to mix their genetic material + become more virulent mutants bats , primates + rodents have higher proportion of zoonotic diseases Al- > Avian influenza virus mad cow disease is the mutated human variant of BSE gram positive bacteria is most common type of bacteria for food poisoning RNA viruses evolve faster than DNA viruses be RNA is less stable + DNA has access to host proofreading Week 2 P2 is the most important for determining the type of the amino acid PI is important for the specific amino acid - least negative selection principle important - : What is changes the most alternate wheel based on P2 4 quadrants - I hydrophobic (T/V) I hydrophilic (A) 2 Semi-polar (Gora) - , , I similar amino acids will likely only vary in position wobble base pairing P3 allows specific alternate base pairing : - for start codon (fMet/Mett , wobble is Pl when 43 is important , it only matters whether the position is a purine (AorG) or pyrimidine (Word more H-bonds can be formed between C + G than A + U bonds between tRNA + mRNA are stronger when the tRNA is a purine + mRNA is a pyrimidine all common nonsense codons use V in P - the most common codon , UAA stop , has the lowest H-bonds possible out of all the codons possible stop primordial soup conditions can also give rise to nucleic acids , lipids , + others benefit of redundancy SNP be multiple codons : can code for the amino acid less has chance to same , a change the amino acid identity + cause a problem eukaryotes branched off from asgard archaea episymbiosis : understudied mode of association btwn for CPR bacteria + DPANN archaea microbes especially no cell is an island : genome-resolved metagenomics approaches allow for studying metabolic pathways spanning different species in a community found seafloor sediments asgard archaea vents was in near hydrothermal asgard genomes typically encode eukaryotic systems - MVA lipid synthesis pathway membrane remodeling /trafficking systems - cytoskeletal proteins - ubiquitin ~ vesicle formation systems - CPR : Candidate phyla radiation CPRTDPANN are mostly symbionts + episymbionts episymbiont : symbiont that lives on the surface of another for survival organism radiation : increase in taxonomic diversity that is caused by elevated rates of speciation CPK bacteria lack key biosynthetic pathways classify based on metabolic insights , metagenomics different environments create lineages that diverged early from primitive lifeforms have bacteria of CPR consistently small genomes + cell sizes+ most have a symbiotic lifestyle DPANN Archaed - small cell sizesa limited metabolic abilities unique surface attaching grappling hooks Chamil - non-CPR bacteria can mix aerobic + anaerobic pathways , metabolic - versatility , I can survive in changing conditions - exist in our microbiome fermentation, not photosynthesis - secondary metabolites give insight into lineages > - can CPR DPANN archaea + CPR have slightly diff genetic codes - ↳ also have unusual ribosome compositions be they've missing some "essential" ribosomal proteins are often shared - gaps not shared well w/non-CPR symbiotes gaps - are for CPR + DPANN episymbiosis common associated WI surface of cells , cell to cell contact - pili-like structures that extend from CPR cell surfaces - asgard archaea these archaea share relatively close evolutionary - a relationship w/ eukaryotes , then we saw a fusion of bacterial + archaea cells - many archae genes are considered eukaryotic signature proteins lipid divide all isoprenoids metabolites that are essential in living - : in all domains of life organisms archaea composed of isoprenoid-based lipids , membranes - precursors are made W/ MVA pathway (mevalonate MEP pathway alternate MrA pathway used by - : eukaryotes & archaea MEP not reported in archaea except for wresearch he ofa - lipid divide btwn bacteria + archaea by MVA + MEP - distribution is muddied by these results everything is made , consumed+ digested GABA gamma-aminobutyric acid : lingering questions rapid evolution - reduced genomes tend to increase evolution rates - early divergence - possibly we don't have enough of the missing links - convergent evolution - mostly ruled out bynonoverlap w/ non-CPR - genome-reduced symbionts like buchnera horizontal gene transfer : "borrow" systems from other lineages - BBB : blood brain barrier Asplautism spectrum disorder) is highly multi-factorial (genetic + environmental) there's a connection btwn gastrointestinal (GI) issues + ASD gut microbiota - microbiome strengthens intestinal barrier integrity - microbiota development started at birth - directly or indirectly affect homeostasis - growing evidence shows that dysbiosis can cause several diseases a disorders such as ASD metabolism microbiota produces many metabolites - Short chainFatty - acids/SCFAs) can act on the CNS thr the microbiota-gut-brain-axis - tryptophan can be intoconverted a metabolite that generates neurotoxic products depending on changes to microbiome ANS : automatic nervous system ENS : enteric nervous system HPA adrenal axis hypothalamic pitrary - : - ANS , ENS , HPA communicate via Vagus nerve to mediate connection gut-brain neurotransmitters (NTs) - metabolites from microbiota cross BBB levels of NTS + change - GABA is not able to cross the BBB + only acts locally maternal microbiota - maternal gut microbiota modulates growth & fetal brain development - vertical transmission of microbiomes , birth method can have Significant differences in microbiome diversity epigenetics change acetylation& deacetylation - deacetylation = gene inhibition by condensing the chromatin - - histone deacetylases (HDACs) are targets of microbiota-derived metabolites - ASD postmortem brain samples show abnormal alternative of mRNA splicing BBB - maternal gut microbiota influences fetal BBB , where it can upregulate the expression of fight junction proteins food selectivity picky eating+ severe food selectivity (FS) in ASD patients - consumption of particular diets alters gut microbiota to - favor specific bacterial genera - less-diverse diet could reduce microbiome diversity social interactions - deficits in social behavior which can be reversed by probiotics or microbiota recolonization germ free(GF) animals GF mice have social behavioral problems compared to normal - mich probiotics species of : live microorganisms that provide health benefits to the host upon ingestion prebiotics non-digestible : fiber compounds that act as a substrate for the growth of beneficial microbes symbiotics : contain a combination of specific probiotics + Suitable produce similar beneficial effects in prebiotics may ASD fecal microbiota transplantation (FMT) when given to children ASD symptoms are greatly reduced as - , well as Gl problems biomarkers butyric acid , a SCFA , has proinflammatory function of - intestinal macrophages , regulate BBB permeability zonulin levels got fight junction stabilizing protein were : - - upregulated in ASD children therapeutics - no universal treatment as of yet significant heterogeneity - microbial products cause differences in neurodevelopment excessive inflammatory products , IL-6 , can cause abnormal & retardation nevron outgrowthhas inhibiting IL-6 reversed abnoralities in offspring prenatally - exposed to maternal immune activation (MIA) normal microbes required for upkeep of the intestinal lining tight - can inhibit IL-6 Junctions altered BBB allows in inflammatory cytokines+ causes neuro inflammation kids w/ autism suffer from various GI issues , such as IBD + many Crohn's disease disruption of the mucosal microbiota has been extensively in ASD children reported leaky gut" : where cytokines from the gut can get into the bloodstream then the BBB + pass be the true force for survival cooperation may driving - evolution microbiota in most plastids in plants + major eukaryotic subdivisions arose via initial endosymbiotic events from cyanobacteria - proteobacteria bacterial parasites - B bacteriovirus. : Bba B exovorus : Bex > -. parasitic modes - Bba grows in peraplasm of the prey cell Bex grows externally - both Bba & Bex contain large numbers of pseudogens + incomplete systems Bba life cycle 1 attack. 2 Outermembranepenetration 3. periplasmic growth phase (no division). 4 final synchronous cell division stage together wh a host cell lysis Boelloplast is the single snake-like multi-nucleoid cell Bex outside theall grows completely divide by fission Bex a grow binary Bex has smaller genome than Bba archael symbiotic species - nanoarchaeum equitans novel small type of archaeon was : discovered in apparent symbiotic relationship w/ different , larger sized , archael species can only co-culture wh Ignicoccus species - metagenomics + CPR - CPR has self-splicing introns - metagenomics restated the DNA of entire communities of bacteria : sequenced who separation of the different are simultaneously from each other species asgard - small cells depend cooperative symbiotic relationships on of flow reverse model updated symbio-genetic model for the origin : > - eukaryotes that involves electron or hydrogen flow from an organoheterotrophic archael host to a bacterial symbiont there's much greater diversity of the bacterial domain that suggests that bacteria were the first inhabitants on Earth life form could have full complement of metabolic no primordial a F biosynthetic catalytic proteins that would allow living organisms to reproduce in the presence of only abiotic sources genetic recombination + interspace gene transfer mediated by , transposons + plasmic like elements since evolution tends towards complexity , suggested symbiotic relationships provide a potential pathway for creation of more complex organisms given credit for the 3rd law of darwin is biology entropy of a closed system always increases Viruses can use RNA DNA is much more stable , good tradeoff CPR nano-bacteria + nano-archaea look similar both associated w/ much larger microbes - episymbionts - small small size genomes a - must be certain obligate : a way facultative : has preference but can survive in either aerobe : Oxygen-dependent anaerobe oxygen-independent : obligate anaerobe : no growth in oxygen obligate acrobe : growth in oxygen who oxygen but prefers having : facultative anaerobe can grow Oxygen facultative derobe grow w/ oxygen but prefers no oxygen : can lamack : soft inheritance or lamarckism first of acquired characteristics theory R ↳ disuse for characteristics use a phenotypic organs become specially developed as a - when certain result of environmental need , then that state of development is hereditary a can be passed on to progeny bioinformatics : every detail of organism is encoded, deciphered + rendered evolution is a guide thou which biology makes sense most reliable for function molecular phylogeny is guide ↓ mechanisms + phenotype the microbiome is multiple microbiomes , one in each tissue of the each tissue microbiome influences healthy activity tissue innate immune system fast+a general : adaptive immune system slow specific: kill the commensal immune system may accidentally bacteria when to trying kill pathogenic - beneficial = commensal virulent pathogenic - = the microbiome reinforces barrier immunity of the host - host minimizes contact btwn the microbes + the epithelial surface to limit inflammation mucosal firewall formed to keep invaders out - mucus line is the first defense against pathogens antimicrobial peptides produced from the epithelial cells is - second defense - macrophages is third line of defense microbiota highly dynamic - correlated WI density host immunity - - protects from inflammatory disorders - also acts via GBA (gut brain axis) human gut - if this system breaks down , one can end up w/ inflammatory diseases like IBD - multifactorial microbiota causes inflammation disease that change in - then affects the microbiota again diet , microbiota , immunity = interdependence triangle got lumen : lumen is the inside space of a tubular structure like the artery intestine or. it means opening biochemical btwn the Gl ta gutbrainaxis signaling : - connected via vagus nerve BBB helps keep brain free of pathogens - right junctions - - zonulin protein reinforces the fight junctions of blood vessels in BBB cells surround blood cells BBB glial in - - immune system in brain is different than the rest of the body dietary & environmental stress alter Gl microbiota 80% of serotonin is made in the gut while 20% is made in the brain some microbes make metabolites like butyrate , which of cells in BBB can alter activity #↳ affects stress levels purines have I aromatic rings pyrimidines have I aromatic ring not all A T : binding or C: T binding are equivalent in energy 42 has least amount of variance , most conserved position key positions = P2 specifies type of amino acid T hydrophobic - = A hydrophilic - = CtG semipolar - = PIspecifies identity of amino acid - - P3 is wobble position except , in initiation - for initiation , wobble is PI not P3 termination - all U to start pyl pyrrolysine - = sec seleno-cysteine - = leucine is most resistant to non-synonymous mutations Pyl in archaea + bacteria See is in all domains of life A T : + T : A , G : c + C G : - depends what is the +RNA or what is the mRNA T mRNA : A = : tRNA is stronger than other way around C:G MENA +RNA is stronger = : there are eukaryotic-like genes that are found inside archaea eukaryotic specific proteins found in nanobacteria most aerobic-like pathways are obligate anderobes I cannot tolerate oxygen MVA in archaea/eukaryotes , MEP in bacteria lipid divide - exist sporadic exceptions - mutation is most important - cooperation can be asimportant as competition vast diversity in microbial life prokaryotes complete C, N , S fixation cycles decomposition photosynthesis interactions such species specific as mutualism 3 mainhouse gases Carbon dioxide (CO2) - - nitrous oxide (N20) methane (CHP) -