Micro Final Review PDF

Exam 1 Chapter 1 + 19: Evolution of Microorganisms and Microbiology Members of the Microbial World - Relatively simple in their construction and lack of highly differentiated cells and distinct tissues Acellular Infectious Agents - Viruses - Viroids and virusoids - Prions Last Universal...

Exam 1 Chapter 1 + 19: Evolution of Microorganisms and Microbiology Members of the Microbial World - Relatively simple in their construction and lack of highly differentiated cells and distinct tissues Acellular Infectious Agents - Viruses - Viroids and virusoids - Prions Last Universal Common Ancestor (LUCA) - Universal phylogenetic tree - relatedness, but not time of divergence, determined this way - Archaea and Eukarya evolved independently of Bacteria - Archaea and Eukarya diverged from common ancestry Evolution of Cellular Microbes - Mutation of genetic material - New genes and genotypes evolved - Bacteria and Archaea increase genetic pool by horizontal gene transfer Microbial Species - Bacteria and Archaea do not reproduce sexually and are referred to as strains - Species is a collection of strains - Strains are descended from a single, pure microbial culture  - vary from each other a) Biovars - differ biochemically and physiologically b) morphovars - differ morphologically c) Serovars - differ in antigenic properties - type strain is the first studied Discovery of Microorganisms - Earliest microscopic observations by: - Robert Hooke: published drawings of the fungus Mucor in his book, Micrographia, in 1665 - Antony van Leuwenhoek: first person to observe microorganisms accurately Swan Neck Experiment Limitations of Koch’s Postulates Chapter 3: Bacterial Cell Structure Surface Area to Volume Ratio - The larger the SA/V ratio, the more easily nutrients can move - collision surface area - Small cells are more effective transporters - As cell size increases the surface area to volume ratio decreases and thus transport is less effective - SA=4pir^2, V= 4pir^3/3 Examples of Bacterial Cytoskeleton Molecules - FtsZ - many bacteria; tubulin homologue - MreB - many rods; actin homologue - CreS - maintains curve shape; intermediate filament homologue Inclusions - Gas Vacuoles - Magnetosomes - Cytoskeletal protein MamK - Model bacteria: Magnetospirillum gryphiswaldense Plasma Membrane Functions - Encompasses the cytoplasm; absolute requirement for all living organisms! - Selectively permeable barrier - Interacts with external environment - receptors for detection of/and response to chemicals in surroundings - transport systems - metabolic processes Bacterial Lipids - Saturation level reflect environmental conditions - Bacterial membranes lack sterols, contain hopanoids - Eukaryotes have sterols in their membranes - usually absent in prokaryotes Methods for Uptake of Nutrients - Some nutrients enter by passive diffusion - Transport mechanisms a) Facilitated diffusion b) Active transport c) Group translocation Bacterial Cell wall - Cell wall functions a) Shape b) Protection c) pathogenicity - Peptidoglycan (murein) - two types based on gram stain a) Gram positive b) Gram negative Gram Positive Cell Walls - Teichoic acids - Exoenzymes - Periplasmic space Gram Negative Cell Wall Basic Structure - Outer membrane - lipopolysaccharide (LPS) - No teichoic acids!! - Braun’s lipoproteins - Porin LPS (LipoPolySaccharide) - Three parts 1) Lipid A 2) Core polysaccharide - KDO (2-keto-3-deoxy-octanoate) 3) O side chain (O antigen) Mycobacteria - Mycolic Acid - Acid fast staining - M. leprae - M. tuberculosis Atypical Bacteria - Cannot be stained by Gram stain procedures or are too small - Includes obligate intracellular pathogens - Rickettsia spp. Has a permeable membrane, pleomorphic - Chlamydia spp. Does not synthesize ATP by itself - Mycoplasma spp. Does not have a cell wall Cells that Lose a Cell wall - Lysozyme vs Penicillin - Removal of the cell wall - protoplasts - Gram positive - spheroplasts - gram negative - L-form  - Bacillus anthracis, Treponema pallidum, Mycobacterium tuberculosis, Helicobacter pylori, Rickettsia prowazekii, and Borrelia burgdorferi Components Outside of Cell Wall - Capsules - polysaccharides - Protective advantages a) Resistant to phagocytosis b) Protect from desiccation c) Exclude viruses and detergents - Slime layer - gliding motility Flagella - Functions - motility and swarming behavior - attachment - virulence - Patterns of flagellation a) Monotrichous b) Lophotrichous c) Amphitrichous d) peritrichous Motility - FIve major types: 1) Flagellar movement (swimming) 2) Swarming 3) Spirochete motility 4) Twitching motility 5) Gliding motility - Bacteria and Archaea have directed movement - Chemotaxis Bacterial Endospore - Complex, dormant structure - Resistant to numerous environmental conditions - Includes:  - calcium (complexed with dipicolinic acid, Ca-DPA) - small, acid-soluble, DNA-binding proteins (SASPs) - dehydrated core - spore coat and exosporium protect - By Bacillus, Clostridium and Sporosarcina (cocci) - all are Gram positive Chapters 4, 5, & 6: Archaeal, Eukaryotic & Acellular Microorganisms Archaeal Membranes - Isoprene units - Ether Linkages - Monolayer structure Archaeal Cell Envelopes - S layer - Capsules and slime layers - Pseudomurein - N-acetyltalosaminuronic acid - N-acetylglucosamine - All L-peptides  - B(1,3)-glycosidic bonds - Only Ignococcus has an outer membrane Pathogenic Fungi - Mycoses - tinea - Five Groups a) Superficial b) Cutaneous c) Subcutaneous d) Systemic e) opportunistic - Dimorphic Fungi Cryptococcosis - Systemic mycosis - Cryptococcus neoformans - Dried pigeon droppings - Inhalation - meningitis in this immunocompromised - mild of pneumonia-like in others Nosocomial Candidiasis - Up to 10% of nosocomial bloodstream infections - mortality- 50% - C. auris - Candida albicans of C. glabrata - normal microbiota - spread by sexual contact - Most infections involve the skin or mucous membranes Malaria - Caused by four species of Plasmodium - apicomplexa  - Vector: mosquito - Life cycle of plasmodial protists a) Sporozoite injected with mosquito bite b) Replicates as merozoite in hepatic cells c) Released, enters erythrocytes and replicates d) Lyses erythrocytes – correlates with fever - Pyrotherapy - Dr.Julius Wagner-Jauregg African Sleeping Sickness - Also known as Human African Trypanosomiasis (HAT) - Commonly by Trypanosoma brucei subspecies gambiense - apicomplexa - reservoir: domestic cattle and wild animals - vector: tsetse flies - VSG switching - antigenic variation Toxoplasmosis - Toxoplasma gondii - apicomplexa - Reservoir: wild rodents, birds, small mammals - Fecal-oral transmission from infection animals - Usually asymptomatic or resembles mononucleosis - tachyzoites cross the placenta and infect fetus, causing serious congenital defects or death Structure of a Virus - Virion size: 10-400 nm - Nucleocapsid - nucleic acid (DNA or RNA) - protein coat (capsid) - envelopes - Spikes or peplomers  - attachment a) Hemagglutinin of influenza virus - Identification - Enzymatic activity a) Neuraminidase of influenza virus - nucleic acid replication Viral Multiplication - Steps are similar between phages and mammalian viruses 1) Attachment to host cell 2) Entry and uncoating of genome 3) Synthesis 4) Assembly 5) release Virion Release a) Nonenveloped viruses lyse the host cell b) Enveloped viruses use budding Infection in Eukaryotic Cells - Cytocidal - HIV-AIDS - Persistent - EBV - mono/Burkitt’s lymphoma - Latent - Varicella - chickenpox/shingles - Transformation - HPV - cervical cancer Bacterial and Archaeal Viral Infections - Temperate phage a) Lytic b) Lysogenic - Prophage  - Lysogenic conversion - Corynebacterium diptheriae, Clostridium botulinum, Vibrio cholerae - Virulent phage Influenza (Flu) - Influenza virus - RNA virus; segmented genome - Four groups A, B, C, and thogoto (tick borne) - Type A - Type B - Subtypes based on hemagglutinin (HA) and neuraminidase (NA) a) Total of 16 NA/9 antigenic forms - 31 possible pandemics - worst pandemic in 1918 killed ~50 million people Antigenic Shift and Drift - Antigenic drift - Antigenic shift Viroids - Circular ssRNAs - Do not encode gene products - Plant diseases Prions - Degenerative diseases in humans and animals a) Scrapie in sheep b) Bovine spongiform encephalopathy (BSE) or mad cow disease c) Creutzfeld-Jakob disease (CJD) and variant CJD (vCJD) in humans - Transmissible spongiform encephalopathies  - via medical procedures, genetic, food - Have no effective treatment Exam 2 Chapter 7: Microbial Growth Reproductive Strategies - Eukaryotic microbes - haploid or diploid - asexual and sexual - Prokaryotes - haploid only - asexual - binary fission, budding, filamentous Example of Chromosome Partitioning - ParA/ParB proteins in C. crescentus - ParA - ParB - ParS - System in almost 70% of 400 sequenced bacterial genomes Vibroid Cell Wall Growth & Cell Shape - FtsZ - MreB - CreS - Antibacterial targets? The Growth Curve - Plotted as logarithm of cell number vs. time - Distinct phases 1) Lag 2) Log/exponential 3) Stationary 4) Death 5) Long-term stationary Measurement of Growth Rate and Generation Time Influence of Environmental Factors on Growth - Most organisms grow in fairly moderate environmental conditions - Extremophiles Osmotic Concentration - Reduce osmotic concentration - mechanosensitive (MS) channels - contractile vacuoles in protists - Increase internal solute concentration - compatible solutes Salinity - Nonhalophile - Halotolerant - Halophiles - Extreme halophiles - Halobacterium spp. pH - Acidophiles - Neutrophiles - Alkaliphiles/alkalophiles Temperature - Microbes cannot regulate their internal temperature - Cardinal growth temperatures  - Terms a) Psychrophiles b) Psychrotolerant c) Mesophiles d) Thermophiles e) hyperthermophiles Oxygen Concentration - Obligate aerobe - Facultative anaerobes - Aerotolerant anaerobes - Obligate anaerobe - Microaerophile Basis of Different Oxygen Sensitivities - Reactive oxygen species (ROS) - superoxide radical (O2) - hydrogen peroxide (H2O2) - hydroxyl radical (OH) - Protective enzymes - superoxide dismutase (SOD) - catalase - peroxidase Biofilms - Most microbes grow attached to surfaces (sessile) rather than free floating (planktonic) - Extracellular polymeric substance (EPS) - Quorum sensing Quorum Sensing Systems - Processes regulated by quorum sensing a) Symbiosis - Vibrio fischeri and bioluminescence in a squid b) Pathogenicity and increased virulence factor - Pseudomonas aeruginosa c) Competence for antibiotic resistance genes - Bacillus subtilis - Interdomain communication  - Rhizobium interactions with leguminous plants for nitrogen fixation Chapter 9: Antimicrobial Chemotherapy The Development of Chemotherapy - Most are antibiotics - Paul Ehrilich (1904) - selective toxicity - dyes to treat African sleeping sickness - Sahachiro Hata (1910) - Salvarsan against Treponema pallidum - Gerhard Domagk, and Jacques and Therese Frefouel (1935) - discovered sulfonamides and sulfa drugs - Prontosil Penicillin - First true antibiotic - Ernest Duchesne (1896) - Alexander Fleming (1928) - Florey, Chain and Heatley (1939) - received Nobel Prize in 1945 Selective Toxicity - Selective toxicity - Therapeutic index - ratio of the toxic dose to the therapeutic dose - larger the index, better the drug Broad vs Narrow Spectrum Antibiotics Penicillins - B-lactam ring - B-lactamase/penicillinase - Transpeptidation - Penicillin V and G against Gram-positive only - Semisynthetic penicillins are broad spectrum - Ampicillin against Gram-negative H. influenzae, Salmonella spp. and S. dysentariae - Resistance to penicillins, including the semisynthetic analogs, continues to be a problem - ~1-5% of adults in U.S. are allergic to penicillin Vancomycin - Glycopeptide antibiotic produced by the bacterium Streptomyces orientalis - Transpeptidation - Gram-positives only - including Staphylococcus, Clostridium, Bacillus, Streptococcus and Enterococcus - Important for treatment of antibiotic-resistant staphylococcal and enterococcal infections - previously considered “drug of last resort” - vancomycin resistant enterococcus (VRE) Aminoglycosides - Bactericidal drugs, all with a cyclohexane ring and amino sugars - bind to 30S - Streptomycin, kanamycin, neomycin by the bacteria Streptomyces spp. - Gentamicin from the bacteria Micromonospora purpurea - used for aerobic Gram-negative Proteus, Escherichia, Klebsiella and Serratia - Aminoglycosides can be toxic and cause renal damage Tetracyclines - Four-ring structure - bind to 30S  - Oxytetracycline and chlortetracycline are produced by Streptomyces spp. Others are semisynthetic - Broad spectrum, bacteriostatic - intracellular pathogens rickettsias, chlamydiae, and mycoplasmas - resistant bacteria include Vibrio cholerae - Black teeth Chloramphenicol - First produced from Streptomyces venezuelae - first broad-spectrum antibiotic - bacteriostatic against most Gram-positive and many Gram-negative anaerobes - bactericidal to sensitive bacteria - Binds to 23S rRNA - Toxic with numerous side effects - aplastic anemia, leukemia, neurotoxin reactions - not allowed in food producing animals! Sulfonamides/Sulfa Drugs - Structurally related to sulfanilamide, a p-aminobenzoic acid (PABA) analog - Folic acid - Selectively toxic due to competitive inhibition - Against bacteria and some protozoa Nucleic Acid Synthesis Inhibition - A variety of mechanisms - block DNA replication - block transcription - Drugs not as selectively toxic as other antibiotics because bacteria and eukaryotes do not differ greatly in the way they synthesize nucleic acids Overcoming Drug Resistance - To fight drug resistance a) Give drug in appropriate concentrations b) Give two or more drugs at same time c) Use drugs only when necessary - Possible future solutions Chapters 13 & 16: Bacterial Genome and Genetic Variation Central Dogma of Molecular Biology - Chapter 13 - DNA is the template for - its own replication - DNA replication a) By DNA polymerase - RNA (mRNA, tRNA, rRNA) - transcription a) By RNA polymerase - mRNA is the template for proteins - translation - by ribosomes Nucleotides - Nucleoside - Nucleotide - Purines - adenine and guanine (PURe As Gold) - Pyrimidines - uracil, cytosine, and thymine Protein Structure - Polypeptides - monomers: amino acid - covalent bond: peptide bond - amino-terminus (N) to carboxyl-terminus (C) - Protein: single or multiple polypeptides - denatured - Proteins may have up to four levels of structure 1) Primary 2) Secondary 3) Tertiary 4) Quaternary DNA Replication - Complementary strand - DNA in most Bacteria is circular - bidirectional replication fro oriC to ter site  - two replication forks Protein Coding Genes - DNA template directs RNA synthesis - Complementary DNA strand (sense strand) has the same nucleotide sequence as mRNA - Promoter is located at the start - Leader sequence is transcribed but is not translated - contains the Shine-Dalgarno - Begins 3’-TAC-5’ with start codon AUG (methionine) - Ends with a stop codon followed by a terminator sequence Transcription - Polycistronic mRNA vs monocistronic mRNA - Reaction similar to replication - RNA polymerase in Bacteria a) Core enzyme (2 alpha subunits, B, B’ and w) b) Sigma factor - Holoenzyme = core enzyme + sigma factor The Genetic Code - mRNA is translated into an amino acid sequence - polypeptide - protein - The rules of the Genetic Code: Rule 1: codons are read 5’ to 3’ Rule 2: codons are non-overlapping, message has no gaps Rule 3: message is translated in a fixed reading frame Translation - Synthesis of polypeptide is directed by the sequence of nucleotides in the mRNA - N → C-terminal - The ribosome is the site of translation - coupled transcription/translation in Bacteria/Archaea - polyribosome Molecular Chaperones - Proteins that help other proteins fold - Including:  - trigger factor, DnaK, DnaJ, GroEL, and GroES - Function: a) Protects the cell from thermal damage - Heat-shock proteins (HSPs) b) Aid in transport of proteins across membranes - SecA Macromolecule Transport - Moves proteins that have not been folded yet - Sec (secretory) system exports and inserts integral protein into the cell membrane - SecY, E, G: transmembrane transporter - SecA: recognizes the signal, ATP hydrolyzing enzyme - SecB: prevents folding of the protein - SecD & F: use the proton motive force for translocation - Exoenzymes - amylase and cellulase Type IV Secretion System - Translocates proteins and protein-DNA complexes - Energized by ATP - Three functional types of T4SS a) Gram-negative pathogens can use them to translocate virulence factors into the host cell b) Can be used to mediate horizontal gene transfer in Gram-positive and Gram-negative c) DNA uptake (transformation) and DNA release Effects of Mutations - Observed as phenotype a) Wild type b) Forward mutation c) Reverse mutation d) Suppressor mutation - Intragenic or extragenic SOS Response - Inducible repair system (global control) - Repair excessive damage - repressor (LexA) destroyed by RecA → activating over 50 genes - RecA protein initiates recombination repair Horizontal Gene Transfer i. Bacterial transformation  - Requires bacteria to be competent - Involves complex similar to TFP and T2SS Ii. Bacterial transduction - Requires a phage a) General vs specialized Iii. Bacterial conjugation - Requires cell-cell contact - Involves a plasmid F+ x F- Mating - A copy of the F factor is transferred and does NOT integrate - plasmid is replicated by rolling circle method - Donor genes usually not transferred Exam 3 Chapter 10: Introduction to Metabolism Microbial Metabolism - Representatives in all five major nutritional types - Cycling of elements - Example: nitrogen cycle - four are solely done by microbes - microbes are part of the other four Energy Units - Calorie (cal) - Joules (J) - 1 cal of heat is equivalent to 4.1840 J of work Standard Free Energy Change - Delta G - Exergonic reactions - delta G is negative - reaction proceeds spontaneously - Endergonic reactions - delta G is positive - reaction will not proceed spontaneously Phosphate Transfer Potential - ATP has a high phosphate transfer potential  - Substrate level phosphorylation (SLP) Redox: Two Half Reactions - Oxidizing reaction and reducing reaction - Acceptor and donor are a conjugate redox pair - Oxidized form + e- = reduced form - Standard redox potential (E0) - volts (V) - more negative E0 = better electron donor - more positive E0 = better electron acceptor Main Electron Carriers - NADH and NADPH accepts two electrons and one proton - FAD and FMN carry two electrons and two protons - flavoproteins - CoQ/ubiquinone transports two electrons and two protons - lipid - Cytochromes use iron to transfer one electron at a time - iron IS part of a heme group - Nonheme iron-sulfur proteins use iron to transport one electron at a time - iron is NOT part of a heme group - Number of transported electrons and protons is important Biochemical Pathways - Pathways can be varied a) Linear b) Cyclic c) branching - Pathways often overlap/feed into each other - complex networks - dynamic pathways monitor changes in metabolite levels (flux) Enzyme Terminology - Catalysts a) Substrats b) products - Composed of a) One or more polypeptides b) One or more polyypeptides (apoenzyme) and nonprotein components (cofactor) forming the holoenzyme - Cofactors a) Prosthetic group b) coenzyme Allosteric Regulation - Reversible - Allosteric effector - Regulatory site - positive effector - negative effector - Most regulatory enzymes Feedback/End-Product Inhibition - Pacemaker enzyme - Isoenzymes - Each end-product can regulate a) Its own branch b) Initial pacemaker enzyme Chapter 11: Catabolism: Energy Release and Conservation Nutritional Types of Organisms - Carbon Source - Heterotrophs use organic molecules, which often also serve as energy source - Autotrophs use single carbon molecule - Energy Source - Phototrophs use light - Chemotrophs obtain energy from oxidation of chemical compounds - Electron Source - Lithotrophs use reduced inorganic substances - Organotrophs use organic compounds Electron Donor Matters - Chemoorganotrophs can do 1) Fermentation 2) Aerobic respiration 3) Anaerobic respiration - Chemolithotrophs can only do  1) Aerobic respiration 2) Anaerobic respiration Respiration - Respiration involves the use of an electron transport chain (ETC) a) Aerobic respiration - Acceptor is Oxygen b) Anaerobic respiration - Exogenous acceptor such as NO3, SO4, CO2, Fe3, or SeO4 - Proton motive force (pmf) is generated - oxidative phosphorylation (OP) Fermentation - Endogenous electron acceptor - example: pyruvate - Does not involve the use of an ETC or the generation of a pmf - NO Oxidative Phosphorylation!! - substrate-level phosphorylation (SLP) Energy Sources - Many different enerflgy sources - Most pathways generate glucose or intermediates - must still synthesize the glycolytic intermediates Central Metabolic Pathways - Provide the precursor metabolites to all other pathways - Three common routes: 1. Embden-Meyerhof pathway (EMP, glycolysis) 2. Entner-Duodoroff pathway (ED) 3. Pentose phosphate pathway (PPP) - All three pathways - convert glucose to glyceraldehyde 3-P  - glyceraldehyde 3-P is oxidized to pyruvate the same way in all three pathways Tricarboxylic Acid Cycle - Citric acid cycle of Krebs cycle - Common in aerobic bacteria, free living protozoa, most algae, and fungi - Source of carbon skeletons for use in biosynthesis - Yield per glucose: a) 6 molecules of CO2 b) 8 molecules of NADH c) 2 FADH2  d) 2 GTP or ATP ETC - Makes most of ATP as NADH and FADH2 are re-oxidized - Series of e- carriers - Reminder: - flavoproteins (Fp): 2 electrons and 2 protons - ubiquinone (UQ): 2 electrons and 2 protons - cytochromes: 1 electron - nonheme iron-sulfur proteins (FeS): 1 electron - proteins exist in a multiprotein complex called the oxidoreductases/oxidase Bacterial and Archaeal ETCs - Prokaryotic vs Eukaryotic ETC a) Location b) Different electron carriers c) May be branched d) May be shorter e) May have lower P/O ratio Common Microbial Fermentation - Fermentation pathways are named after the major acid or alcohol produced 1) Mixed acid fermenters (E. coli) 2) Butanediol fermenters (Serratia) 3) Alcoholic Acid fermenters - Includes products: - that lead to food spoilage - making of alcoholic beverages - making of yogurt - making of cheese - making of bread - fuel Chemolithotrophy - e- released from inorganic molecule: - H2, reduced nitrogen, reduced sulfur and Fe2+  - Must use another molecule as carbon source - Terminal e- acceptor - oxygen, sulfate, and nitrate - ETC used, ATP synthesized by OP - NOTE: they do not use fermentation Reverse Electron Flow - Many are also autotrophs - need NADH and ATP to reduce CO2 - cannot donate electrons directly to NAD(P)+ a) Must use reverse electron flow Chapter 12: Anabolism: The Use of Energy in Biosynthesis Anabolism uses Energy from Catabolism - Energy from catabolism is used for biosynthetic pathways  - Macromolecules are synthesized monomers - Many enzymes do double duty - Catabolic and anabolic pathways are not identical Fixation of CO2 by Autotrophs - Many prokaryotes can grow in C compounds - CO2 fixation’s most used pathways a) Calvin-Benson (Calvin) cycle b) Reductive TCA cycle - Others cycles that we will NOT study are mostly found in the Archaea domain a) Hydroxypropionate bi-cycle b) Reductive acetyl-CoA pathway c) 3-hydroxypropionate/4-hydroxybutyrate pathway Gluconeogenesis - Functional reversal of glycolysis - the two pathways are NOT identical Assimilatory Nitrate Reduction - Used by bacteria to reduce nitrate to ammonia - Occurs in the cytoplasm of bacteria  a) Nitrate (NO3) reduction to nitrite (NO2) catalyzed by nitrate reductase b) Nitrite reduction to ammonia is catalyzed by nitrite reductase Nitrogen Fixation - Reduction of atmospheric gaseous nitrogen to NH3 - catalyzed by the enzyme nitrogenase - highly sensitive to oxygen - Only carried out by a few prokaryotes a) Chemotrophic bacteria and archaea (Klebsiella) b) Plant symbionts (Rhizobium) c) Cyanobacteria - Process in exergonic - needs 8 electrons and 16 ATP molecules - nitrogen fixing bacteria can use up to 20% of the ATP made by the host plant! Exam 4 Chapters 27 & 33: Microbial Interactions Microbial Interactions - Consortium: a host with more than one associate symbiont  a) Intermittent and cyclic b) permanent Human-Microbe Interactions - The human body is a diverse environment - super niches are present - dynamic relationships exist - Microbiome - normal micrbiota - “Superorganisms” arewhen gene encoded metabolic process of the host become integrated with those of the microbes Gut-Brain Axis - Gut microbiota may affect CNS - Specific behavioral traits: inquisitiveness, sociability, anxiety, depression - Ways the microbiome can influence the CNS: a) Microbiome effect on the immune system b) Enteric nervous system, connect to the CNS by the Vagus nerve c) Soluble microbial products (short-chain fatty acids -SCFAs) Chapter 31: Innate Host Resistance Immunity - Nonspecific immune response (Innate) - natural - first line - resistance to any microbe - lacks memory - Specific immune response (Adaptive) - acquired - resistance to a particular foreign agent  - has “memory” The Complement System - Composed of up to 30 serum proteins - Three major activities: a) Stimulating inflammatory response b) Cell lysis c) opsonization Cells of the Immune System - Leukocytes - involved in both specific and nonspecific immunity - all arise from pluripotent stem cells - Each has specialized role in defending host a) Mast cells b) Granulocytes c) Monocytes and macrophages d) Dendritic cells e) Lymphocytes Organs & Tissues of the Immune System - Primary organs and tissues - lymphocytes mature and differentiate - thymus and bone marrow - Secondary organs and tissues - lymphocytes may encounter and bind antigen - spleen, lymph nodes, MALT & SALT Toll-Like Receptors (TLRs) - Signaling receptors - Recognize and bind unique MAMPs - MyD88 dependent pathway = pro-inflammatory cytokines - TRIF-dependent pathway = interferons, chemokines and inflammatory cytokines Chapter 32: Adaptive Immunity Three major functions a) Recognize non-self b) Respond to nonself  - effector response - anamnestic response c) Remember non-self Types of Specific Immunity: Humoral vs Cellular - Humoral Immunity - antibody-mediated immunity - B cells - Cellular Immunity - cell-mediated immunity - T cells Cytotoxic T cells (Tc) - CD8+ T cells activated by antigen presented on MHC class 1 - Kill target cells via a) Perforin pathway - cytolytic pathway b) CD95 pathway - apoptotic pathway B cell Biology - Activated by a specific antigen - Differentiate into plasma cells which produce antibodies - Immunoglobulin receptors for specific antigen - B cell receptors (BCRs) - Signal transduction pathway similar to T cells Immunoglobulin Classes - IgG - 80% of serum immunoglobulin - opsonization, neutralization, activates classical complement - only Ig that can cross the placenta - has 4 subclasses - IgD - part of the B cell receptor complex - signals B cells to start antibody production - IgM - pentamer - first Ig in all immune responses - agglutination, activates classical complement - IgA, secretory IgA (sIgA)  - monomers and dimers - secreted across mucosal surfaces - tears, saliva, breast milk, MALT - has 2 subclasses - IgE - lowest Ig serum level, elevated in parasitic infection and allergic reactions - opsonization - mast cells bind Fc portion, activated to degranulate vasoactive granules Primary Antibody Response - Lag/latent period may last several days to weeks - no antibody detectable in blood - Antibody titer - IgM appears first, followed by IgG - antibody class switching Secondary Antibody Response - B cells mount a heightened, memory response - Characterized as having: a) Shorter lag b) More rapid log phase c) Longer persistence d) Higher IgG titer e) Production of antibodies with higher affinity - Basis of Vaccine Action of Antibodies - Bind antigens with great specificity - Coats foreign invading material - marks it for recognition a) Neutralization b) Opsonization c) Immune complex formation Chapter 34: Pathogenicity and Infection Pathogenicity and Infectious Disease - Host & Pathogen  - Infection & disease - Pathogenicity & virulence - Signs & symptoms VIrulence Factors: Invasiveness - Exoenzymes - Hyaluronidase - the breakdown of hyaluronic acid (HA) - bacterial spread through the tissue causes cellulitis - gram positive Staphylococcus, Streptococcus, Clostridium - some gram negative - Coagulase - fibrinogen to fibrin - coagulase positive S. aureus - Fibrinolysin - acts opposite of coagulase - plasminogen to plasmin - streptokinase is made inexpensively by Streptococci pyogenes - S. aureus has the gene on a bacteriophage and is expressed during lysogeny only - Lipase breaks down lipids - forms abscesses - Collagenase breaks down collagen - Clostridium spp. - Cell Lysis - leukocidins (pyogenic) - hemolysins - lecithinase or phospholipase - Ex: Clostridium perfringens, Staphylococcus aureus or Listeria monocytogenes Super Staphylococcus - Can produce: - B-lactamase - Catalase - Coagulase - DNase  - Enterotoxins - Exfoliative toxins A & B - Hemolysins - Hyaluronidase - Panton-Valentine leukocidin - Lipases - Nucleases - Protein A - Toxic shock syndrome toxin - 1 Exotoxins - Soluble, heat-labile, proteins - Secreted - Travel from site of infection to other tissue or cells - Usually synthesized by specific bacteria - Most producers are Gram-positive - Among the most lethal substances known - Highly immunogenic - Antitoxins vs toxoids - Diptheria toxin, Botulinum toxin, Shiga toxin, Cholera toxin, Enterotoxin, CPE, Anthrax Enterotoxins - Alter the permeability of the intestinal epithelium - Examples: a) Staphylococcus aureus - vomiting diarrhea b) VIbrio cholerae - watery diarrhea c) Shigella dysenteriae enterotoxin (Shiga toxin) and enteropathogenic E. coli (Shiga-like toxin) -AB toxins that specifically kill small intestine cells and lead to bloody diarrhea - Different ways to get enterotoxin: - Cholera, Salmonella, Shigella, and Escherichia produce enterotoxins when colonizing the intestine - Staphylococcus, Clostridia, and Bacillus cereus produce toxin in food and the toxin is ingested Secretion Systems  - T3SS (injectisome) is used by many Gram-negatives in the Enterobacteriaceae family to deliver effector proteins - virulence factor - includes Salmonella, Escherichia, Yersinia, Shigella, Enterobacter, and Citrobacter - Evolved from the flagellar apparatus - Y. pestis secretes a plasmid-encoded Yersinia outer membrane protein (YOPS) into phagocytic cells - carried by fleas - 50-100% mortality rate Endotoxin: General Features - Heat stable - Toxic in nanogram amounts - Weakly immunogenic - Generally similar, despite source - Cause general system effects - fever, weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis (the enzymatic breakdown of fibrin, the major protein component of blood clots) - Bring about these effects indirectly - interaction with macrophages leading to the release of endogenous pyrogen - binding to LPS-binding protein which leads to the release of cytokines a) Tumor necrosis (TNF) and others lead to septic shock - Lipopolysaccharide - lipid A Chapter 35: Epidemiology and Public Health Microbiology Epidemiology Terminology - Sporadic disease - Endemic disease - steady low-level frequency - common cold - Hyperendemic disease  - gradually increase - common cold in the winter - Outbreak - sudden, unexpected occurrence of disease - 2014 measles outbreak in Disneyland (CA) - Epidemic - sudden increase in frequency - index case - Pandemic - usually worldwide - H1N1 - swine flu; COVID -19 at start Herd Immunity - Level can be altered by changes in pathogen - antigenic shift vs antigenic drift Comparison of Different Vaccine Types Chapter 41: Biotechnology and Industrial Microbiology Microbes are the Source of Many Products of Industrial Importance - Industrial Products - Ethanol glucose (Saccharomyces cerevisiae) - Ethanol lactose (Kluyveromyces fragilis) - Acetone and Butanol (Clostridium acetobuylicum) - 2,3-butanediol (Enterobacter, Serratia) - Enzymes (Aspergillus, Bacillus, Mucor, Trichoderma) - Agricultural Products - Gibberelins (Gibberella fujikuroi) - Food Additives  - Amino Acids (Corynebacterium glutamicum) - Organic Acids (Aspergillus niger) - Nucleotides (Corynebacterium glutamicum) - Vitamins (Ashbya, Eremothecium, Blakeslea) - Polysaccharides (Xanthomonas) - Medical Products - Antibiotics (Penicillium, Streptomyces, Bacillus) - Alkaloids (Claviceps purpurea) - Steroid Transformations (Rhizopus, Arthrobacter) - Insulin, human growth hormone, somatostatin inferons (E. coli, Saccharomyces cerevisiae) - Biofuels - Hydrogen (Photosynthetic microorganisms) - Methane (Methanothermobacter) - Ethanol (Zymomonas, Thermoanaerobacter) Most Antibiotics are produced by Streptomyces strains and filamentous fungi - Penicillin and semisynthetic penicillin Vaccines Reverse vaccinology mines the pathogen genome sequence A “Good” antigen target is: - Expressed during infection - Secreted on the surface - Found in all strains - Elicit a host immune response - Essential for survival Biofuel Production - Ethanol - From degradation of plant starches in corn by amylases and amyloglucosidases to microbial fermentation - Hydrogen gas - Direct product of fermentation - Hydrogenase and nitrogenase enzymes - From degradation of plant starches in corn by amylases and amyloglucosidases to microbial fermentation Ideal Conditions for Growing Microbes - Knowing WHEN your microbe is producing WHAT you want is critical - Primary metabolites - include amino acids, nucleotides, fermentation end products, and enzymes - Secondary metabolites - accumulate following active growth - part of a stress response - includes antibiotics