BIO 333 Chapter 23 Guide (Week 13) PDF

Name_Isabel Hernandez Carrillo_ BIO-333 Chapter 23 Guide 7e 1. (pgs. 1313-1315, fig. 23-1 and 23-2) Define pathogen and microbiota.  Pathogen- An organism, cell, virus, or prion that causes disease. o Exploit the attributes of their host’s cells in order to infect them. ...

Name_Isabel Hernandez Carrillo_ BIO-333 Chapter 23 Guide 7e 1. (pgs. 1313-1315, fig. 23-1 and 23-2) Define pathogen and microbiota.  Pathogen- An organism, cell, virus, or prion that causes disease. o Exploit the attributes of their host’s cells in order to infect them.  Microbiota- Collective of microorganisms that resides in or on an organism. 2. (pgs. 1314-1315) Define primary and opportunistic pathogen. List the four categories in which a pathogen must be able to do to be successful.  Primary pathogen- Cause overt disease in most healthy people. Some cause acute, life- threatening epidemic infections and spread rapidly between hosts; other potential primary pathogens may persistently infect a single individual for years w/out causing overt disease, the host often being unaware of being infected.  Opportunistic pathogen- Microbes of normal flora that can cause disease only if the immune systems are weakened/if they gain access to a normally sterile part of the body.  Four categories in which a pathogen must be able to do to be successful: o Enter the host (break epithelial barrier) o Find a nutritionally compatible niche in the host’s body o Avoid subvert/circumvent the host’s innate and adaptive immune responses o Replicate using host resources and exit ones host and spread to another 3. (pgs. 1315-1317, fig. 23-3) Describe Gram-positive and Gram-negative bacteria. What are LPS and PAMPs. Define facultative and obligate pathogens. What are virulence genes and virulence factors?  Gram (+): Bacteria that stain positive with Gram stain because of a thick layer of peptidoglycan cell wall outside their inner (plasma) membrane.  Gram (-): Bacteria doesn’t stain w/Gram stain as a result of having a thin peptidoglycan cell wall outside their inner (plasma) membrane that is covered by a second lipid- containing outer membrane. o Lipopolysaccharide (LPS)- Outer membrane covering the cell wall of a Gram (-) bacteria. o Pathogen-associated molecular patterns (PAMPs)- Molecular structures/molecules that are shared by most pathogenic bacteria and some viruses.  Include peptidoglycan and LPS  Recognized by host immune system  Both Gram (+) and (-) help protect the cell wall against lysis by osmotic swelling and it is the target of antibacterial proteins (lysozyme) and antibiotics (penicillin).  Facultative pathogens- Bacteria that replicate in an environmental reservoir such as water/soil and only cause disease if they happen to encounter a susceptible host.  Obligate pathogens- Bacteria that can only replicate inside the host.  Virulence genes- Contributes to an organism’s ability to cause disease.  o Virulence factors- Protein, encoded by virulence gene, that contributes to an organism’s ability to cause disease. o They often cluster together on the bacterial chromosome large clusters= pathogenicity islands Figure 23-3: Bacterial shapes and cell-surface structures. 4. (pgs. 1317-1319, figs. 23-4 and 23-5) Understand figure 23-5. Describe horizontal gene transfer and its three mechanisms. To what degree do we see genomic variation within the same species?  Horizontal gene transfer: Gene transfer between bacteria/archaea via.. o 3 mechanisms:  Natural transformation by released naked DNA  Transduction (infection) by bacteriophages  Sexual exchange by conjugation  Ex: In E. coli a genomic variation of 25% can be seen  Led to concept bacterial species have a core genome (common to all isolates w/in species) and larger pangenome (all genes present in full spectrum of isolates).  Figure 23-5: A V. cholerae (Gram neg.) bacterium strand cause a pandemic human disease to those infected with a mobile bacteriophage (CTX) that encodes two subunits of toxins that causes diarrhea. First six pandemics were caused by periodic reemergence of classical strains. Similar to O1 surface antigen that is part of the LPS. The seventh pandemic was caused by a strain named El Tor (wave 1) that arose when O1-expressing strain acquired CTX-1 and RS1 bacteriophages and @ least 2 new pathogenicity islands. More strains emerged as seen in figure. Figure 23-24: Genetic differences between pathogenic and nonpathogenic bacteria. Figure 23-25: Model for evolution of pathogenic V. cholerae strains.  5. (pgs. 1319-1321, figs. 23-6 and 23-7) Describe the mechanisms for how anthrax and cholera toxins enter host cells. What are secretion systems?  Cholera toxin: Secreted toxic protein of V. cholerae responsible for causing water diarrhea associated w/cholera. Comprises an A subunit w/enzymatic activity and a B subunit that binds to the host-cell receptors to direct subunit A to the host-cell cytosol. o The A subunit catalyzes transfer of ADP-ribose moiety from NAD+ to the trimeric G protein Gs. The ADP ribosylation alters the G-protein A subunit so that it can no longer hydrolyze its bound GTP causing it to remain in an active state stimulating adenylyl cyclase indifferently. Result of prolonged elevation of cAMP concentration w/in intestinal epithelial cells causing a large efflux of Cl- and water into the gutdiarrhea  Anthrax: Acute infectious disease of sheep, cattle, and occasionally humans. Cause by contract w/spores of Gram (+) bacterium. Spore can germinate and bacteria replications occurs when spores are ingested, inhaled, or rubbed into breaks in the skin. o Two toxins with identical B subunits but different A subunits  B subunit binds to a host-cell surface receptor protein to transfer two different A subunits into host cells.  A subunits:  Lethal factor- Protease that cleaves several activated members of the MAP kinase kinase family and causes a large fall in bp and death on entry into the bloodstream of an animal.  Edema factor- An adenylyl cyclase that catalyzes production of cAMP, leading to ion imbalance and consequent edema in the skin/lung.  Secretion systems- Secrete effector proteins directly into host cell targets. o Two present in Gran (-) bacteria:  Type III secretion- Delivers effectors proteins into host cells in a contact- dependent manner.  Extracellular pathogen= enables bacterium to block phagocytosis by immune cells  Intracellular pathogen= promote phagocytosis by nonimmune cells/survival inside cells.  Type IV secretion- Related to conjugation apparatus that bacteria use to exchange genetic material Figure 23-7: Contact- dependent type III secretion systems can deliver effector proteins from the cytosol of a bacterium directly into the host cell. Figure 23-6: Toxins released by bacteria. 6. (pgs. 1321-1322, figs. 23-8 and 23-9) Describe the phenomena of dimorphism of pathogenic fungi. Describe the lifecycle of malaria parasites.  Dimorphism- Ability to grow in either yeast/mold form o Associated with infection  Protozoan parasites- Nonphotosyntheic, single-celled, motile eukaryotic organism.  Malaria: Protozoal disease cause by 1 of 4 species of Plasmodium, which are transmitted to humans by the bite of the female Anopheles mosquito. o Lifecyle of malaria parasites seen in figure 28-9: Figure 23-8: Dimorphism in pathogenic fungus. Figure 23-9 continued. Figure 23-9 7. (pgs. 1322-1325, figs. 23-10, 23-11, 23-12, and 23-13, Table 23-1) Describe the six general categories that viruses rely on to be successful. Be aware of the different viral morphologies. Describe how a virus acquires an envelope. Understand figure 23-13.  Six categories that viruses rely on to be successful: o Entry to host cell o Disassembly of the infectious virus particle o Replication of the viral genome o Transcription of viral genes and synthesis of viral proteins o Assembly of viral components into progeny virus particles o Release of progeny virions  Single virion that infects a single host cell can produce thousands of progeny.  Viral genomes packed in a capsid than is enclosed in an envelope. The capsid packaged w/viral genome (nucleocapsid) is enclosed by a lipid bilayer membrane that the virus acquires in the process of budding from the host-cell plasma membrane w/out disrupting the membrane/killing the cell.  o Capsid- Protein coat of a virus, formed by self-assembly of one or more types of protein subunit into a geometrically regular structure.  Figure 23-13:  vaccinations/immunization =  disease incidence Figure 23-12: Acquisition of a vial envelope. Figure 23-10: Viral life cycle Figure 23-11: Morphology of viral members. 8. (pgs. 1325-1328, figs. 23-14, 23-15, and 23-16) Generally describe how some pathogens enter their host. Describe the entry strategy for Yersinia pestis. How does H. pylori persist in the stomachs of its host and how was this bacterium identified as the cause of stomach ulcers?  Pathogenic entry to their host: Wounds in barrier epithelia allows direct access to unoccupied niches (requires little specialization). Another way is to enter along with saliva of a biting arthropod. Vectors used for transmission. Vectors requires that an individual insect consumes a blood meal from an infected host and transfers the pathogen to a nonimmune host.  Yersinia pestis: Multiplies in the flea’s foregut to form aggregated masses that physically block the digestive tract. During each attempt at feeding some of the bacteria in the foregut are flushed into the bite site thus transmitting plague to a new host. o Yersinia pestis= Bubonic plague  H. pylori: Persists for life as part of the stomach microbiota. Doesn’t cause disease in most individuals but can cause stomach ulcers and caners. Several adaptations that allow it to colonize the harsh environment: 1)Uses its flagella for chemotactic motility allowing it to penetrate mucus and seek out more neutral pH near the surface of gastric epithelial cells. 2) Produces urease that converts urea to ammonia to neutralize the acid in its immediate vicinity. o ID to cause stomach ulcers because an Australian doc drank pure culture of bacteria and developed inflammation of the stomach and therefore developed ulcers. Figure 23-15: Pathogenic E. coli in the infected bladder of a mouse. Figure 23-16: H. pylori interaction w/epithelial cells in the stomach lining. 9. (pgs. 1328-1329, fig. 23-17) Describe the mechanism for how Bordetella pertussis causes an infection. Describe the mechanism for how EPEC causes an infection.  Extracellular pathogens- Disturb host cells and can cause serious disease without replicating in host cells.  Bordetella pertussis: Colonizes the respiratory epithelium and circumvents normal mechanism that clears respiratory tract by expressing adhesins that blind ciliated epithelial cells. Adherent bacteria produce a toxins that will eventually kill the ciliated cells, compromising the host’s ability to clear the infection.  o Pertussis toxin: Has an A subunit that ADP-ribosylates the alpha subunit of the G protein Gi, causing G protein to remain in the inactive GDP-bound state and preventing it from inhibiting activity of host cell’s adenylyl cyclase. It increases the production of cyclic AMP. It can also interfere w/chemotactic pathway that neutrophils use to seek out and destroy bacteria. o Bordetella pertussis= Whooping cough  Enteropathogenic E. coli (EPEC): Uses a type III secretion system to deliver its own special receptor protein (Tri) into the plasma membrane of a host intestinal epithelial cell. The extracellular domain of Tri binds to the bacterial surface protein (intimin) triggering actin polymerization in host cell. This results in formation of unique cell- surface protrusion (pedestal). The pedestal pushes the tightly adherent bacteria from the host-cell membrane promoting bacterial movement along the cell surface by a mechanism for actin-based motility of intracellular pathogens. o It causes diarrhea and can be lethal to young children. Figure 23-17: Interaction of EPEC w/host intestinal epithelial cells. 10. (pgs. 1329-1333, figs. 23-18, 23-19, and 23-20) Describe the mechanisms for HIV infection. Who might be immune to this virus? Describe the four viral entry strategies. Describe the zipper and trigger mechanisms.  HIV infection: Primary receptor CD4 a cell-surface protein on helper T cells and macrophages that is involved in immune recognition. CD4 uses a co-receptor that is either CCR5 (receptor for B-chemokines) or CXCR4 (receptor for a-chemokines). In early stages HIV invariably use CCR5 and in later stages of infection viruses switch to use CXCR4 or adapt to use both co-receptors through accumulation of viral mutations. o Macrophages are only susceptible to HIV variants that use CCR5 for entry o Helper T cells most efficiently infected by variants that use CXCR4 o Immunity?= Individuals with an altered CCR5 gene Figure 23-18: Receptor and co-receptors for HIV.  4 viral entry strategies: o Fusion w/plasma membrane release their RNA genome and capsid proteins into the cytosol  Ex: HIV o Fusion w/membrane after endocytosis when endosome acidifies the virus envelope fuses w/endosomal membrane releasing viral RNA genome and capsid proteins into cytosol  Ex: Influenza virus o Pore formation  Ex: Poliovirus o Endosomal membrane disruption it then disrupts the endosomal membrane releasing capsid including its DNA genome into the cytosol  Ex: Adenovirus  Zipper mechanism- Bacteria express an invasion protein that binds w/high affinity to a host-cell receptor  Trigger mechanism-Bacterium injects a set of effector molecules into the host-cell cytosol through a type III secretion system.  Zipper and trigger mechanisms cause polymerization of actin at the site of bacterial attachment by activating Rho family small GTPases and Arp2/3 complex. Figure 23-20: Mechanisms used by bacteria to induce phagocytosis by host cells that are normally nonphagocytic. 11. (pgs. 1333-1334, figs. 23-21 and 23-22) Describe how the eukaryotes T. gondii and T. cruzi (two methods) gain entry to their host cells.  T. gondii: Protrudes a microtubule-based structure called a conoid that facilitates host- entry. At the point of contact the parasite discharges effector proteins into the host cell from specialized secretory organelles. One effector inserts into the host-cell plasma membrane and binds to a parasite surface protein. The other effector forms a ring-like moving junction in which the parasite squeezes using forces generated by its own unusual actin and myosin cytoskeleton. Parasite invades removing host transmembrane proteins from surrounding membrane so that it eventually protected in a membrane- enclosed compartment (parasitophorous vacuole) that doesn’t fuse w/lysosomes and doesn’t participate in host-cell membrane trafficking processes. o Membrane is selectively porous allowing it to take up small metabolic intermediate and nutrients from host but excluding macromolecules. o Cat parasite that cause infection in pregnant and immunocompromised individuals.  T. cruzi: Causes Chagas disease o Lysosome-dependent pathway- Parasite attaches to the host’s cell-surface receptors including a local increase in Ca2+ in the host cell’s cytosol. Ca2+ signal recruits lysosomes to site of parasite attachment and then lysosome fuses w/host cell’s plasma membrane. Allows for rapid access to lysosomal compartment. o Lysosome-independent pathway- Parasite penetrates host-cell plasma membrane by inducing the membrane to invaginate w/out lysosome recruitment. Figure 23-21: Life cycle of intracellular parasite T. gondii.  Figure 23-22: Two alternative strategies that T. cruzi uses to invade host cells. 12. (pgs. 1334-1335, figs. 23-23 and 23-24) Describe the general strategies that intracellular pathogens employ to escape the effects of a lysosome? Describe how L. monocytogenes escapes the phagosome.  Escaping effects of lysosome: o Some escape endosomal compartment before fusion o Others remain in the endosome compartment but modify it to no longer fuse w/lysosome o Finally, others evolve to weather the harsh conditions in the lysosomes.  L. monocytogenes: After phagocytosis by the zipper mechanism, it secretes listeriolysin O that helps disrupt the phagosomal membrane releasing the bacteria into the cytosol (must be in a low pH). Once inside it begins to replicate and continues to secrete listeriolysin O. Until the pH is above 6 making it less active. It is then rapidly degraded by proteasomes. Figure 23-23: Choices that intracellular pathogen faces Figure 23-24: Escape of listeria monoctogenes by selective destruction of phagosomal membrane. 13. (pgs. 1335-1338, figs. 23-25, 23-26, 23-27, and 23-28) Describe how M. tuberculosis, S. enterica, and L. pneumophila evade the phagosome. Describe the strategies for viral envelope acquisition.  M. tuberculosis: Prevents maturation of early endosome that contains the bacteria so the endosome never acidifies/acquires other characteristics of a late endosome/lysosome.  S. enterica: Acidify and acquire markers of late endosomes and lysosomes but the bacteria slow the process of phagosome maturation. This is done by injecting effector proteins through a second type III secretion system, distinct from that involved in invasion by the trigger mechanism. Some bacterial effectors activate host kinesin motor proteins to pull membrane tubules outward from the phagosome along cytoplasmic microtubules, forming a specialized compartment called Salmonella-containing vacuole.  L. pneumophila: Use a type IV secretion systems to inject effector proteins into the phagocyte that modulate the accumulation of phosphoinositides and the activity of proteins that regulate vesicular traffic including SNARE proteins and Rab and Arf family small GTPase. Effectors prevent phagosomes from fusing w/endosomes that promote its fusion w/ER, converting the phagosome into a compartment that resembles the rough ER.  Strategies for viral envelope acquisition through budding from the cell membrane (plasma membrane, ER, Golgi, or nuclear membrane). Figure 23-25: Modifications of membrane traffic in host cells by Figure 23-26: Salmonella enterica residing in a bacterial pathogens to slow/prevent normal fusing of endosome modified phagosomal compartment called w/lysosomes. Salmonella-containing vacuole. Figure 23-27: Legionella pneumophila residing in a compartment w/characteristics similar to those of the rough ER. Figure 23-28: Complex strategies for viral envelope acquisition. 14. (pgs. 1338-1339, figs. 23-29, 23-30, and 23-31) Describe the pathogen strategy for actin- based movement in the host’s cytoplasm. Describe the mechanisms that bacteria employ for actin nucleation. Describe microtubule-based movement of viruses.  Pathogens induce nucleation and assembly of host-cell actin filaments @ one pole of the microbe. Growing filaments generate force and push the pathogens through the cytosol at rates of up to 1 um/min. New filaments form @ the rear of each pathogen and are left behind like a rocket tail as microbe advances. Moving bacteria collide w/membrane and move outward inducing formation of long, thin, host-cell protrusions w/bacteria @ their tip. Neighboring cells engulf projections allowing bacteria to enter neighbor’s cytoplasm w/out exposure to extracellular environment.  Secrete effector proteins that mimic/directly interact w/host cell actin nucleators such as Arp2/3 complex/formins. Effectively hijacking host cell machinery to polymerize actin filaments for their own movement w/in cell.  Enter sensory neurons @ tips of their axon and move by retrograde (backward) axonal transport along the axon toward the microtubule minus end. Transport mediated by attachment of viral capsid protein to motor protein dynein. Viruses then establish productive/latent infection in nuclei of neurons of PNS. After they are carried by anterograde (forward) axonal transport along microtubules to axon tips w/transport mediated by attachment of different viral capsid protein to a kinesin motor protein. o Others associate w/either dynein/kinesin motor proteins to move along microtubules @ some stage of replication. o Some alter dynamic assembly and disassembly of microtubules.  Figure 23-30: Molecular mechanisms for actin nucleation by various bacterial. pathogens. Figure 23-29: Actin-based movement Figure 23-31: Microtubule-based movement of viruses. of bacterial pathogens w/in and between host cells. 15. (pgs. 1340-1341, fig. 23-32) Describe the mechanisms for how microbes manipulate autophagy. Be familiar with the various ways that viruses use their host’s DNA and RNA replication machinery.  Manipulation of autophagy: o Deploy a protective shield that prevents detection of microbe by host cells o Secrete bacterial enzymes and harness actin-based movement to avoid enclosure of autophagosomes. o Replication inside a membrane-bound compartment that recruits and fuses w/autophagosomes to deliver nutrients as well as lipid for other compartment expansion.  Promotes virus trafficking  Ways viruses use their host’s DNA and RNA: o Encode proteins that modify host transcription/translation apparatus to favor synthesis of viral RNAs and proteins over those of the host cell shifting to synthetic capacity of cell toward production of new virus particles. o Initiation process inhibited so host cell ribosomes can be used more effectively for synthesis of viral proteins. Some encode endonucleases that cleave off 5’ cap from host-cell mRNAs.  Initiation= Recognition of 5’cap by translation initiation factors  Figure 23-32: Microbial manipulation of autophagy. 16. (pgs. 1340-1343, fig. 23-33) What are two main advantages that pathogens have that enable them to evolve rapidly? Describe the purpose and function of antigenic variation in trypanosomes.  Two main advantages: o Replicate quicky providing great deal of mutational variation for natural selection to work with. o Selective pressures act rapidly on genetic variation. Host’s adaptive immune system and modern microbial drugs both which destroy pathogens fail to change= main sources of selective pressures.  Antigenic variation in trypanosomes: o Antigenic variation- Ability to change antigens displayed on cell surface. o T. brucei is covered by single multi variant glycoprotein (VSG) that express one Vsg gene at any one time. Thereby altered trypanosomes w/altered VSG escape initial antibody-mediated clearance, replicate, and cause disease to recur leading to chronic cyclic infection.  20 possible expression sites Figure 23-33: Antigenic variation in trypanosomes 17. (pgs. 1343-1344, figs. 23-34 and 23-35) Why is DNA/RNA replication so error prone among viruses? How does this speed up their evolution? Describe the evolution of pandemic strains of the influenza virus.  Retroviral genomes (RNA genome) lacks proofreading activity of DNA polymerases. Therefore, leads to high mutation rates that speed up their evolution by providing constant stream of genetic variation for natural selection to act upon.  Influenza virus: o (Spanish flu) 1918: Virulent form of the virus crosses species barrier from birds to humans  H1N1 (hemagglutinin and neuraminidase) o (Asian flu) 1957: New pandemic when 3 genes replaced by equivalent genes from different avian virus. New strains wasn’t effectively cleared by antibodies in ppl who had previously contracted only H1N1 forms of influenza.  H2N2 o (Hong Kong flu) 1968: Two genes replaced from yet another avian virus  H3N2 o (Russian flu) 1977: Resurgence of H1N1 influenza that had previously been almost completely replaced by N2 strains.  Might have been due to accidental release of lab strains or by vaccine study o 2009: New H1N1 swine virus emerged that had derived 5 genes from pig influenza viruses, two from avian, and one from human influenza. o Most human influenza today is caused by H1N1 and H3N2 strains. Figure 23-35: Model of evolution of pandemic strains of influenza virus by recombination. 18. (pgs. 1344-1346, figs. 23-36 and 23-37) List the antibiotic targets that display selective toxicity. Describe the three general mechanisms of antibiotic resistance.  Target bacterial enzymes that either are distinct from their eukaryotic compartments/involved in pathways such as cell-wall biosynthesis that are absent in animals. o Targets: Cell membrane, DNA gyrase, RNA polymerase, Protein synthesis (30S and 50S ribosome inhibitors), Folic acid biosynthesis, and Cell-wall synthesis.  Three general mechanisms of antibiotic resistance:  o Alter molecular target of drug so that it is no longer sensitive to the drug o Produce an enzyme that modifies/destroys the drug o Prevent drug’s access to drug target by…(ex: pumping drug out of pathogen). Figure 23-36: Antibiotic targets. Figure 23-37: 3 General mechanisms of antibiotic resistance. 19. (pgs. 1347-1349, figs. 23-38 and 23-39) Define pathogen, microbiota, normal flora, microbiome, mutualism, commensalism, and parasitism. What are some of the benefits humans receive from their microbiome?  Pathogen- Agents that are capable of causing infectious disease.  Microbiota- Collective of microorganisms that reside in/on an organism.  Normal flora- Non-disease-causing microbiota of an organism.  Microbiome- Combined genomes of various species of a defined microbiota.  Mutualism- Ecologic relationship between microbes and their host in which both microbe and host benefit.  Commensalism- Ecologic relationship between microbes and their host in which the microbe benefits but offers no benefit and causes no harm.  Parasitism- Ecologic relationship between microbes and their host in which the microbe benefits to the detriment of the host, as is often the case for pathogens.  Benefits humans receive from their microbiome: Assistance w/digestion, protection against harmful bacteria, immune system regulation, and production of essential nutrients (ex: vitamins) Figure 23-38: Sites in human body that harbor the microbiota Include skin, mouth, and digestive tract. Figure 23-39: Influence of microbiota on metabolism and development.