Define Pathogen, Microbiota, Normal Flora Chapter 23 Notes

1. (pgs. 1263-1264, fig. 23-1) Define pathogen, microbiota, normal flora, microbiome, mutualism, commensalism, and parasitism. Pathogens: An organism, cell, virus, or prion that causes disease. Microbiota: The collective of microorganisms that reside in or on an organism. Normal Flora: The human microbiota consisting of approximately 1014 bacterial, fungal, and protozoan cells, representing thousands of microbial species. Microbiome: The combined genomes of the various species of a defined microbiota. Mutualism: Ecological relationship between microbes and their host in which both the microbe and host benefit. Commensalism: Ecological relationship between microbes and their host in which the microbe benefits but offers no benefit and causes no harm. Parasitism: Ecological relationship between microbes and their host in which the microbe benefits to the detriment of the host, as is often the case for pathogens. 2. (pgs.1264-1265) Define primary and opportunistic pathogen. List the four categories in which a pathogen must be able to do to be successful. Primary Pathogens: Pathogens that can 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 without causing overt disease, the host often being unaware that they are infected. Opportunistic Pathogens: Microbes of the normal flora that can cause disease only if the immune systems are weakened or it they gain access to a normally sterile part of the body. In order to survive and multiply, a successful pathogen must be able to : 1) Enter the host (usually by breaking an epithelial barrier) 2) Find a nutritionally compatible niche in the host’s body 3) Avoid, subvert, or circumvent the host’s innate and adaptive immune responses 4) Replicate, using host resources 5) Exit one host and spread to another 3. (pgs. 1255-1256) Briefly describe the examples of cancer-causing pathogens. Some viral and bacterial pathogens can cause or contribute to chronic, life-threatening illnesses that are not normally classified as infectious diseases. Rous sarcoma virus – causes a form of cancer (sarcomas) in chickens Human papillomavirus – causes genital warts, is responsible for more than 90% of cervical cancers H. pylori – major contributor to stomach cancer Atherosclerosis – the accumulation in blood vessel walls of fatty deposits that can block blood flow and cause heart attacks and strokes. Chlamydia pneumoniae – commonly causes pneumonia in humans and is a significant risk factor for atherosclerosis in humans and animal models 4. (pgs. 1267-1268, figs. 23-3 and 23-4) 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 Staining: A technique for classifying bacteria based on differences in the structure of the bacterial cell wall and outer surface. Gram Positive: Description for bacteria that stain positive with gram stain die to a thick layer of peptidoglycan cell wall outside their inner (plasma) membrane. Gram Negative: Description for bacteria that do not stain with Gram stain as a result of having a thinner peptidoglycan cell wall outside their inner (plasma) membrane, and on an additional outer membrane. Gram negative bacteria are also covered outside the cell wall by an outer membrane containing lipopolysaccharide (LPS). Both peptidoglycan and LPS are unique to bacteria and are recognized as pathogen-associated molecular patterns (PAMPs). The inner leaflet of the outer membrane of gram-negative bacteria is also made primarily of phospholipids, whereas the outer leaflet of the outer membrane is composed of a unique glycosylated lipid called lipopolysaccharide (LPS). Facultative Pathogens: Bacteria that replicate in an environmental reservoir such as water or soil and only cause disease if they happen to encounter a susceptible host. Obligate Pathogens: Bacteria that can only replicate inside their host. Virulence Gene: Gene that contributes to an organism’s ability to cause disease. Virulence Factors: Proteins, encoded by a virulence gene, that contributes to an organism’s ability to cause disease. 5. (pgs. 1268-1269, fig. 23-5) Describe horizontal gene transfer and its three mechanisms. To what degree do we see genomic variation within the same species? Understand figure 23-5. Horizontal Gene Transfer: Gene transfer between bacteria via natural transformation by released naked DNA, transduction by bacteriophages, or sexual exchange by conjugation. Sequencing the genomes of large numbers of pathogenic and nonpathogenic bacteria has indicated that horizontal gene transfer has made important contribution to bacterial evolution, enabling species to inhabit new ecological and nutritional niches, as well as to cause disease. Even within a single bacterial species, the amount of chromosomal variation is astonishing; the genomes of different strains of E. coli can differ by as much as 25%. Such variation has led to the concept that a bacterial species has both a core genome common to all isolates within the species and a larger pangenome consisting of all genes present in the full spectrum of isolates. 6. (pgs. 1269-12-71, 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 Vibrio cholerae responsible for causing the watery diarrhea associated with cholera. Comprises an A subunit with enzymatic activity and a B subunit that binds to hot-cell receptors to direct subunit A to the host cell cytosol. The A subunit catalyzes the transfer of an ADP-ribose moiety from NAD+ to the trimeric G protein Gs, which activates adenylyl cyclase to make cyclic AMP. ADP-ribosylation prevents inactivation of the G protein and results in the overaccumulation of intracellular cyclic AMP and the release of ions and water into the intestinal lumen, leading to the watery diarrhea associated with cholera. The infection then spreads to new hosts via released bacteria, which can contaminate food and water. Some pathogenic bacteria secrete multiple toxins, each of which targets a different signaling pathway in host cells. Anthrax, for example, is an acute infectious disease of sheep, cattle, and occasionally humans. It is caused by contact with spores of the Gram-positive bacterium Bacillus anthracis. Dormant spores can survive in soil for long periods. If inhaled, ingested, or rubbed into breaks in the skin, spores can germinate and the bacteria replicate. The bacteria secrete two toxins with identical B subunits but different A subunits. The B subunits bind to a host cellsurface receptor protein to transfer the two different A subunits into host cells. Secretion Systems: Specialized bacterial systems that secrete effector proteins that interact with host cells. 7. (pgs. 1271-1273, figs. 23-8 and 23-9) Describe the phenomena of dimorphism of pathogenic fungi. Describe the lifecycle of malaria parasites. Most important pathogenic fungi exhibit dimorphism – the ability to grow in either yeast or mold form. The yeast-to-mold or mod-to-yeast transition is frequently associated with infection. Histoplasma capsulatum, for example, grows as a mold at low temperatures in the soil, but it switches to a yeast form when inhaled into the lung, where it can cause the disease histoplasmosis. Malaria: Protozoal disease caused by four species of Plasmodium, which are transmitted to humans by the bite of the female Anopheles mosquito. Plasmodium falciparum causes the most serious form of malaria-causing parasites. It exists in many distinct forms, and it requires both the human and mosquito hosts to complete its sexual cycle. 8. (pgs. 1273-1275, 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. Viral replication involves: 1) Entry into the host cell 2) Disassembly of the infectious virus particle 3) Replication of the viral genome 4) transcription of viral genes and synthesis of viral proteins 5) assembly of these genes and synthesis of viral proteins 6) release of progeny virions Viral genomes are packaged in a protein coat, called a capsid, which in some viruses is further enclosed by a lipid bilayer membrane, or envelope. For enveloped viruses, the nucleocapsid is enclosed within a lipid bilayer membrane that the virus acquires in the process of budding from the host-cell plasma membrane, which it does without disrupting the membrane or killing the cell. Enveloped viruses can cause persistent infections that may last for years, often without noticeable deleterious effects on the host. 9. (pgs. 1277-1278, fig. 23-16) Describe the mechanism for how Bordetella pertussis causes an infection. Describe the mechanism for how EPEC causes an infection. Bordetella pertussis, the bacterium that causes whooping cough, colonizes the respiratory epithelium and circumvents the normal mechanism that clears the respiratory tract by expressing adhesins that bind ciliated epithelial cells. The adherent bacteria produce toxins that eventually kill the ciliated cells, compromising the host’s ability to clear the infection. Enteropathogenic E. coli (EPEC), which causes diarrhea in young children, uses a type III secretions system to deliver its own special receptor protein (called Tri) into the plasma membrane of a host intestinal epithelial cell. The extracellular domain of Tir binds to the bacterial surface protein intimin, triggering actin polymerization in the host cell that results in the formation of a unique cell-surface protrusion called a pedestal; this pushes the tightly adherent bacteria up about 10 um from the host-cell membrane, thereby promoting bacterial movement along the cell surface. 10. (pgs. 1281-1282, fig. 23-19) 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-1, which requires two types of receptors to enter a host cell. Its primary receptor is CD4, a cell-surface protein on helper T cells and macrophages that is involved in immune recognition. It also requires a co-receptor, which is either CCR5 (a receptor for β-chemokines) or CXCR4 (a receptor for α-chemokines), depending on the particular variant of the virus; macrophages are susceptible only to HIV variants that use CCR5 for entry, whereas helper T cells are most efficiently infected by variants that use CXCR4. The viruses that are found within the first few months after HIV infection almost invariably use CCR5, which explains why individuals that carry a defective CCR5 gene are less susceptible to HIV infection. Four virus entry strategies: 1) Some enveloped viruses, such as HIV, fuse directly with the host-cell plasma membrane to release their RNA genome (blue) and capsid proteins (brown) into the cytosol. 2) Other enveloped viruses, such as influenza virus, first bind to cell-surface receptors, triggering receptor-mediated endocytosis; when the endosome acidifies, the virus envelope fuses with the endosomal membrane, releasing the viral RNA genome (blue) and capsid proteins (brown) into the cytosol. 3) Poliovirus, a nonenveloped virus, induces receptor-mediated endocytosis, and then forms a pore in the endosomal membrane to extrude its RNA genome (blue) into the cytosol. 4) Adenovirus, another nonenveloped virus, uses a more complicated strategy: it induces receptor-mediated endocytosis and then disrupts the endosomal membrane, releasing the capsid and its DNA genome into the cytosol; the trimmeddown virus eventually docks onto a nuclear pore and releases its DNA (red) directly into the nucleus. Some bacterial pathogens can invade host cells that are normally nonphagocytic. Actin polymerization, together with the assembly of a clathrin coat, drives the advancement of the host cell’s plasma membrane over the adhesive surface of the microbe, resulting in the phagocytosis of the bacterium – a process known as the zipper mechanism of invasion. A second pathway by which bacteria can invade nonphagocytic cells is known as the trigger mechanism. It is used by various pathogens that cause food poisoning, and is initiated when the bacterium injects a set of effector molecules in the host-cell cytosol through a type III secretion system. 11. (pgs. 1282-1283, figs. 23-20 and 23-21) Describe how the eukaryotes T. gondii and T. cruzi (two methods) gain entry to their host cells. Toxoplasma gondii, a cat parasite that also causes occasional serious human infections, is an example. When this protozoan contacts a host cell, it protrudes an unusual microtubule-based structure called a conoid, which facilitates entry into the host cell. At the point of contact, the parasite discharges effector proteins from secretory organelles into the host cell, and these proteins target various host pathways to enable invasion, to block an innate immune response, and promote survival. As the parasite moves into the host cell, a membrane derived from the host-cell plasma membrane surrounds it. Remarkably, the parasite removes host transmembrane proteins from the surrounding membrane as it forms, so that the parasite is protected in a membrane-enclosed compartment that does not fuse with lysosomes and does not participate in hostcell membrane trafficking processes. The specialized membrane is selectively porous: it allows the parasite to take up small metabolic intermediates and nutrients from the host cell’s cytosol but excludes macromolecules. The protozoan Trypanosoma cruzi, which causes Chagas disease in Mexico and Central and South America, uses two alternative invasion strategies. In a lysozymedependent pathway, the parasite attaches to host cell-surface receptors, including a local increase in Ca2+ in the host cell’s cytosol. The Ca2+ signal recruits lysosomes to the site of parasite attachment, and the lysosomes fuse with the host cell’s plasma membrane, allowing the parasites rapid access to the lysosomal compartment. In a lysosomeindependent pathway, the parasite penetrates the host-cell plasma membrane by inducing the membrane to invaginate, without the recruitment of lysosomes. 12. (pgs. 1286-1289, figs. 23-28 and 23-29) Describe the pathogen strategy for actin-based movement in the host’s cytoplasm. Describe the mechanisms that bacteria employ for actin nucleation. Be familiar with the various ways that viruses use their host’s DNA and RNA replication machinery. Viruses use basic host cell machinery for most aspects of their reproduction: they depend on host-cell ribosomes to produce their proteins, and most use host-cell DNA and RNA polymerases for their own replication and transcription. Many viruses encode proteins that modify the host transcription or translation apparatus to favor the synthesis of viral RNAs and proteins over those of the host cell, shifting the synthetic capacity of the cell toward the production of new virus particles. Viruses also alter translation by the host. Translation initiation for most host-cell mRNAs depends on recognition of their 5ʹ cap by translation initiation factors. This initiation process is often inhibited during viral infection, so that the host-cell ribosomes can be used more efficiently for the synthesis of viral proteins. RNA viruses mist always encode their own replication protein because host cells lack polymerase enzymes that use RNA as a template. For RNA viruses with a single-stranded genome, the replication strategy depends on whether the RNA is positive strand, which contains translatable information like mRNA, or a complementary negative strand. 13. (pgs. 1291-1292, figs. 23-31 and 23-32) 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. Viruses rely on an error-prone replication mechanism for antigenic variation. Retroviral genomes, acquire an average of one point mutation every replication cycle, because the