MCDB 1030 – Spring 2005 Homework Set 4 Bacterial and Viral Infections 1. How is anthrax normally spread among herbivores? How can humans acquire the disease? Herbivores acquire anthrax by ingesting the spores. The spores germinate in side the animal and reproduce. Eventually the toxins will kill the animal and the bacteria will sporulate when they are released into the environment. Humans can acquire the diseases in three ways: 1) ingestion 2) cutaneous exposure (through an abrasion in the skin) 3) inhalation 2. Why is inhalational anthrax usually fatal even if antibiotics are given? Inhalational anthrax is usually fatal because, by the time serious symptoms appear, enough toxin has been released to cause death. Antibiotics will kill the bacteria, but will not prevent the action of the toxin. 3. What is the role of protective antigen in anthrax? Protective antigen shuttles lethal factor and edema factor across the membrane of host cells and then across the membrane of the vesicle into the cytoplasm. 4. What are the three forms of plague caused by Yersinia pestis? How is each spread? a) bubonic plague – (localized to lymph nodes) - spread by bite of infected flea b) septicemic plague – (bacteria in blood stream) – spread by bite of infected flea c) pneumonic plague – spread by coughing 5. What is a Type III secretion system? How does it contribute to virulence? A Type III secretion system is a protein complex that allows proteins to be injected from a bacterium through the membrane of a host cell. It contributes to virulence by manipulating the behavior of the host cell. For example, Y. pestis injects proteins into macrophages that impair their ability to respond to an infection by interfering with the shape change required for phagocytosis and causing the macrophages to under go apoptosis. 6. List 4 major targets for antibiotics. Four of the following: d) inhibition of cell wall synthesis e) inhibition of translation f) disruption of the cytoplasmic membrane g) inhibition of metabolic pathways h) inhibition of nucleic acid synthesis not such a good answer: prevention of attachment (this is mostly relevant for viruses; note that the term antibiotics is usually to refer to drugs for treatment of bacterial infections) 7. List 4 strategies by which bacteria can become resistant to antibiotics. Four of the following: i) j) k) l) e) modification or destruction of antibiotic by enzymes pumping antibiotic out of the cell alteration of the target by mutations that change its shape prevent antibiotic from getting into the cell develop an alternative metabolic pathway to get around the blocked step 8. Describe the role of each of the following in HIV infection. a) reverse transcriptase – copies the single stranded RNA strands into single stranded DNA, then copies the DNA to give a double stranded DNA b) integrase – catalyzes the integration of the double stranded DNA into the host chromosome c) protease – cleaves the polyproteins that are produced by translation of the viral mRNA d) gp120 – the glycoprotein spike that recognizes CD4 and a co-receptor on the surface of cells e) CD4 – a protein on the surface of certain cells, particularly macrophages and T helper cells, that is recognized by gp120 on the surface of HIV f) Co-receptor – an additional protein on the surface of cells that must be recognized in conjunction with CD4 in order for HIV to infect a cell; in macrophages, it is CCR5; in T helper cells, it is CXCR4 9. What factors contribute to the rapid appearance of resistance to antiretroviral drugs in HIV-infected individuals? The most important factors are the sloppy transcription of RNA by reverse transcriptase, which introduces errors (mutations) at a high rate, and the extremely high rate of virus production. The two of these factors result in the production of 1-10 billion genetically different viruses each day. Among that diverse population, there will almost certainly be at least one virus that is resistant to any particular drug. 10. What are the major routes for transmission of HIV? The major routes of transmission are 1) sex; 2) perinatal transmission (i.e. during birth); 3) injection drug abuse; 4) blood transfusions with infected blood (not really any more) 11. After a person is infected with HIV, when can they transmit the infection to another person? At any time. The most highly infectious period is probably the initial few weeks, before the immune system starts to fight effectively. 12. What are some of the major problems in dealing with AIDS in Africa? The major problem is MONEY. It is expensive to treat HIV, and to provide the right kind of follow-up that allows identification of emerging resistant strains and appropriate changes in treatment strategy. It is also expensive to buy formula to prevent the transmission of HIV through breast milk. There are also problems with acceptance of intervention strategies, both by individuals and by governments. Finally, there are many societal traditions and attitudes that play a role, particularly in decreasing the acceptability of condoms. 13. What is HAART? Is it effective? Why? HAART stands for highly active anti-retroviral therapy. It can be very effective when patients comply with their medication schedules, which can be quite complicated. It is effective because it combines three different anti-HIV drugs. The probability of a patient harboring a virus capable of resisting any one of the drugs singly is quite high, but the probability of a particular virus being resistant to two of the drugs is lower, and resistance to all three of the drugs is extremely unlikely. 14. Why is it necessary to get a “flu shot” every year? The surface proteins of influenza virus – the hemagglutinin and neuraminidase – undergo “antigenic drift”. That is, the sequences of these proteins change gradually through mutations. New versions are selected for because they can avoid the immune system response that has developed to combat previous strains. So, a flu shot will provide protection against only a particular virus, and the virus will have changed enough by the next year that memory cells generated against the previous version will not be effective against the new one. In addition, occasionally viruses undergo “antigenic shift”, which is a much more dramatic change in surface proteins which also makes it possible for the virus to avoid the immunity generated toward previous strains. 15. What are the functions of the hemagglutinin and neuraminidase molecules on the surface of influenza virus? The hemagglutinin molecules bind to sialic acids on the surfaces of host cells, a step that is necessary for viruses to be taken into the cells. Neuraminidases are enzymes that cleave sialic acids; their main job is to cleave sialic acids derived from the host cell membranes off of the new virus particles so that they don’t stick together.