x design based on structural and biochemical mod- sg is a practical method for designing antimicrobial , a5 well as being rapid and cost effective. {5 antimicrobial compounds are constantly being discov- end developed to deal with drug-resistant organisms and Since our ability to treat infectious diseases. However, drug, |Why is the decimal reduction time (D) important in heat sterilization? How would the presence of bac _ terial endospores affect D? = Describe the effects of lethal ionizing irradiation at the molecular level. > What are the principal advantages of using mem- brane filters instead of depth filters? ‘Why are nucleopore filters particularly useful for ~ ssolating specimens for microscopy? Describe the procedure for obtaining the minimum ‘inhibitory concentration (MIC) for a chemical that is ‘bacteriocidal for Escherichia coi. Contrast the action of disinfectants and antiseptics. ‘Why can’t disinfectants normally be used on living, issue? ‘Growth factor analogs are generally distinguished Hom antibiotics by single important criterion. APPLICATION QUESTIONS = 725 discovery and development are time consuming and expen sive. Computer drug design isan important new too! for drug discovery. v B. 4 15 . Most antibiotics are made by only certain groups of, ‘Analogs of existing drugs are often developed to be used ‘as next generation antimicrobial compounds. Explain the advantages and disadvantages of this strategy for treat- ment of infectious diseases. How can computer drug design save time and money in the search for new drugs? ‘organisms. Is this statement true? What groups of organisms make antibiotics? Describe the mechanisms of action that character- izes a B-lactam antibiotic. Distinguish between the mode of action of at least three of the protein synthesis-inhibiting antibiotics. . Why do antiviral drugs generally exhibit host toxic- iy? Define the fungi-specific targets that allow selective toxicity of chemotherapeutic agents in fungi. Outline the major mechanisms responsible for antibiotic resistance, ‘What is the ultimate origin of bacterial antibiotic resistance genes? Starting with a parent compound, describe combina torial chemistry methods used for the production of new drug analogs. Describe in a graph the experimental results you ‘would expect for the decimal reduction time of a very heat-sensitive organism. How would this raph be affected if the vegetative cells were heat- sensitive but the organism formed heat-resistant ‘endospores? What are some potential drawbacks to the use of ‘radiation in food preservation? Do you think these drawbacks could be manifested as health hazards? Why or why not? How would you distinguish between radiation-damaged and radiation-contam- ‘nated food? tation is an acceptable means of pasteurization for some liquids, Design a filtration system for pas- | teurization of a heat-sensitive liquid. Why might 0 | fitcation system be desirable over a heat pasteur- ‘zation system? Design an experiment to distinguish between a cidal and a static agent. Can you use the minimum. inhibitory concentration (MIC) test in your experi- ‘ments? Explain. ‘What tests would you perform to decide whether a chemical agent could be used as an antiseptic? As a disinfectant? Some chemicals serve both purposes. [Describe the properties of such a chemical and give ‘an example. ‘Although growth factor analogs may inhibit ‘microbial metabolism, only a few of these agents are practically useful. Many potential agents, and some that are in wide use, such as azidothymi- dine (see Table 20.5), exhibit significant host cell toxicity, Describe a growth factor analog that is effective and has low toxicity for host cells. Why fs the toxicity low for the agent you chose? Also726 ® Chapter 20 = MICROBIAL GROWTH CONTROL 2 describe a growth factor analog that is effective against an infectious disease but exhibits toxicity for hast cells. Why might a toxic agent such as AZT still be used in certain situations to treat infectious diseases? What precautions would you take to limit the toxic effects of such a drug, while maximizing the therapeutic activity? Explain your answer. Less than 1% ofall known antibiotics have any prac tical value for either research or clinical use. Indicate why this might be so. Do you think itis important to expand and continue searches for new antibi- ties? What alternatives to antibiotic treatments are, ‘or could be, available for the treatment of microbial diseases in humans, Design an experiment to examine microorganisms for the producrtion of novel antibiotics. Which group (oF groups of microorganisms would you choose? ‘Where could you find and isolate these organisms in 2 natural environment? What advantage would the production of an antibiotic provide for these organ- {sms in nature? What in vitro methods would you use to test the efficacy of your potential new antibiotics? (You may wish to review material in Sections 12.24 and 305 before answering.) Although the lactam antibiotics demonstrate clear selective toxicity for Bacteria, many groups of ‘Bacteria are innately resistant to their effects. With- out invoking bacterial resistance genes, indicate why ‘gram-negative Bacteria are resistant tothe effects of ‘mest, but not all, lactam antibiotics. Further expla why some f-lactam antibiotics are useful agains: these organisms, 3. What potential advantages might the aminoglyc™ Sides, macrolides, and tetracyclines have over peas = cillin G for chemotherapy? Explain, List the features ofan ideal antiviral drug, especi= ly with regard to selective toxicity, Do such druss exist? What factors might limit use of such a drug? Like viruses, fungi present special chemotherapess tic problems. Explain the problems inherent = chemotherapy of both groups and explain whether or not you agree with the preceding statement. Give. specific examples and suggest at least one group chemotherapeutic agents that might target Bot types of infectious agents 18, Explain the genetic basis of acquired resistance ¥s Prlactam antibiotics in Staphylococcus aureus. Desizs 4 set of experiments to reverse resistance to the frlactam antibiotics. Do you think this can be done? ‘Can your experiment be applied “in the fil proniote deselection of antibiotc-resistant orga isms? Explain. 14. Design a drug for the inhibition of HIV prot activity thats based on the structure in Figure 2027 ‘Use a mechanism diferent than competitive inhib tion atthe enzyme active site.