Chapters 15-20 Review Questions
16.1. Explain how mutant porins could help to make lactamases more effective. Could mutant porins team up with other types of resistance mechanisms to increase the effectiveness of the resistance mechanism?
the gram-negative bacteria confine their β-lactamases to the periplasm and have porins that restrict the entry of β-lactams into this region, they can achieve the same level of resistance with a lower level of enzyme than gram-positive bacteria. Unlike porin mutations, which confer resistance to many different antibiotics, β-lactamases are much more specific and are usually active against only a subset of β-lactam antibiotics Some gram-negative bacteria, such as E. coli strains, tend to be naturally resistant to macrolides, probably because their porins do not admit the antibiotic into the periplasm. First, some types of resistance mechanisms, such as mutations in gram-negative porins or some types of antibiotic efflux, confer resistance to more than one type of antibiotic. bacteria can accumulate mutations that further restrict the diffusion of antibiotics through the outer membrane and increase resistance, and since some types of porins are relatively nonselective, a single porin mutation can confer resistance to more than one type of antibiotic. For a long time, the importance of mutations in porins as a mechanism of resistance was somewhat underappreciated because this type of resistance usually confers increases in resistance of only 5- to 10-fold.
15.5. Many of the aminoglycoside antibiotics are much less effective against Escherichia coli under anaerobic conditions than under aerobic conditions. Assume that the rates of protein synthesis are about the same in both cases and that the antibiotic inhibits protein synthesis in vitro. How would you explain the reduced effectiveness under anaerobic conditions?
there may be multiple redundant transporters that can take up this class of antibiotic. An interesting observation is that some bacteria become much more resistant to aminoglycosides when they are growing under anaerobic conditions. Escherichia coli becomes almost 10 times more resistant to aminoglycosides when growing anaerobically, and many anaerobes are totally resistant to aminoglycosides. In both cases, the resistance appears to be due to drastically reduced uptake of the antibiotic.
16.8. Why can transfer of DNA by conjugation cross genus lines, whereas transfer of DNA by natural transformation or phage transduction is usually limited to a few closely related organisms?
transformation may be transferring the mutant penicillin-binding proteins that make S. pneumoniae resistant to penicillin. However, the spread of resistance genes, especially between members of different species, can be a much more serious general threat. Accordingly, attention has tended to focus on transfer of resistance genes by conjugation. Conjugation is the direct cell-to-cell transfer of DNA through a protein complex that transits the membranes of two bacteria
16.18. Production of a new penicillin-binding protein would reduce the affinity for which of the following antibiotics: methicillin, streptogramin, chloramphenicol, ciprofloxacin, tetracycline, vancomycin, erythromycin, or penicillin.
vancomycin,
16.12.Indicate which of the following statements are true or false: d. Antibiotic resistance is clinically important because it results in increased costs.
• Treatment of choice is methicillin or derivatives (eg. Cloxacillin) -- cost ≈ $30.00 for standard 10-day course Antibiotic resistance→ • Treatment options are limited - Vancomycin - $200.00 for 10-day intravenous course - Total cost to treat 1 hospitalized isolated MRSA patient ≈ $14,000 • Total cost associated with MRSA in Canada: $42-59 million/yr
15.1. How do antiseptics, disinfectants, and antibiotics differ from each other?
''Disinfectant'' is the term used to describe antimicrobial compounds applied to inanimate objects and surfaces. ''Antiseptic'' is the term used to describe antimicrobial compounds applied to the skin, e.g., hand-washing preparations used in hospitals and doctors' offices and the waterless hand sanitizers that are now widely available in public locations. Antibiotics (''agents against life'') are low- to mediummolecular- weight compounds that kill or inhibit the growth of bacteria and can be ingested by or injected into humans and animals with minimal side effects. In contrast to most disinfectants and antiseptics, antibiotics generally interfere with a specific bacterial enzyme or process, such as the enzyme DNA gyrase, which negatively supercoils the genomic DNA, or the transpeptidase enzymes that cross-link peptidoglycan in the cell wall
20.11. Which bioterror agents persist in the environment? Explain your answer. What steps would be necessary to clean up or live in these contaminated environments?
- Anthrax Spores are long lived - Some other bacteria (eg. Francisell and Brucella) and viruses (eg. Poxviruses, lassa fever virus and hantaviruses) are relatively stable in the environment. - Proteins, like toxins, are the least stable Proteins are the worst. Susceptible to degradation, enzymes, heat.
16.10. Give a possible set of bacterial factors (or lack thereof) and what properties they have that would explain an increase in the 50% inhibitory concentration for tetracycline by 1,000-fold in an organism.
- Increased inactivation of the drug by modification - Increased efflux of the drug from the bacterial cell - modification of the bacterial membrane so that the drug cannot be taken up as well - modification of the target receptor so that the drug does not bind as well to it.
17.12. Do vaccines necessarily work better if they target virulence factors than if they target molecules not involved in virulence? Explain why or why not.
- The purpose of vaccines in to prevent infection in the first place and/or to make the defenses of the body more effective. - The Proteins that are targets of antibodies and cytotoxic T cells may be virulence factors, but they need not be. - the only criterion it that the antibodies or CTLs that target them provide a protective response.
15.8. For the following antibiotics, briefly describe how each kills or inhibits the growth of bacteria: -lactams, glycopeptides, aminoglycosides, tetracyclines, quinolones, and macrolides
-Lactams (penicillins, cephalosporins, carbapenems, monobactams) Inhibit transpeptidation step in peptidoglycan synthesis; bind penicillin-binding proteins; stimulate autolysins - Glycopeptides Inhibit transglycosylation and transpeptidation steps in peptidoglycan synthesis by binding DAla- D-Ala - Aminoglycosides Bind 16S rRNA in 30S subunit of bacterial ribosome - Tetracyclines Bind 16S rRNA in 30S subunit of bacterial ribosome; disrupt bacterial membrane - Macrolides/ lincosamides Bind 23S rRNA in 50S subunit of bacterial ribosome - Fluoroquinolones Bind DNA gyrase - Metronidazole Nicks bacterial DNA and interferes with DNA replication
18.7. S. pneumoniae depends on_____ and____ to evoke the inflammatory response for tissue damage and entry into the bloodstream.
...S. pneumoniae depends on cytolytic toxin pneumolysin and hydrogen peroxide to evoke the inflammatory response for tissue damage and entry into the bloodstream.
19.4. Why is there no vaccine against E. coli neonatal meningitis?
...The K1 capsule is poorly immunogenic because sialic acid is a molecule that is widely found on human cells. It confers serum resistance and also has some role in aiding the bacteria to cross the blood-brain barrier. In addition, the inefficiency of the neonates' alternative complement system, as well as a less developed adaptive immunity, hampers their defense against encapsulated bacteria
19.7. Why might P. aeruginosa produce so many virulence factors? Why is cell-to-cell signaling, which controls the production of many of these factors, so important? Could these signaling systems become a target for antibiotics?
A group of pathogenic microbes can sound the alarm for others - Each set of virulence factors need to be separately regulated to response appropriately to whatever environmental conditions the microbe encounters. ie. cell to cell signally is required for the regulation. - since the signaling systems regulate virulence factors, they could be good targets for antibiotics
17.8. Consider a bacterium that is ingested via contaminated water and locally infects the small intestine. What type of vaccine would be most useful against this bacterium? What type of immune response would this vaccine elicit?
A vaccine that would produce anti-toxins if it were an toxicoinfection such as that for Pertussis. catalytically inactive toxins to deliver epitopes in candidate vaccines that require stimulation of both humoral and CTL responses
18.5. On one particularly busy evening, you forget to put a casserole in the refrigerator after dinner. Even though the food has not been refrigerated, it still ''looks'' okay, and you decide to eat the casserole the next day. A. If the casserole is contaminated with S. aureus, will reheating protect you from food poisoning? Provide your rationale. B. If the casserole is contaminated with Clostridium botulinum, will reheating protect you from food poisoning? Provide your rationale.
A. S. aureus, If cooked enough to kill the bacteria the food would be safe to consume. Incubation takes place in the intestines S. aureus creates an enterotoxin that causes toxic shock due to superantigen connections. This requires a humoral response.. B. Clostridium botulinum - Exotoxins produced by C botulinium are heat stable and can be produced anaerobic environment outside of the host. Intoxication of this can happen even if the microbe has been killed. The toxin remains
17.13. Why might an IgG response to Salmonella enterica serovar Typhi be ineffective?
Ag conversion? Transposons? MALTs associated?
17.1. In the former Soviet Union, as it began to fall apart in the early 1990s, there were great unrest and population dislocations. Suddenly, the incidence of diphtheria began to rise to alarming proportions. This might be understandable if all the cases were in young children who might have fallen through the cracks of a compromised health system (which had actually been of high quality, at least in some areas, during earlier days), but many of the cases were in adults. It is still not clear what happened, but speculate on how the diphtheria vaccination program in the Soviet Union might have failed.
An unpleasant reminder that diphtheria can kill adults occurred much more recently when diphtheria made an unexpected appearance during the early 1990s in the former Soviet Union, causing an epidemic in which many of the victims were adults. This epidemic illustrates another set of circumstances that can shift the age range of the disease. As the former Soviet Union began to break up after the end of the cold war and civil strife between various ethnic and religious groups became all too common, the public health programs that had been in place in previous years were disrupted, including vaccination programs. Also, defective lots of the vaccine were probably being used even in the days before the breakup of the Soviet Union. The administration of an effective immunization program requires a large national infrastructure with the capacity to facilitate coherent planning, coordination, financing, public information, and government industry cooperation for the proper testing, production, distribution, use, and monitoring of vaccines. In the United States, this process requires the proper coordination and functioning of over 20 federal agencies, not including state departments of health, vaccine and biotechnology companies, professional medical facilities, voluntary organizations, and public and private health care officials. A clear example of what can happen when this complex infrastructure fails is the diphtheria epidemic that swept through the former Soviet Union following its collapse in the early 1990s.
16.13. Which of the following is the easiest way for bacteria to develop antibiotic resistance? A. Generate a mutation to alter the target protein. B. Add a functional group to the antibiotic. C. Acquire a conjugative plasmid harboring an antibiotic resistance gene. D. Mutate the gene that regulates the antibiotic resistance genes. E. Mutate the efflux pump so that it pumps out the antibiotics faster than they can accumulate in the bacterial cell.
C. The Acquisition of Plasmids with resistance might be the easiest way to gain the resistance.
16.4. Some target modifications require only one or a few mutations (e.g., resistance to fluoroquinolones), yet others, such as protection of the ribosome by methylation of rRNA, require new enzymes. Explain the difference.
DNA gyrase is an essential enzyme, but mutations that impart resistance allow sufficient function of the gyrase for nearly normal growth. Similarly, resistance to rifampin is caused by mutations that result in amino acid changes in the β-subunit of RNA polymerase. These amino acid changes reduce the affinity of the antibiotic for the RNA exit channel in RNA polymerase. Methylation of A2058 prevents hydrogen bond formation, the antibiotics fail to bind tightly to the ribosome exit channel, the tunnel remains unblocked by the antibiotic, and resistance results
16.2. Efflux pumps seem very energy inefficient. Why do bacteria not simply fail to take up antibiotics into the cytoplasm?
Due to the ability of some antibiotics to defused directly across the cellular membrane with their concentration gradient. The cell would have to be non-permiable to the antibiotic.
16.6. In the case of gram-negative bacteria, efflux pumps are generally coupled with outer membrane proteins. Why is this necessary?
Efflux pumps fall into two structural classes. The majority are antiporters that use the uptake of protons (H⁺) as the source of energy to pump the antibiotics and other small molecules from the cytoplasm. Some efflux pumps are ABC transporters, which are multisubunit complexes that use ATP hydrolysis to power the pump. The structures of efflux pumps of gram- positive bacteria are usually relatively simple, because these pumps only need to remove the antibiotic to the outside of the cell. In contrast, efflux pumps of gram-negative bacteria often consist of proteins in the inner membrane, periplasm, and outer membrane that channel the antibiotic outside of the cell.
16.5. Why does mutation to resistance occur within a short time in some cases (e.g., erythromycin or penicillin) and only over a period of decades in other cases (e.g., vancomycin)?
If the bacteria have to become resistant by mutating an antibiotic target and the change requires multiple mutations, it would take longer for the bacterium to become resistant to the antibiotic than if the bacterium acquired a resistance gene by horizontal gene transfer or could become resistant with only one or a few mutations. Some resistance is acquired via horizontal gene transfer and happen very quickly. Others are due to efflux pumping in addition to small mutations over numerous generations. In this case the resistance develops of multiple generations in vertical gene transfers.
16.9. Some integrons that contain disinfectant resistance genes or mercury resistance genes, as well as antibiotic resistance genes, have been found. What is the potential significance of this association?
Integrons are usually transposons, but they have an extra feature. They contain an integrase gene and an attachment (att) site, in addition to insertion sequences. The integrase integrates circular DNA segments containing a promoterless single open reading frame (gene cassettes) into the att site. In effect, integrons create operons by sequential integration of the gene cassettes. The att site is a promoter provided by the integron that allows the operon genes to be expressed. These disinfectant resistance genes or mercury resistance genes, as well as antibiotic resistance genes, Can be stored as a cassette and expressed all at once. Leading to major increases in resistance.
17.11. Some scientists are looking into the strategy of using passive immunization to control bacteria that are resistant to many antibiotics. How would such a strategy work? (Recall that passive immunization is the injection of preformed antibodies into a patient.)
It is feasible that passive immunization could be extended to treat infections caused by highly drug-resistant bacteria, such as S. aureus. For certain high-risk groups, such as the elderly and the very young, vaccines have offered significant protection against some bacterial pathogens, such as the capsule and conjugated-capsule vaccines directed against S. pneumoniae. Passive immunization has been receiving much more attention recently, as physicians have finally admitted that major human killers of the preantibiotic era, such as S. pneumoniae, the most common cause of bacterial pneumonia, have become so resistant to antibiotics that patients with multidrug-resistant disease may no longer be treatable with antibiotics. Passive immunization then becomes even more important as a firewall against multiple antimicrobial-resistant microbes. Another treatment option is to provide antibodies that bind to the antiphagocytic capsule of the bacterium and enhance phagocytosis, thus destroying its ability to evade the nonspecific host defenses. More and more often, passive immunization is being invoked as a possible clinical response to multidrugresistant bacteria.
17.7. What are the advantages and disadvantages of live vaccines? Of DNA vaccines?
Live Vaccine advantages- A true representation of the antigen, No need for adjuvent, Disadvantage, Chance of infecting host, needs to be stored properly, difficulty is generating mutant strains of the bacteria that are avirulent or attenuated enough to be nontoxic and safe yet are still able to survive long enough in the body to generate a strong immune response
16.3. Efflux pumps only reduce the level of an intracellular antibiotic, they do not eliminate the antibiotic completely. Why does this make the bacteria resistant to the antibiotic?
Lowering the concentrations to sub-leathal internal levels allows for potential mutations and bacterial resistance for proceeding generations.
15.2. Why might it be harder for a bacterium to become resistant to a disinfectant than to an antibiotic?
Many antiseptics/disinfectants dissolve membranes. The bacterium would have to change its structure to become resistant. They also attack proteins nonspecifically so modification of the target would be resistant to antiseptics/disinfectants by using efflux pumps to pump them out of the cell. - It is easier for resistance to antibiotics because there is usually a single target. In contrast to most disinfectants and antiseptics, antibiotics generally interfere with a specific bacterial enzyme or process, such as the enzyme DNA gyrase, which negatively supercoils the genomic DNA, or the transpeptidase enzymes that cross-link peptidoglycan in the cell wall Antibiotics are a subclass of compounds that specifically target and disrupt bacterial cell processes. Many are complex organic compounds. Two common routes for resistance: Mutations of the target so the antibiotic doesn't bind, or express enzyme that modify the antibiotic. Disinfectants generally mess up lots of stuff (through massive oxidation for example).
18.8. S. aureus uses a system to regulate its virulence factors: are expressed during early growth phases and then downregulated as are upregulated when high density is reached.
Many of the S. aureus virulence genes, especially those encoding surface adhesins and exoenzymes, are regulated by a quorum sensing system. When cells are in the early stages of growth, analogous to exponential growth, the adhesin genes are preferentially expressed. Once the bacteria enter late exponential phase and reach a high population density, adhesin production is decreased and exoenzyme production is increased
15.3. Many of the antibiotics described in this chapter have similar types of action: they bind to an important bacterial target and inhibit its activity. Are there exceptions to this rule?
Metronidazole interferes with DNA synthesis, but it does so not by inhibiting an enzyme, but rather by making breaks in the DNA. Metronidazole, unlike other antibiotics, must first be activated by a housekeeping protein, flavodoxin, before it can attack DNA. The activated form of metronidazole could be considered to be a mutagen. Metronidazole has proved to be an antibiotic that has few side effects.
17.6. How does passive immunization differ from active immunization? Why does passive immunization not confer long-term immunity? Under what circumstances might passive immunization be preferable to vaccination for treating infections?
Passive Immunization The administration of antibodies obtained from immune animals or humans is an old solution to the problem of how to treat a patient who is not immune to a particular disease. Whereas, Active immunity immunity that develops as a result of an infection or immunization. Passive will allow for immunity while the antibodies are present but is unable to produce more of those same antibodies until a humoral response is elicited. Passive works quickly but fades quickly. Passive immunization is also gaining importance as the number of immunocompromised people has increased. This growing group includes not only people with HIV infections, but also people undergoing cancer chemotherapy or organ transplantation and those living longer. In these people, who are unable to mount an effective immune response, passive immunization may well prove to be the only option for life threatening infections.
17.9. How can recombinant DNA technology be used to enhance immunity and improve a vaccine?
Recombinant DNA technology revolutionized the development of vaccines by allowing the production and testing of recombinant nontoxic antigens, such as site-directed, catalytically inactive toxins, instead of toxoids (chemically treated or heat-inactivated toxins). The tremendous leap in understanding of the mechanisms underlying protective immunity that we have achieved in recent years has also led to the development of a new class of recombinant vaccines. This newfound knowledge, coupled with the power of molecular biological techniques, has enabled protein engineers to change the conformation and structure of the antigen. Genetic manipulation can enhance DC binding properties, stimulate desired immune responses, and enhance antigen presentation through the design of epitope-based targeting signals into the peptide sequence. For example, as mentioned above, addition of the RGD peptide (an integrin-binding motif) to the recombinant vaccine protein allowed the targeting of the antigen to DCs.
18.6. SE and TSST act as _______, crosslinking cells of the innate immune system, and are potent nonspecific activators of_________ .
SE and TSST act as Superantigen , crosslinking cells of the innate immune system, and are potent nonspecific activators of cytokine release
16.15. Fill in the blank spaces with the most appropriate words. Some members of enterococci are resistant to ,_____ a last-resort antibiotic that binds to the dipeptide of N-acetyl muramic acid within the peptidoglycan. The enterococci develop resistance by replacing this dipeptide with _______, which is not bound by the antibiotic. A novel way to overcome this resistance is to _______. The most common way antibiotic resistance genes are spread is by________ . The main source of antibiotic resistance genes is believed to be between _________bacteria found in the _______.
Some members of enterococci are resistant to *vancomycin* a last-resort antibiotic that binds to the dipeptide of N-acetyl muramic acid within the peptidoglycan. The enterococci develop resistance by replacing this dipeptide with *D-Ala-D-lactate* which is not bound by the antibiotic. A novel way to overcome this resistance is to*VanX is an enzyme that cleaves D-Ala-D-Ala but not D-Ala-Dlactate.* The most common way antibiotic resistance genes are spread is by *horizaontal gene transfer* . The main source of antibiotic resistance genes is believed to be between _________bacteria found in the _______.
20.1. Why is anthrax a ''weapon of choice'' for bioterrorists? What might make it better than smallpox or plague?
Some of the reasons bio terrorists might find anthrax an effective biological weapon are: - It is highly lethal - It is almost always deadly if not treated early - it is one of the easiest biological agent to manufacture - Spores can be produced in large quantities with a basic knowledge of the biology and can be stored for decades without losing viability. - The spores are relatively easy to develop as a weapon, since they can be easily spread over a large area in the air by missiles, rockets, artillery, aerial bombs, and sprayers. - The spores have no color, smell, or taste, so there is not immediate indication od exposure. - There is a delay before the onset of symptoms. Not very contagious as the transmission person to person is low.
18.4. Superantigens are able to elicit toxic effects throughout the body. Describe how superantigens are able to initiate these effects and how this might be an advantage to the infecting bacteria.
Superantigens are proteins that force an association between major histocompatibility complexes on antigen-presenting cells and the T-cell receptor that would not normally occur. This association can occur in the absence of presented antigens or in the presence of nonspecific antigens and is tight enough to trigger cytokine release by both cell types. If many such complexes form, enough cytokine release can occur to trigger the shock process The release of cytokines can aid the dispersion of the Ag throughout the body causing systemic infections
16.14. Bacteria can become resistant to fluoroquinolones by producing a mutation in what protein?
The Achilles heel of the fluoroquinolones is that a single mutation in DNA gyrase makes bacteria resistant to them. Overuse of fluoroquinolones in human medicine has had the predictable effect of giving rise to fluoroquinolone-resistant bacteria.
19.2. How would you formulate Koch's postulates for opportunistic pathogens?
The problem with being able to satisfy Kock's postulates for opportunistic pathogens is that the postulates demand that the infectious agents be identified only in patients and not in healthy controls and that patients who contract the agent also develop the disease
15.4. The pharmaceutical industry has been trying to develop antibiotics by solving the crystal structure of a protein target and designing molecules that fit into the active site of this target (rational drug design). So far, this strategy has not been nearly as successful as expected. Why did scientists think this would be superior to the old ways of finding antibiotics, and what are some of the reasons this approach might fail?
Using the crystal structure of the target molecule as a guide to model the potential inhibitor into the binding sites of the target protein by using computer ''docking'' simulations and then synthesize chemicals that will bind to the target molecule and inactivate it. If strong inhibitors are synthesized, they still must be transported into cells for cytoplasmic targets and be amenable to further chemical modification to optimize all of the other properties of good antibiotics.
17.2. In 2004, there was an influenza vaccine crisis in the United States, when many lots of vaccine had to be recalled. The problem was bacterial contamination. Why would this be a problem with an injectable vaccine? Would it have been a problem with an oral vaccine? If so, under what conditions? There was only one major manufacturer of the vaccine, a fact that made the shortage worse. How could this shortage of manufacturers have happened?
While many bacteria that could case disease would normally be blocked or destroyed by innate immune systems this is not the case if injected. That would give normally non-problematic microbes a free pass into the tissue and bloodstream allowing for a quick systemic infection. If the vaccine had been taken orally, the microbes would have to survive the stomach and gut before being able to infect the host. Microbes that are able to survive such conditions would only then be able to attempt invading mucosal and intestinal cells to gain access to body tissues and blood stream. As the cultivation and storage of flu vaccines are changed each year a choice must be made in which vaccine strain to make. This take to incubate and few a new strain is produced each year.
16.12.Indicate which of the following statements are true or false: a. Antibiotic resistance is a consequence of the mutagenic action of the antibiotic on the bacterium.
a. False. Resistance is a consequence of selective pressure to acquire a mutation or gene acquisition in the bacterium that promotes its survival
16.17. Enzymes, such as acetyltransferases, phosphotransferases, or adenyltransferases, would inactivate which of the following antibiotics: methicillin, streptogramin, chloramphenicol, ciprofloxacin, tetracycline, vancomycin, erythromycin, and penicillin.
acetyltransferases → streptogramin, chloramphenicol phosphotransferases →
16.12.Indicate which of the following statements are true or false: c. Antibiotic resistance is clinically important because it results in increased morbidity and mortality.
azithromycin has one rather serious drawback. It is very expensive—too expensive for many cash-strapped inner city clinics to use. It is also too expensive for many developing countries, where resistance to tetracycline and other commonly used antibiotics in bacteria that cause sexually transmitted diseases is beginning to be a serious problem
16.12.Indicate which of the following statements are true or false: b. Antibiotic resistance is clinically important because it results in increased toxicity.
b. True, Toxicity to host - After high-dose, long-term use (ex. tetracycline → discolored teeth) More resistance in bacteria could lead to higher dosages for longer periods.
17.10. What is a potential problem with the use of diphtheria toxin as an immunotoxin? Can the use of anthrax toxin overcome this problem?
because most people are immunized against DT and have antibodies that can neutralize its activity, use of DT is not ideal for most therapeutic applications. So long as the patient has not been immunized against anthrax this toxin could be used.
16.12.Indicate which of the following statements are true or false: e. Misuse of antibiotics has resulted in greater numbers of antibiotic-resistant organisms.
e. True, Clinical overuse of antibiotics → Given w/o knowledge of bacterial species or resistance profile - Lack of patient compliance (failure to take drug as prescribed) → Proper drug concentration is not maintained for long enough to kill all bacteria →Partially-resistant sub-populations survive / proliferate - Widespread non - therapeutic use of antibiotics →Problem: constant exposure of gut bacteria to antibiotics → develop reservoir of resistant bacteria in animals → transfer of resistance genes to human pathogens Solutions: • Promote responsible clinical use of antibiotics • Restrict use of some antibiotics in human & animal health • Rotate use of different types of antibiotics • Use combination antibiotics to slow development of resistance • Better public education in responsible antibiotic use
16.12.Indicate which of the following statements are true or false: f. The patient's normal microbiota can serve as a reservoir for antibiotic resistance genes.
f. True, The Patient may harbor opportunistic pathogens or other microbes that carry genetic elements or plasmids with resistance markers that can be passed off to other microbes through transduction, conjugation or transformation
17.4. In this chapter, it was asserted that failures in vaccines could occur for three reasons. Actually there are more. Can you think of some of them?
failure to elicit the anticipated protective immune response. side effects. the vaccine unexpectedly makes the disease worse. The vaccine virus may be a different serotype from the challenged virus. Maternal antibody which protects neonates may interfere with vaccine presentation. Some viruses, notably herpesviruses, are poorly neutralized and once established can spread between cells by fusion. The vaccine virus may become denatured or inactivated during storage or administration. Cell behaviour was different than that of the live virus strain. The vaccine virus may be ineffective if it is manufactured incorrectly, for example containing insufficient antigen or live virus.
16.16. How might a mutant porin in a gram-negative bacterium allow the bacterium to become less susceptible to antibiotics? How could this mutant porin help to make β-lactamases and efflux pumps more effective?
gram-negative bacteria confine their β-lactamases to the periplasm and have porins that restrict the entry of β-lactams into this region, they can achieve the same level of resistance with a lower level of enzyme than gram-positive bacteria. Unlike porin mutations, which confer resistance to many different antibiotics, β-lactamases are much more specific and are usually active against only a subset of β-lactam antibiotics
