Microbiology Ch 10

Which category of drug is complementary to mRNA of the pathogen?

antisense nucleic acids The antisense nucleic acids are composed of the same nucleotide bases and are complementary to the mRNA.

The process of acquiring antibiotic resistance by means of bacteriophage activity is called

transduction

Which of the following will most likely contribute to the spread of a genetic mutation among bacterial species?

transformaiton Some mutations produce small changes in phenotype which may persist and spread in the absence of strong selective pressure. Similarly, some changes in phenotype may confer an advantage under certain conditions.

The tRNA molecule holding a growing polypeptide chain is at the _____.

P site P sites hold developing polypeptide chains.

Bacteria that are resistant to sulfonamide have enzymes that have a greater affinity for what?

PABA

Why would an efflux pump for penicillin located on a bacterial cell membrane not be effective at providing resistance to the drug?

Penicillin disrupts the cell wall, which is located outside of the cell membrane.

What is a superinfection?

Superinfection is a disease caused by an organism that is often an opportunist or one that was present in low numbers. Superinfection is a sequel to removal of the normal flora by antibiotic treatment. Removal of the normal flora allows opportunists that are normally present in low numbers to proliferate and produce disease.

What is meant when a bacterium is said to become "resistant" to an antibiotic?

The bacterium is neither killed nor inhibited by the antibiotic.

Rank the following events in order from GREATEST to LEAST contribution to the spread of antibiotic resistance in bacterial populations.

Horizontal transfer, vertical transfer, new mutations Cells with mutations that result in small alterations of function without complete loss of function often are at a disadvantage compared to wild-type cells, and therefore have a lower rate of reproduction. If resistance genes are only introduced into a population by the reproduction of these disadvantaged cells, the frequency will increase relatively slowly. Horizontal transfer distributes new genes widely in populations of related bacteria

Why are chemotherapeutic agents that work on the peptidoglycan cell wall of bacteria a good choice of drug?

Humans and other animal hosts lack peptidoglycan cell walls.

In examining a MRSA strain, researchers find that degraded penicillin is found in the culture medium. What is the most likely mechanism of resistance?

Production of a beta-lactamase Different MRSA strains can produce beta-lactamases, efflux pumps and expressed altered PBPs to which beta-lactams cannot bind.

Battling an EnemyLike his father and grandfather before him, Ben is a marine sergeant and proud to serve his country. He is nearing the end of his second tour of duty in Afghanistan and is looking forward to returning home to his wife and two sons. However, two weeks before he is scheduled to leave, Ben is seriously wounded in a suicide bomber's attack and almost loses his leg. He initially responds well to treatment, but three days into his recovery, his wound is obviously infected and getting worse. His doctors need to act fast. They prescribe cephalexin, which is a semisynthetic cephalosporin. The nurse swabs the wound and sends a sample to the lab for a diffusion susceptibility test.

Questions Part A-c

How might efflux pumps increase antibiotic resistance in bacteria?

Resistant bacteria can have more efflux pumps, and can have less specific efflux pumps

Which category of antimicrobial drug works by changing the shape of a ribosome?

aminoglycosides An aminoglycoside changes the shape of a 30S subunit causing the ribosome to misread the mRNA.

Which antimicrobial drugs affect the structure of the ribosome itself?

aminoglycosides, antisense nucleic acids, and oxazolidinones Each of these drugs actually modifies or prevents the formation of the complete 70S ribosome

Which of the following choices correctly matches the class of antibiotic and its mode of action? Select all that apply.

-Aminoglycosides and tetracyclines are inhibitors of protein synthesis. -Sulfonamides inhibit the synthesis of essential metabolites

Which of the following contribute to drug resistance in M. tuberculosis? Select all that apply.

-Many individuals fail to complete their entire regimen of antibiotics. -Some physicians prescribe the wrong medication, the wrong dosage, or the wrong length of time for treating tuberculosis. -In many areas, tuberculosis antibiotics are unavailable or of poor quality.

If Caleb's strain of M. tuberculosis is sensitive to antibiotic treatment, which of the following could be used to treat his infection? Select all that apply.

-streptomycin -isoniazid and ethambutol -rifampin

Prokaryotes contain _____ ribosomes

70s 70S ribosome of prokaryotes is composed of smaller 50S and 30S subunits

The cytosol of bacteria contain ____________ which has/have components different from those of the functionally equivalent structure of eukaryotes.

70s ribosomes There are many metabolic differences between humans and bacteria, including aspects of DNA synthesis, lipid synthesis and production of metabolites like folic acid. These provide possible mechanisms for chemotherapeutic strategies in addition to those acting on structures. Metabolic targets require a detailed understanding of the metabolic abilities and requirements of the specific bacterial pathogen. Some of these differences are discussed in this chapter, others are discussed in more detail in later chapters.

What is meant by selective toxicity? A. Chemotherapeutic agents should act against the pathogen and not the host. B. Chemotherapeutic agents should work on many different targets on a pathogen. C. Chemotherapeutic agents should have only one mode of action. D. Chemotherapeutic agents should work on certain types of pathogens

A. Chemotherapeutic agents should act against the pathogen and not the host.

A particular drug works by interfering with cellular metabolism in Gram-negative bacteria. How might these bacteria become resistant in a way that Gram-positive bacteria never could?

Alter porin proteins in the cell's outer membrane Altered porin proteins might prevent a drug from entering a cell; Gram-positive bacteria do not have outer membranes or porin proteins.

Why does the physician start Caleb on the antibiotic azithromycin before laboratory results come back?

Antibiotic therapy is started with a broad-spectrum antibiotic because broad-spectrum antibiotics are effective against many gram-positive and many gram-negative bacteria. Azithromycin is a semisynthetic broad-spectrum antibiotic that can be used as an alternative to penicillin, is broader in range than erythromycin, and has better tissue penetration. Dr. Bell most likely assumes that the bacterium causing Caleb's infection will be susceptible to azithromycin and that this drug should clear the infection.

Organisms are either eukaryotes or prokaryotes. Prokaryotes are further classified into the domains Archaea or Bacteria, while all eukaryotes are in the domain Eukarya. All three domains have some cell structures in common, whereas other structures are found in members of only one or two domains. Match the following descriptions of cellular structures with the type of cell in which they are found

Archea Hami Protein cell wall Bacteria peptidoglycan cell wall Eukaryotes organelles 80s ribosome in cytosol Both Eukaryotes and Prokaryotes cytoskeleton glycocalyx DNA Prokaryotes (Archaea and Bacteria) Fimbriae 70s ribosomes in cytosol

Part B One approach that is becoming more common in drug D&D is to search for antimicrobial-producing organisms in relatively pristine environments. A pristine environment is one that has been relatively unperturbed by humans and/or domestic animals. Your D&D team is searching for novel antimicrobials produced by bacteria in a remote area of a temperate rainforest in the Pacific Northwest.Which of the following terms would accurately describe your drug? Select all that apply. A. semisynthetic B. natural C. chemotherapeutic agent D. synthetic D. antibiotic

B. natural C. chemotherapeutic agent D. antibiotic You have found bacteria that demonstrate antimicrobial activity in early testing. D&D chemists on your team have successfully extracted and purified the natural antibiotic from the bacteria. Your focus now turns to microbiological evaluation of the compound.

Ben's infection is treated with imipenem. A drug such as imipenem is chemically modified from penicillin. What are non-natural drugs developed from natural drugs called? A. protein inhibitors B. semisynthetics C. antimetabolites D. fungal enzymes

B. semisynthetics Semisynthetics are chemically altered antibiotics that are more effective, longer lasting, and easier to administer.

Part C Typically, beta-lactam drugs affect the peptidoglycan layer on bacteria. Why would beta-lactam drugs typically be considered more active against Gram-positive bacteria and less so against Gram-negative bacteria? A. Beta-lactam drugs attack the capsule, and many Gram-positive bacteria have a capsule. B. The Gram-positive bacteria are more susceptible to all antibiotics. C. The cell walls of Gram-positive bacteria have a thick peptidoglycan component. D. Gram-positive bacteria have an inner and outer cell membrane that makes them less susceptible to beta-lactam drugs.

C. The cell walls of Gram-positive bacteria have a thick peptidoglycan component. The damage from beta-lactam action affects a greater proportion of the Gram-positive cell walls than Gram-negative cell walls.

Part A The project that you are working on was initiated in response to the growing threat of antibiotic resistance in both hospital and community settings. Even in the early discovery and development phase, it is important to think ahead to try to minimize the likelihood that bacteria will be able to evolve resistance to your new drug. Understanding how resistance emerges is an essential part of this process.Which of the following statements is NOT true regarding the evolution of antibiotic resistance in bacteria? A. Resistance can emerge due to mutations in chromosomal genes. B. Bacteria can acquire plasmids conferring resistance through horizontal gene transfer. C. The exposure of bacteria to an antibiotic causes the bacteria to produce resistance genes. D. Due to natural genetic variation within populations, resistant bacteria will be present--even in the absence of antibiotic.

C. The exposure of bacteria to an antibiotic causes the bacteria to produce resistance genes. In the absence of a selective pressure, such as a certain drug, bacteria that possess genes that confer antibiotic resistance will reproduce more slowly due to the energy expense of maintaining resistance genes. In the presence of a selective pressure, however, the sensitive bacteria will be killed and the bacteria that possess genes that confer antibiotic resistance will have a reproductive advantage. Therefore, over time the genes for resistance will increase in frequency within the population.

What causes thrush?

Candida albicans Candida albicans causes thrush, especially in patients taking antibiotics. Antibiotics kill off the normal bacterial flora, and then the yeast can proliferate.

Dr. Paul Ehrlich observed that the differential stain developed by Dr. Gram suggested bacteria could be killed differentially by chemicals (Chapter 1). He called these potential antibacterial agents "magic bullets". Which among the following cell features of bacteria are potential targets for Dr. Ehrlich's "magic bullets" due to significant difference or absence from humans? Choose all that apply.

Cell wall Ribosome

Part C One aspect that must be evaluated during the development phase is the interaction of your drug with the host (i.e., what effect will the drug have on human cells?). There are several important factors to consider in this interaction, including the selective toxicity of your potential drug.Which of the following statements most accurately describes the principle of selective toxicity? A. Selective toxicity refers to the fact that the toxic effect of an antimicrobial varies depending upon the environmental conditions under which it is administered. B. Selective toxicity refers to the fact that antimicrobial agents target a particular microbial structure, molecule, or pathway to exert their effect. C. Selective toxicity describes the fact that antimicrobials are more effective against certain microbes compared to others. D. Selective toxicity refers to the ability of an antimicrobial to kill microbes with minimal damage to the host.

D. Selective toxicity refers to the ability of an antimicrobial to kill microbes with minimal damage to the host. Your studies using both in vitro and in vivo models indicate that your drug has a high selective toxicity. This means that it is effectively toxic against bacterial pathogens while having minimal toxic effects on the host (eukaryotic) cells.

Part A Why do the beta-lactam drugs affect bacteria but NOT human cells? Why do the beta-lactam drugs affect bacteria but NOT human cells?

D. The beta-lactam antibiotics act on bacterial cell walls; human cells do not have cell walls. Beta-lactams prevent NAM subunit cross-linkages affecting the peptidoglycan layer of the Gram-positive cell wall. Human cells do not have cell walls; therefore, beta-lactam drugs do not affect them.

Quinolones and fluoroquinolones act against what bacterial target?

DNA gyrase

When a nurse rubs your skin with rubbing alcohol prior to administering an injection, what process(es) is he carrying out? Select all that apply.

Degerming Antisepsis Preparing skin for an injection involves rubbing, which contributes to degerming, and the use of alcohol, which contributes to antisepsis.

Many MRSA strains are sensitive to other antibiotics. Which of the following methods would be the best way to evaluate sensitivity to other antibiotics?

Disk diffusion The key point in identifying treatment options for MRSA is to determine which non-beta lactam antibiotics it is sensitive to.

Why does Dr. Bell start Caleb on HIV therapy in addition to the antibiotics used to treat the tuberculosis?

Dr. Bell prescribes Caleb HIV therapy because the virus is not affected by the antibiotics used to treat tuberculosis.

Membrane transport proteins are required for which mode(s) of antibiotic resistance?

Efflux pumps, beta-lactamases, and modification of porins all utilize membrane transport proteins.

Which of the following does not spread drug resistance throughout a population of bacteria?

Effux pumps Efflux pumps can remove a drug from a cell, but do not spread resistance from one cell to another.

Which of the following statements is MOST correct regarding the development of antibiotic resistance in populations of bacteria?

Exposure to antibiotics selects for the members of a bacterial population which already have a resistant phenotype. The appearance of bacteria resistant to antibiotics is the result of natural selection acting on populations of bacteria which include a number of genetic variants.

In order to gain FDA approval for your drug, you must elucidate its mechanism of action (MOA). MOA refers to the particular pathway/ process/molecule that will directly be impacted by your drug. Current antibiotic therapies against bacterial infection use one of five characterized mechanisms. Match each antibiotic (and its functional description) with the appropriate mechanism of action.

Inhibition of cell wall synthesis = penicillin Inhibition of protein synthesis = streptomycin Disruption of cytoplasmic membrane = gramicidin Inhibition of general metabolic pathway = sulfanilomide Inhibition of DNA or RNA synthesis = trilfuridine

Why is polymyxin only used on the skin?

It can also damage living human cell membranes, but the drug is safely used on the skin, where the outer layers of cells are dead.

Mycoplasmas are bacteria that do not contain cell walls. These bacteria are naturally resistant to which of the following?

Methicillin Methicillin is a beta-lactam and targets growing peptidoglycan layers in the cell wall. Since mycoplasmas do not have a cell wall, they are naturally resistant to beta-lactams.

A common mechanism for antibiotic resistance is alteration of the molecule targeted by the antibiotic. Very small changes in the structure to extensive alterations may produce a gene product on which the antibiotic has limited effect. Match the type of point mutation with the type of damage it is most likely to produce.

Missense: Small change in gene product which may or may not alter function. Frameshift: Extensive change in gene product structure and function. Nonsense: Premature termination of gene product with probable loss of function. Silent: No change in gene product Both frameshift and nonsense mutations are likely to produce proteins that do not function or function aberrantly, while missense mutations generally produce small changes. Depending on their location in a polypeptide, missense mutations may have no effect to significant effect on function, and are unlikely to result in major changes in the structure of a polypeptide.

Clostridium difficile is a common healthcare associated infection. It is a Gram-positive spore-forming anaerobe that is associated with antibiotic therapy. It is most commonly transferred between patients on the hands of health care workers. Based on this information, rank the following prevention and control strategies from most beneficial (1) to least beneficial (4).

Most likely to be beneficial to least likely to be beneficial Hand hygiene with soap and water Use of gloves Use of approved chemical disinfectants in patient rooms Hand hygiene with alcohol gels

Point mutations are those that alter a single base pair or base location, and include substitutions and frameshift mutations. They can range in severity from no phenotypic change to complete loss of function. Rank the following point mutations in order of least damaging to most damaging if they occur in the middle of the coding sequence of a polypeptide.

Silent Missense Frameshift Nonsense Premature termination is most likely to result in complete loss of gene product function while frameshifts produce polypeptides with significantly changed sequences of amino acids. Frameshifts may also result in premature termination, usually many codons downstream of the frameshift

Why is it difficult to find good chemotherapeutic agents against viruses?

Viruses depend on the host cell's machinery, so it is hard to find a viral target that would leave the host cell unaffected.

Which of the following is NOT an important consideration when preparing to use a chemical to disinfect a diaper changing table in a public restroom?

Whether or not hand sanitizer is available at the changing table Using a chemical disinfect generally requires a clean surface and a particular duration of contact with the chemical. It is also important to ensure that the chemical won't damage the surface to be disinfected.

R-plasmids are most likely acquired via Check all that apply.

bacterial conjugation

Which of the following is a beta-lactam antibiotic?

cephalothin

How did the multidrug resistant strains of Mycobacterium tuberculosis, like those in the prison, arise?

conjugation and exchange of resistance factors located on plasmids Correct. Horizontal gene transfer of plasmid resistance factors is one highly effective method of spreading multidrug resistant strains throughout hospitals and prisons.

What is the therapeutic index?

drug dose the patient can tolerate divided by the effective dose Correct. TI = drug dose tolerated by patient divided by the effective dose

A patient is infected with a bacterium that produces the enzyme beta-lactamase; this enzyme

inactivates penicillins, carbapenems, and cephalosporins. Beta-lactamase destroys the beta-lactam ring of penicillins, carbapenems, and cephalosporins; the functional part of these drugs is a beta-lactam ring.

Which category of antimicrobial drug essentially acts to stall a ribosome as it reads mRNA?

macrolides Macrolides block the movement of a ribosome along mRNA, so the E site is never emptied and polypeptide formation is stopped.

Not all changes in amino acid sequence are deleterious, some may even be beneficial. Which of the following point mutations is most likely to alter a protein product without destroying its function?

missense Changes in gene sequences that alter function without destroying the function of a polypeptide may become permanent in the genome of the organism.

A patient has been diagnosed with a disease caused by a drug-resistant strain of bacteria. What is a likely way that the bacterium initially acquired resistance?

mutation Genetic mutations can change the phenotype of a cell, which might confer resistance to a particular drug.

Which antibiotic is overcome by beta-lactamases?

penicillin

The ____________ is a defining characteristic of bacteria which is not found in eukaryotes and is therefore a good choice for chemotherapeutic agents.

peptidoglycan cell wall The composition of the bacterial cell wall is one of the defining characteristics of the domain Bacteria.

Chloramphenicol blocks the action of the large (50S) subunit. This essentially _____

prevents the formation of peptide bonds Without the formation of peptide bonds, amino acids diffuse away and protein synthesis ceases.

Which drug inhibits RNA production and colors body secretions red-orange

rifampin Correct. Rifampin directly inhibits transcription and imparts a red-orange color to body secretions

Which of the following mutations would not result in antibiotic resistance?

silent mutation

What is microbial antagonism?

the ability of the normal flora to outcompete and outgrow pathogens Correct. Normal flora are well adapted to their niche. These bacteria may utilize nutrients more quickly or produce bacteriocins that inhibit growth of other microbes.

When a patient is treated with antibiotics, __________.

the drug will kill or inhibit the growth of all of the sensitive bacterial cells

Antimicrobial drugs are selectively toxic. This means _____.

the drugs are more toxic to the pathogens than to the patient They selectively target physiological and anatomical differences between pathogens and patients.

Which of the following classifications would best describe Candida albicans?

yeast Candida albicans is a unicellular chemoheterotroph that has a nucleus.