Chapter 12: Antimicrobial Agent Mechanisms of Action and Resistance. All Answers

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MULTIPLE CHOICE 1. Relatively nontoxic antimicrobial therapeutic agents include all of the following except: a. heavy metals. b. antibiotics. c. preservatives. d. antiseptics. A Heavy m... etals, although they have antimicrobial properties, are highly toxic to patients. Antimicrobial agents include antiseptics, antibiotics, preservatives, sterilants, and disinfectants; all have the capacity to kill or suppress the growth of microorganisms. REF: 255 OBJ: Level 1: Recall 2. Antibiotics work by targeting all of the following except: a. DNA replication. b. bacterial plasmid DNA. c. bacterial cell wall. d. RNA transcription. B Antibiotics target the bacterial cell wall and the cellular machinery responsible for the synthesis of precursor molecules; cellular targets include DNA replication, RNA transcription, and mRNA translation. Although numerous antibiotic classes exist with different modes of action, bacteria evolved and adopted numerous strategies to counteract the action of antibiotics. REF: 255 OBJ: Level 1: Recall 3. Which of the following public health issues is uniting scientists from across the world to develop strategies to address it? a. Reclassifying bacteria according to their genomes b. The shortage of low toxicity antifungal drugs c. Antibiotic resistance d. Emerging pathogens C Antibiotic resistance emerged soon after the discovery of antibiotics and is associated with the overuse of antimicrobial agents. Although antibiotics allow the medical community to make great strides in human health and welfare, their use also causes selective pressure, allowing only the fittest and less susceptible bacterial populations to thrive. Antibiotic resistance and its associated clinical failure is an issue of public health concern that is uniting scientists from across the world to develop strategies to address it. REF: 255 OBJ: Level 1: Recall 4. Mechanisms that mediate intrinsic antibiotic resistance include all the following except: a. cell wall impermeability. b. biofilm formation. c. expression of genes mediating inactivating enzymes. d. alternate biosynthetic pathways. D Antibiotic resistance may be characterized as intrinsic and is an inherent genotypic characteristic of the microorganism disseminated vertically to progeny. Mechanisms that mediate intrinsic resistance to antibiotics include cell wall impermeability, efflux, biofilm formation, and the expression of genes producing inactivating enzymes. REF: 263 OBJ: Level 1: Recall 5. Antibiotic mechanisms of action target all the following except: a. blocking the Embden-Meyerhof pathway. b. bacterial cell wall synthesis. c. DNA replication. d. RNA transcription. A Although the classification scheme and number of antibiotics is complex and continues to expand as new classes emerge or existing classes are modified, their mechanisms of action target bacterial cell wall biosynthesis, folate synthesis, DNA replication, RNA transcription, and mRNA translation. These are logical targets critical to the survival of the microorganism. REF: 255 OBJ: Level 1: Recall 6. Both gram-positive and gram-negative bacteria have an inner cytoplasmic membrane that is composed of: a. nucleotides. b. phospholipids and proteins. c. cholesterol and carbohydrates. d. lipopolysaccharides. B The cytoplasmic membrane, composed of phospholipids and proteins, surrounds the cytoplasm, acts as an osmotic barrier, and is the location of the electron transport chain responsible for energy production. REF: 258 OBJ: Level 1: Recall 7. In gram-positive bacteria, what is substantially thicker and more multilayered than in gram-negative bacteria? a. Lipopolysaccharide b. Phospholipid c. Peptidoglycan d. Cholesterol C In gram-positive bacteria, the peptidoglycan is substantially thicker and more multilayered than in gram-negative bacteria. REF: 259 OBJ: Level 1: Recall 8. The outer membrane of gram-negative bacteria is composed of: a. lipopolysaccharides, phospholipids, and porin proteins. b. peptidoglycan, phospholipids, and proteins. c. enzymes, cholesterol, and carbohydrates. d. carbohydrates, peptidoglycan, and proteins. A The outer membrane of gram-negative bacteria is composed of lipopolysaccharides, phospholipids, and porin proteins, and it is separated from the cytoplasmic membrane by a periplasmic space. REF: 259 OBJ: Level 1: Recall 9. All of the following are -lactam antibiotics except: a. penems. b. monobactams. c. carbapenems. d. monoterpenes. D -Lactam antibiotics, such as penems, cephems, carbapenems, and monobactams, act by binding to penicillin-binding proteins, which are bifunctional transpeptidases/transglycosylases that cross-link peptidoglycan. Without this cross-linking of the peptidoglycan, the cell walls break down. REF: 259 OBJ: Level 1: Recall 10. Penicillins, cephalosporins, monobactams, and carbapenems all have what ring in their structure that is responsible for inhibiting the transpeptidation reaction, resulting in bacterial lysis and cell death? a. Benzene b. -Lactam c. -Lactam d. -Cephems B The active moiety of -lactam antibiotics is the four-membered -lactam ring—a ring structure found in penicillins, cephalosporins, monobactams, and carbapenems. The four-membered ring represented by the structure labeled -lactam functions as a structural analogue of the normal substrate, and inhibits the transpeptidation reaction, resulting in bacterial lysis and cell death. REF: 259 OBJ: Level 2: Interpretation 11. What is the mechanism of action of the glycopeptides (vancomycin and teicoplanin)? a. The glycopeptides inhibit folate synthesis and prevent the bacteria from using this as an energy source. b. The glycopeptides interfere with DNA replication and disrupt the protein synthesis operation. c. The glycopeptides bind to the substrate of the transpeptidation enzyme and disrupt the cell membrane construction. d. The glycopeptides interfere with transfer RNA production and disrupt the protein synthesis operation. C Glycopeptides, such as vancomycin and the investigational drug teicoplanin, act by complexing the noncross-linked peptide strands of peptidoglycan units having the pentapeptidyl tails ending in D-ala-D-ala. This prevents their incorporation into the peptidoglycan chain by blocking the transpeptidation step. Glycopeptides bind to the substrate of the transpeptidation enzyme, and penicillins bind to the enzyme mediating the transpeptidation reaction. REF: 260 OBJ: Level 1: Recall 12. Which antibiotic inhibits folate synthesis, which provides the essential precursor molecule, pyridine thymidylate, needed in DNA synthesis? a. Vancomycin b. Quinolones c. Aminoglycosides d. Sulfamethoxazole D Sulfamethoxazole blocks the step leading to the formation of one of the enzymes needed for folate synthesis. Because folate synthesis forms the essential precursor molecule—pyridine thymidylate, needed in DNA biosynthesis—the bacteria cannot replicate its DNA and dies. REF: 260 OBJ: Level 2: Interpretation 13. Which antibiotic affects the DNA replication by targeting topoisomerases II and IV, enzymes considered important in controlling DNA replication? a. Glycopeptide b. Sulfamethoxazole c. Trimethoprim d. Quinolone D Quinolones disrupt the DNA replication cycle of bacteria by targeting topoisomerases II and IV. Interestingly, the targets of quinolones appear to be selective, targeting DNA gyrase in gram-negative bacteria and topoisomerase IV in gram-positive bacteria. However, newer quinolones appear to have high affinity for both targets. REF: 261 OBJ: Level 2: Interpretation 14. Which antibiotic interferes with DNA transcription by blocking of RNA chain elongation? a. Rifampin b. Quinolone c. Trimethoprim d. Glycopeptide A Rifampin, a synthetic derivative of rifamycin B, is used in combination with other antibiotic classes to treat Mycobacterium tuberculosis by targeting transcription of DNA. The target of rifampin in M. tuberculosis is the RNA polymerase  subunit at an allosteric site, with the subsequent blocking of RNA chain elongation. As a result, RNA transcription is aborted at the initiation step. REF: 261 OBJ: Level 2: Interpretation 15. All of the following antibiotics target the 50S ribosomal subunit to prevent mRNA translation in the bacteria except: a. macrolides. b. quinolones. c. oxazolidinones. d. streptogramins. B The bacterial ribosome is a primary target of numerous antibiotics with some targeting the 30S ribosomal subunit (i.e., aminoglycosides, tetracyclines, glycylcycline) and others the 50S ribosomal subunit (i.e., macrolides, oxazolidinones, streptogramins). REF: 261 OBJ: Level 2: Interpretation 16. These antibiotics are cationic carbohydrate-containing molecules, and their positive charge provides the basis for their interaction with the 30S ribosomal subunit. What class of antibiotic are these? a. Sulfamethoxazole b. Trimethoprim c. Aminoglycosides d. Peptidoglycans C Aminoglycosides are cationic carbohydrate-containing molecules, and their positive charge provides the basis for their interaction with a specific region in the 30S ribosomal subunit. Binding of the aminoglycosides to the 30S subunit prevents the docking of aminoacyl-tRNA, resulting in mistranslation and subsequent production of aberrant proteins. The incorporation of aberrant proteins into the cell wall also results in cell leakage and enhanced cellular penetration of additional antibiotic. REF: 261 OBJ: Level 2: Interpretation 17. The members of the polyketide class of antibiotics include all the following except: a. tetracycline. b. doxycycline. c. minocycline. d. oxycycline. D The clinically useful tetracyclines are members of the polyketide class of antibiotics and are represented by tetracycline, doxycycline, and minocycline. REF: 261 OBJ: Level 1: Recall 18. The members of the macrolide class of antibiotics include all the following except: a. rifamycin. b. erythromycin. c. clarithromycin. d. azithromycin. A Macrolides such as erythromycin, clarithromycin, and azithromycin target the 50S subunit specifically by binding to the peptidyltransferase cavity on the rRNA. REF: 261 OBJ: Level 1: Recall 19. Which two classes of antibiotics allow initiation and mRNA translation to begin, but they act by inhibiting peptide elongation? a. Aminoglycosides and glycopeptidians b. Aminoglycosides and quinolones c. Macrolides and tetracyclines d. Macrolides and quinolones C The macrolides and tetracyclines allow initiation and mRNA translation to begin, but they act by inhibiting peptide elongation. REF: 261 OBJ: Level 2: Interpretation 20. All of the following are recently approved classes of antibiotics that target protein synthesis except: a. sixth generation cephalosporins. b. oxazolidinones. c. streptogramin. d. glycylcycline. A The most recently approved classes of antibiotics targeting protein synthesis are oxazolidinones (linezolid), streptogramin (dalfopristin-quinupristin), and glycylcycline (tigecycline). REF: 262 OBJ: Level 1: Recall 21. Intrinsic mechanisms of resistance are: a. those that inhibit protein synthesis and RNA transcription. b. those that a bacterium acquires through plasmids. c. also called inducible enzymes. d. innate characteristics of the bacterium and transmitted to progeny. D Intrinsic mechanisms of resistance are carried in the bacterial genome and transmitted from generation to generation. REF: 262 OBJ: Level 1: Recall 22. Acquired mechanisms of resistance are those that: a. are passed on from one bacteria to the next using pili. b. are the result of a frameshift mutation in chromosomal DNA. c. result from acquisition of DNA by acquisition of extrachromosomal DNA. d. passed on from generation to generation. C Acquired mechanisms of resistance are those that result from the acquisition of DNA by transformation and recombination or by acquisition of extrachromosomal DNA and are transmitted horizontally. The latter includes acquisition of plasmids and transposons capable of disseminating resistant determinants. REF: 262 OBJ: Level 1: Recall 23. What is a porin? a. An inner membrane pore that allows proteins out into the cytoplasm b. Outer membrane pores that allow the membrane to “breathe” c. Substrates for enzymes that enable protein synthesis d. Outer membrane channels that permit the inflow of nutrients and the outflow of wastes D Porins are outer membrane channels that permit the influx of nutrients and the efflux of waste products. REF: 263 OBJ: Level 1: Recall 24. What type of pathogen may demonstrate decreases or loss of porin synthesis in combination with other resistance mechanisms, resulting in multidrug-resistant pathogens? a. Nosocomial b. Community-acquired c. Emerging d. Gram-negative A Nosocomial pathogens showing decreases or loss of porin synthesis are observed in combination with other resistance mechanisms, resulting in multidrug-resistant pathogens. In addition, the molecular size and lipophilic state affect the rate at which antibiotics traverse porins. REF: 263 OBJ: Level 2: Interpretation 25. Antibiotics that demonstrate a narrow spectrum of activity kill: a. a wide variety of bacteria. b. only a few specific types of bacteria. c. bacteria by using only one specific mechanism. d. bacteria by using a narrow spectrum of mechanisms. B Antibiotics that demonstrate a narrow spectrum of activity encompassing only gram-positive bacteria are known. These antibiotics are not effective against gram-negative bacteria because the lipopolysaccharide will not allow these antibiotics to penetrate into the cell. REF: 263 OBJ: Level 1: Recall 26. Biofilms are groups of bacteria that are irreversibly attached to surfaces and are embedded in a matrix of extracellular polymeric substances. They are commonly found on: a. native heart valves. b. dialysis shunts. c. indwelling medical devices. d. patient beds. C Bacterial biofilms are prevalent in the clinical setting, and found on numerous environmental surfaces and indwelling medical devices. REF: 264 OBJ: Level 2: Interpretation 27. Efflux pumps: a. allow nutrients into the cells through specialized channels in the bacteria’s outer membrane. b. allow electrolytes into the cells through specialized channels in the bacteria’s outer membrane. c. act as a semipermeable membrane and maintain the cell’s osmotic pressure. d. function as transporter proteins involved in the removal of toxic substances from the interior of the cell to the external environment. D Efflux pumps are found in gram-positive and gram-negative bacteria and function as transporter proteins involved in the removal of toxic substances from the interior of the cell to the external environment. REF: 264 OBJ: Level 1: Recall 28. The -lactam agents consist of all the following antibiotics except: a. vancomycin. b. penicillins. c. cephalosporins. d. carbapenems. A -Lactam antibiotics are the most common treatment for bacterial infections and consist of four major groups: penicillins, cephalosporins, monobactams, and carbapenems. REF: 265 OBJ: Level 1: Recall 29. -Lactamases hydrolyze -lactam antibiotics using two distinct mechanisms: those having a metallo-based mechanism of action and those with: a. ring-specific enzymes. b. a serine-based mechanism of action. c. a chromosomal mechanism of action. d. a transporter mechanism of action. B -Lactamases hydrolyze -lactam antibiotics using two distinct mechanisms: those having a metallo-based mechanism of action and those having a serine-based mechanism of action. REF: 265 OBJ: Level 2: Interpretation 30. How do the -lactamase inhibitors work? a. By structurally rearranging the -lactamase molecule so that it loses specificity for the -lactam antibiotic b. By competing with the antibiotic for porin sites on the outer membrane c. By acting as substrates for the -lactamase and reducing their effect on the antibiotic d. By acting as transport molecules to transport the antibiotic into the bacterial cell C The -lactamase inhibitors are structural analogues of the -lactam antibiotics and function as substrates for -lactamase, thus reducing their effect on the -lactam antibiotic. REF: 265 OBJ: Level 2: Interpretation 31. Acquired antibiotic resistance mechanisms include: a. efflux mechanisms. b. acquisition of new targets. c. modification of existing antibiotic targets. d. all of the above. D This section focuses on acquired mechanisms such as efflux, modification of existing antibiotic targets, acquisition of new targets, and production of enzymes that inactivate the antibiotic. REF: 265 OBJ: Level 1: Recall 32. Streptococcus pneumoniae and Streptococcus pyogenes use efflux as an effective mechanism for acquired resistance to: a. macrolides. b. peptidoglycans. c. aminoglycosides. d. quinolones. A Acquired macrolide resistance mediated by efflux, however, has recently been described in streptococci and is encoded by mefE in S. pneumoniae and by mefA in S. pyogenes. REF: 266 OBJ: Level 2: Interpretation 33. The primary mechanism of resistance to this antimicrobial class is modification by mutations encoding single amino acid changes in these targets. What antibiotic class is this? a. Macrolides b. Quinolones c. Peptidoglycans d. Aminoglycosides B Quinolones target DNA gyrase and topoisomerase IV. The primary mechanism of resistance to this antimicrobial class is modification by mutations encoding single amino acid changes in these targets. Mutations are generally localized to the amino terminal domains of gyrA and par C, termed the quinolone resistance-determining region. REF: 267 OBJ: Level 2: Interpretation 34. What type of resistance mechanism modifies the antibiotic targets and results in reduced affinity of antibiotics for their microbial targets? a. Cell wall inhibition b. Protein synthesis modification c. Enzyme alteration d. Frameshift mutation C Enzymatic alterations of antibiotic targets result in reduced affinity of antibiotics for their microbial targets and are exemplified by erythromycin ribosomal methylase and by reprogramming of the peptidoglycan termini. REF: 267 OBJ: Level 2: Interpretation 35. A young, healthy patient goes into the hospital for reconstructive knee surgery and spikes a fever the day after surgery. The doctor finds the patient has a nosocomial infection with methicillin-resistant Staphylococcus aureus (MRSA). What antibiotic should the doctor use to treat this patient? a. Penicillin b. Aminoglycosides c. Macrolides d. Vancomycin D The glycopeptide vancomycin is used to treat enterococci that cause endocarditis and is the drug of choice for the treatment of MRSA. REF: 267 OBJ: Level 3: Synthesis 36. A patient undergoes a colon resection. Because of the amount of bacteria present in the colon, the physician put the patient on broad-spectrum antibiotics after surgery. The patient develops a fever 2 days after surgery. He developed an infection with vancomycin-resistant enterococci (VRE). What antibiotics can be used to treat this organism? a. Synercid b. Quinolones c. Aminoglycosides d. Erythromycin A In an attempt to avoid the overuse and subsequent emergence of resistance to vancomycin, vancomycin was used sparingly during its introduction. Unfortunately, this strategy did not prevent overuse and resulted in the emergence of vancomycin-resistant enterococci (VRE) isolates in health care settings. Currently, there are two choices for the treatment of VRE: Synercid or Linezolid. REF: 268 OBJ: Level 3: Synthesis 37. How does Staphylococcus aureus acquire resistance to methicillin? a. An enzyme alteration b. Mobile DNA element c. Frameshift mutation d. RNA porin B Methicillin-resistant S. aureus (MRSA) emerged soon after its introduction into clinical medicine in the 1960s and now exemplifies the acquisition of a new target by a pathogen to solve exposure to the toxic effects of the antibiotic. S. aureus solved the antimicrobial activity of methicillin exposure by acquisition of a mobile DNA element carrying a staphylococcal cassette chromosome mec (SCCmec), which confers resistance to methicillin. REF: 268 OBJ: Level 1: Recall 38. What is one of the first resistance mechanisms identified and is a strategy that bacteria use successfully to survive the action of many classes of antibiotics? a. Frameshift mutation b. Plasmid DNA acquisition c. Acquisition of inactivating enzymes d. Impermeability to the cell wall C The acquisition of enzymes that inactivate antibiotics directly is one of the first mechanisms of resistance identified in bacteria and is a strategy that bacteria use successfully to survive the action of many classes of antibiotics. Several of the best-studied classic examples are the enzymes that mediate hydrolysis of the -lactam ring of -lactam antibiotics. REF: 268 OBJ: Level 2: Interpretation 39. Extended -lactamases target all the following antibiotics except: a. penicillins. b. cephalosporins. c. monobactams. d. macrolides. D The extended-spectrum -lactamases (ESBLs) are now known to be derivatives of the common type -lactamases, but they differ by one or more amino acid substitutions near the reactive site of the enzyme. ESBLs have specific sets of penicillins, cephalosporins, and monobactams they can hydrolyze, and all ESBLs are not capable of hydrolyzing all cephalosporins equally well. REF: 268 OBJ: Level 1: Recall 40. Resistance to aminoglycosides is mediated by: a. efflux. b. changes in the target site. c. impermeability or by enzymatic modification of amino and hydroxy moieties appended to the cyclitol rings. d. all of the above. D Resistance to aminoglycosides is mediated by efflux, changes in target site, impermeability, or enzymatic modification of the amino and hydroxy moieties appended to the cyclitol rings. The most clinically relevant is enzymatic modification, which prevents recognition of the 16S binding sites and subsequent inhibition of mRNA translation. REF: 269 OBJ: Level 1: Recall 41. Plasmids are: a. circular structures present in bacteria that contain genes encoding proteins and RNA and have the capacity to self-replicate and portion into daughter cells during cellular division. b. DNA elements that encode transposition and excision function and can transpose from one place on the chromosome to another. c. genetic elements capable of integrating resistance genes (cassettes) by an integron-encoded, site-specific recombinase. d. DNA elements found in bacteria that carry genes only for the enzymes needed to promote their own transposition. A Plasmids are extrachromosomal DNA, circular structures present in bacteria that contain genes encoding proteins and RNA and have the capacity to self-replicate and partition into daughter cells during cellular division. Plasmids also acquire and exchange information with the chromosome and other host resident plasmids, including antibiotic resistance genes. REF: 270 OBJ: Level 1: Recall 42. Transposons are: a. circular structures present in bacteria that contain genes encoding proteins and RNA, and have the capacity to self-replicate and portion into daughter cells during cellular division. b. DNA elements that encode transposition and excision function and can transpose from one place on the chromosome to another. c. genetic elements capable of integrating resistance genes (cassettes) by an integron-encoded, site-specific recombinase. d. DNA elements found in bacteria that carry genes only for the enzymes needed to promote their own transposition. B Transposons (Tn) are DNA elements that encode transposition and excision functions and can transpose from one place on the chromosome or plasmid to another. Transposase, an enzyme that facilitates nonhomologous recombination, mediates the transposition event. Transposons are also capable of carrying antibiotic resistance genes and function as shuttles, carrying these determinants among plasmids and between plasmids and chromosomal DNA. REF: 270 OBJ: Level 1: Recall 43. Integrons are: a. circular structures present in bacteria that contain genes encoding proteins and RNA and have the capacity to self-replicate and portion into daughter cells during cellular division. b. DNA elements that encode transposition and excision function and can transpose from one place on the chromosome to another. c. genetic elements capable of integrating resistance genes (cassettes) by an integron-encoded, site-specific recombinase. d. DNA elements found in bacteria that carry genes only for the enzymes needed to promote their own transposition. C Integrons are genetic elements and have the capacity of integrating resistance genes by an integron-encoded, site-specific recombinase. The integron in Tn21 does not code for its own mobilization but can be moved when transposition proteins are provided in trans; is bound by imperfect terminal inverted repeats; contains the aadA1-resistant determinant on a cassette. REF: 271 OBJ: Level 1: Recall 44. Insertion sequences are: a. circular structures present in bacteria that contain genes encoding proteins and RNA, and the capacity to self-replicate and portion into daughter cells during cellular division. b. DNA elements that encode transposition and excision function, and can transpose from one place on the chromosome to another. c. genetic elements capable of integrating resistance genes (cassettes) by an integron-encoded, site-specific recombinase. d. DNA elements found in bacteria that carry genes only for the enzymes needed to promote their own transposition. D Insertion sequences are transposons found in bacteria that carry genes only for the enzymes needed to promote their own transposition. Insertion sequence elements can form composite transposable genetic elements, with the insertion elements forming the proximal and distal ends, and the genetic material that codes for antibiotic resistance located in-between. REF: 271 OBJ: Level 1: Recall [Show More]

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