Chapter 6 : Antibiotic Resistance and Survival in the Host

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Antibiotic Resistance and Survival in the Host, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555818111/9781555811747_Chap06-2.gif


The alarming increase in the number of multidrug-resistant microorganisms isolated in both clinical and nonclinical settings over the past decade parallels the rise in antibiotic use and exemplifies these adaptive abilities. Current antibiotic drugs target a variety of cellular processes and result in cell stasis or death through inhibition of protein, RNA or DNA synthesis, disruption of permeability barriers, or inhibition of cell wall peptidoglycan biosynthesis. Many drugs passively diffuse across the cytoplasmic membranes of both gram-positive and -negative bacteria. Bacteria possess certain intrinsic properties that provide natural resistance to some classes of antibiotics. Modifying or hydrolytic enzymes provide bacteria with a method of neutralizing certain drugs that have gained access to the cell. The nature of modern medicine dictates that, at some point, all pathogenic bacteria will encounter antimicrobials; thus, resistance will inevitably arise (possibly based on host-defense evasion mechanisms). Decreased exotoxin production may also contribute to the ability of these variants to evade host defenses and to their increased resistance to antibiotics in vivo. Biofilms are inherently resistant to both antibiotics and host defenses. Production of mature biofilms involves a complex regulatory pathway. Two-component regulatory systems provide bacteria with a way to integrate regulation of expression of virulence factors and antibiotic resistance into their general stress response pathways.

Citation: Macfarlane E, Hancock R. 2000. Antibiotic Resistance and Survival in the Host, p 93-104. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch6
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Schematic diagram summarizing the functions and interactions of the PhoP-PhoQ twocomponent regulatory system in serovar Typhimurium.

Citation: Macfarlane E, Hancock R. 2000. Antibiotic Resistance and Survival in the Host, p 93-104. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Amabile-Cuevas, C. F.,, and M. Cardenas- Garcia,. 1996. Antibiotic resistance: merely the tip of the iceberg of plasmid-driven bacterial evolution, p. 35 56. In C. F. Amabile-Cuevas (ed.), Antibiotic Resistance: From Molecular Basics to Therapeutic Options. R. G. Londes Co., Austin, Tex.
2. Bajaj, V.,, R. L. Lucas,, C. Hwang,, and C. A. Lee. 1996. Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol. Microbiol. 22: 703 714.
3. Baker, S. J.,, J. S. Gunn,, and R. Morona. 1999. The Salmonella typhi melittin resistance gene pqaB affects intracellular growth in PMAdifferentiated U937 cells, polymyxin B resistance and lipopolysaccharide. Microbiology 145: 367 378.
4. Balwit, J. M.,, P. van Langervelde,, J. M. Vann,, and R. A. Proctor. 1994. Gentamicin resistant menadione and hemin auxotrophic Staphylococcus aureus persist within cultured epithelial cells. J. Infect. Dis. 170: 1033 1037.
5. Bayer, A. S.,, D. C. Norman,, and K. S. Kim. 1987. Characterization of impermeability variants of Pseudomonas aeruginosa isolated during unsuccessful therapy of experimental endocarditis. Antimicrob. Agents Chemother. 31: 70 75.
6. Bearson, B.,, L. Wilson,, and J. W. Foster. 1998. A low pH-inducible, PhoPQ-dependent acid tolerance response protects Salmonella typhimurium against inorganic stress. J. Bacteriol. 180: 2409 2417.
7. Behlau, I.,, and S. I. Miller. 1993. A PhoPrepressed gene promotes Salmonella typhimurium invasion of epithelial cells. J. Bacteriol. 175: 4475 4484.
8. Bennett, P. M.,, and A. H. Linton. 1986. Do plasmids influence the survival of bacteria? J. Antimicrob. Chemother. 18( Suppl C): 123 126.
9. Björkman, J.,, D. Hughes,, and D. I. Andersson. 1998. Virulence of antibiotic-resistant Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 95: 3949 3953.
10. Brown, M. R. W.,, and J. Melling. 1969. Role of divalent cations in the action of polymyxin B and EDTA on Pseudomonas aeruginosa. J. Gen. Microbiol. 59: 263 271.
11. Bryan, L. E.,, A. J. Godfrey,, and T. Schollardt. 1985. Virulence of Pseudomonas aeruginosa strains with mechanisms of microbial persistence for β-lactam and aminoglycoside antibiotics in a mouse infection model. Can. J. Microbiol. 31: 377 380.
12. Bush, K.,, G. A. Jacoby,, and A. A. Medeiros. 1995. A functional classification scheme for betalactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39: 1211 1233.
13. Chopra, I. 1998. Over-expression of target genes as a mechanism of antibiotic resistance in bacteria. J. Antimicrob. Chemother. 41: 584 588.
14. Costerton, J. W.,, P. S. Stewart,, and E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284: 1318 1322.
15. Davies, J. E. 1997. Origins, acquisition and dissemination of antibiotic resistance determinants. Ciba Found. Symp. 207: 15 27.
16. Fields, P. I.,, E. A. Groisman,, and F. Heffron. 1989. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science 243: 1059 1062.
17. Fralick, J. A. 1996. Evidence that TolC is required for the functioning of the Mar/AcrAB efflux pump of Escherichia coli. J. Bacteriol. 178: 5803 5805.
18. Govan, J. R. W.,, and V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60: 539 574.
19. Groisman, E. A.,, E. Chiao,, C. J. Lipps,, and F. Heffron. 1989. Salmonella typhimurium phoP virulence gene is a transcriptional regulator. Proc. Natl. Acad. Sci. USA 86: 7077 7081.
20. Groisman, E. A.,, F. Heffron,, and F. Soloman. 1992. Molecular genetic analysis of the Escherichia coli phoP locus. J. Bacteriol. 174: 486 491.
21. Groisman, E. A.,, J. Kayser,, and F. C. Soncini. 1997. Regulation of polymyxin resistance and adaptation to low-Mg2_ environments. J. Bacteriol. 179: 7040 7045.
22. Gunn, J. S.,, and S. I. Miller. 1996. PhoPPhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J. Bacteriol. 178: 6857 6864.
23. Gunn, J. S.,, K. B. Lim,, J. Krueger,, K. Kim,, L. Guo,, M. Hackett,, and S. I. Miller. 1998. PmrA-PmrB-regulated genes necessary for 4- aminoarabinose modification and polymyxin B resistance. Mol. Microbiol. 27: 1171 1182.
24. Hachler, H.,, P. Santarnam,, and F. H. Kayser. 1996. Sequence and characterization of a novel chromosomal aminoglycoside phosphotransferase gene aph( 3')- IIb in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 40: 1254 1256.
25. Hall, M. N.,, and T. J. Sihavy. 1981. Genetic analysis of the ompB locus in Escherichia coli K-12. J. Mol. Biol. 151: 1 15.
26. Hall, R. M.,, and C. M. Collis. 1995. Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination. Mol. Microbiol. 15: 593 600.
27. Hancock, R. E. W., 1994. Bacterial transport as an import mechanism and target for antimicrobials, p. 289 306. In N. H. Georgopapadakou (ed.), Drug Transport in Antimicrobial and Anticancer Chemotherapy. Marcel Dekker Inc., New York, N.Y.
28. Hancock, R. E. W.,, and A. Bell. 1988. Antibiotic uptake in Gram negative bacteria. Eur. J. Microbiol. Infect. Dis. 7: 713 720.
29. Hancock, R. E. W.,, and R. Lehrer. 1998. Cationic peptides: a new source of antibiotics. TIBTECH 16: 82 88.
30. Hëlander, I. M.,, I. Kilpeläinen,, and M. Vaara. 1994. Increased substitution of phosphate groups in lipopolysaccharides and lipid A of the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study. Mol. Microbiol. 11: 481 487.
31. Hoch, J. A. 1993. The phosphorelay signal transduction pathway in the initiation of Bacillus subtilis sporulation. J. Cell Biochem. 51: 55 61.
32. Johnston, C.,, D. A. Pegues,, C. J. Hueck,, C. A. Lee,, and S. I. Miller. 1996. Transcriptional activation of Salmonella typhimurium invasion genes by a member of the phosphorylated response-regulator superfamily. Mol. Microbiol. 22: 715 727.
33. Kasahara, M.,, A. Nakata,, and H. Shinagawa. 1992. Molecular analysis of the Escherichia coli phoP-phoQ operon. J. Bacteriol. 174: 492 498.
34. Klemperer, R. M. M.,, N. T. A. Ismail,, and M. R. W. Brown. 1979. Effect of R plasmid RP1 on the nutritional requirements of Escherichia coli in batch culture. J. Gen. Microbiol. 115: 325 331.
35. Latifi, A.,, M. Foglino,, K. Tanaka,, P. Williams,, and A. Lazdunski. 1996. A hierarchical quorum-sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhlR (VsmR) to the expression of the stationary phase sigma factor RpoS. Mol. Microbiol. 21: 1137 1146.
36. Ma, D.,, D. N. Cook,, M. Alberti,, N. G. Pon,, H. Nikaido,, and J. E. Hearst. 1993. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J. Bacteriol. 175: 6299 6313.
37. Macfarlane, E. L. A.,, A. Kwasnicka,, M. M. Ochs,, and R. E. W. Hancock. 1999. PhoPPhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol. Microbiol. 34: 305 316.
38. Miller, S. I.,, A. M. Kukral,, and J. J. Mekalanos. 1989. A two-component regulatory system ( phoP phoQ) controls Salmonella typhimurium virulence. Proc. Natl. Acad. Sci. USA 86: 5054 5058.
39. Miller, S. I.,, and J. J. Mekalanos. 1990. Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J. Bacteriol. 172: 2485 2490.
40. Mills, D. M.,, V. Bajaj,, and C. A. Lee. 1995. A 40kB chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K- 12 chromosome. Mol. Microbiol. 15: 749 759.
41. Mizobuchi, S.,, J. Minami,, F. Jin,, O. Matsushita,, and A. Okabe. 1994. Comparison of the virulence of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Microbiol. Immunol. 38: 599 605.
42. Nakamura, H. 1968. Genetic determination of resistance to acriflavine, phenethyl alcohol, and sodium dodecyl sulfate in Escherichia coli. J. Bacteriol. 96: 987 996.
43. Nicas, T. I.,, and R. E. W. Hancock. 1980. Outer-membrane protein H1 of Pseudomonas aeruginosa: involvement in adaptive and mutational resistance to ethylenediaminetetraacetic acid, polymyxin B, and gentamicin. J. Bacteriol. 143: 872 878.
44. Nikaido, H. 1998. Antibiotic resistance caused by Gram negative multidrug efflux pumps. Clin. Infect. Dis. 27: S32 S41.
45. Nikaido, H.,, and D. G. Thanassi. 1993. Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples. Antimicrob. Agents Chemother. 37: 1393 1399.
46. O’Toole, G. A.,, and R. Kolter. 1998. Initiation of biofilm development in Pseudomonas fluorescens WCS365 proceeds via multiple convergent signaling pathways: a genetic analysis. Mol. Microbiol. 30: 295 299.
47. Paulsen, I. T.,, M. W. Brown,, and R. A. Skurray. 1996. Proton-dependent multidrug efflux systems. Microbiol. Rev. 60: 575 608.
48. Paulsen, I. T.,, R. A. Skurray,, R. Tam,, M. H. Saier, Jr.,, R. J. Turner,, J. H. Weiner,, E. B. Goldberg,, and L. L. Grinius. 1996. The SMR family: a novel family of multidrug efflux proteins involved with the efflux of lipophilic drugs. Mol. Microbiol. 19: 1167 1175.
49. Piers, K. L.,, M. H. Brown,, and R. E. W. Hancock. 1994. Improvement of outer membrane-permeabilizing and lipopolysaccharide- binding activities of an antimicrobial cationic peptide by C-terminal modification. Antimicrob. Agents Chemother. 38: 2311 2316.
50. Poole, K.,, K. Krebes,, C. McNally,, and S. Neshat. 1993. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J. Bacteriol. 175: 7363 7372.
51. Proctor, R. A.,, B. Kahl,, C. von Eiff,, P. E. Vandaux,, D. P. Lew,, and G. Peters. 1998. Staphylococcal small colony variants have novel mechanisms for antibiotic resistance. Clin. Infect. Dis. 27( Suppl 1): S68 S74.
52. Proctor, R. A.,, J. M. Balwit,, and O. Vesga. 1994. Variant populations of Staphylococcus aureus can cause persistent and recurrent infections. Infect. Agents Dis. 3: 302 312.
53. Reimmann, C.,, M. Beyeler,, A. Latifi,, H. Winteler,, M. Foglino,, A. Lazdunski,, and D. Haas. 1997. The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyrylhomoserine lactone and the formation of virulence factors pyocyanin, cyanide, and lipase. Mol. Microbiol. 24: 309 319.
54. Salyers, A. A.,, and C. F. Amabile-Cuevas. 1997. Why are antibiotic resistance genes so resistant to elimination? Antimicrob. Agents Chemother. 41: 2321 2325.
55. Schurr, M. J.,, H. Yu,, J. C. Boucher,, N. S. Hibler,, and V. Deretic. 1995. Multiple promoters and induction by heat shock of the gene encoding the alternative sigma factor AlgU ( σ E) which controls mucoidy in cystic fibrosis isolates of Pseudomonas aeruginosa. J. Bacteriol. 177: 5670 5679.
56. Shaw, K. J.,, P. N. Rather,, R. S. Hare,, and G. H. Miller. 1993. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol. Rev. 57: 138 163.
57. Silva, J. C.,, A. Haldimann,, M. K. Prahalad,, C. T. Walsh,, and B. L. Wanner. 1998. In vivo characterization of the type A and B vancomycinresistant enterococci (VRE) VanRS twocomponent systems in Escherichia coli: a nonpathogenic model for studying the VRE signal transduction pathways. Proc. Natl. Acad. Sci. USA 95: 11951 11956.
58. Soncini, F. C.,, and E. A. Groisman. 1996. Two-component regulatory systems can interact to process multiple environmental signals. J. Bacteriol. 178: 6796 6801.
59. Soncini, F. C.,, E. G. Véscovi,, and E. A. Groisman. 1995. Transcriptional autoregulation of the Salmonella typhimurium phoPQ operon. J. Bacteriol. 177: 4364 4371.
60. Soncini, F. C.,, E. G. Véscovi,, F. Soloman,, and E. A. Groisman. 1996. Molecular basis of the magnesium deprivation response in Salmonella typhimurium: identification of PhoP-regulated genes. J. Bacteriol. 178: 5092 5099.
61. Spratt, B. G. 1996. Antibiotic resistance: counting the cost. Curr. Biol. 6: 1219 1221.
62. Summers, A. O.,, J. Wireman,, M. J. Vimy,, F. L. Lorsheider,, B. Marshall,, S. B. Levy,, S. Bennet,, and L. Billard. 1993. Mercury released from dental ‘‘silver’’ fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates. Antimicrob. Agents Chemother. 37: 825 834.
63. Tomasz, A.,, A. Albino,, and E. Zanati. 1970. Multiple antibiotic resistance in a bacterium with suppressed autolytic systems. Nature 227: 138 140.
64. Véscovi, E. G.,, F. C. Soncini,, and E. A. Groisman. 1996. Mg 2+ as an extracellular signal: environmental regulation of Salmonella virulence. Cell 84: 165 174.
65. Vesga, O.,, M. C. Groeschel,, M. F. Otten,, D. W. Brar,, J. M. Vann,, and R. A. Proctor. 1996. Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J. Infect. Dis. 173: 739 742.
66. Whistler, C. A.,, N. A. Corbell,, A. Sarniguet,, W. Ream,, and J. E. Loper. 1998. The two-component regulators GacS and GacA influence accumulation of the stationary phase sigma factor σ S and the stress response in Pseudomonas fluorescens Pf-5. J. Bacteriol. 180: 6635 6641.
67. Wright, G. D.,, and P. R. Thompson. 1999. Aminoglycoside phosphotransferases: proteins, structure, and mechanism. Frontiers Biosci. 9: d9 d21.
68. Ziha-Zarifi, I.,, C. Llanes,, T. Köhler,, J.-C. Pechere,, and P. Plesiat. 1999. In vivo emergence of multidrug resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob. Agents Chemother. 43: 287 291.


Generic image for table

Major classes of antibiotics in current medical use

Citation: Macfarlane E, Hancock R. 2000. Antibiotic Resistance and Survival in the Host, p 93-104. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch6

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error