Chapter 23 : Bacterial Persistence: Strategies for Survival

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

Preview this chapter:
Zoom in

Bacterial Persistence: Strategies for Survival, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817978/9781555812140_Chap23-1.gif /docserver/preview/fulltext/10.1128/9781555817978/9781555812140_Chap23-2.gif


This chapter focuses on a few organisms as paradigms of persistence strategies. Programmed rearrangement of genes encoding surface antigens (antigenic variation) is essential for the evasion of adaptive humoral immunity by extracellular, blood-borne pathogens such as the spp. that cause relapsing fever (RF) and Lyme disease (LD). Gonorrhea, caused by the gram-negative diplococcus , is one of the most prevalent sexually transmitted diseases of humans-every year, one million new cases are reported in the United States alone. Variation of several cell surface components of the gonococcus-notably, the pili, outer membrane Opa proteins, and LOS-is controlled by distinct and complex mechanisms. Despite the manifest importance of persistence in the pathogenesis of tuberculosis (TB), little is known about the mechanisms that promote mycobacterial persistence in vivo. Indeed, reactive oxygen intermediates (ROI) detoxification mediated by the KatG catalase is essential for bacterial persistence in mice following induction of adaptive immunity. One of the most familiar and complex types of medically relevant biofilm is dental plaque, comprising hundreds of microbial species. The study of microbial biofilms and their role in persistent infections is still at an early stage. The environmental signals that promote biofilm formation and dissolution and the signals that the bacteria use to communicate with each other are just beginning to be deciphered.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23

Key Concept Ranking

Bacterial Proteins
Major Histocompatibility Complex Class II
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Contrasting epidemic dynamics of measles and TB. (A) Numerical simulation of a measles epidemic initiated by entering one infectious case at time zero into a susceptible population of 500,000. The simulation illustrates successive epidemic waves at roughly 6- to 12-month intervals. Redrawn from with permission of the American Association for the Advancement of Science. (B) Numerical simulation of a tuberculosis epidemic initiated by entering one infectious case at time zero into a population of 200,000. The simulation illustrates the relative contribution of three types of disease to the overall incidence: fast (progressive primary), slow (postprimary), and relapse tuberculosis. A fourth type, exogenous reinfection, is not included in the model but would presumably increase the peak level and duration of the epidemic. Redrawn from with permission of the publisher. The contrasting epidemic dynamics of measles and tuberculosis are also reflected in the CCS required for endemicity, which is roughly 250,000 for measles ( ) and 500 or less for tuberculosis ( ).

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

spirochetes visible as long, slender, spiral threads in a dermal syphilis lesion. Warthin-Starry stain. Magnification, ×695. Reprinted from with permission of the publisher.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Stages of the multistage disease syphilis. (A) Primary syphilis. Chancre of the palm. The primary chancre most often occurs on the genitalia, but extragenital chancres are not rare. Without treatment, the chancre usually heals in 1 to 4 weeks. (B) Secondary syphilis. Generalized papulosquamous lesions. (C) Tertiary syphilis. Gummas of the leg. Ulcerative gummas can occur in multiple organ systems. The onset is usually 5 to 20 years after the primary stage. (D) Gumma of tertiary syphilis. A central region of caseation necrosis is surrounded by an epithelioid granulomatous reaction (including multinucleated giant cells) and peripheral fibrosis. H&E stain. Magnification, ×126. Panels A to C reprinted from with permission of the publisher; panel D reprinted from with permission of the publisher.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Relapsing fever. Spikes of fever are accompanied by waves of spirochetemia. In each successive wave, a new antigenic variant dominates (indicated by different shapes). As the bacteria are cleared by the specific humoral response, the fever subsides. However, expansion of a newly emergent variant brings about another febrile episode within a few days. Reviewed by .

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5.
Figure 5.

Antigenic and phase variation of pili in . (A) Antigenic variation. Pilin is encoded by one or two expression loci. Variant pilin sequences are stored in silent cassettes, which lack the 5′ coding and promoter sequences required for expression. Nonreciprocal recombination between and sequences gives rise to expression of variant pilin subunits. Modular recombination can generate mosaic loci containing sequences derived from several distinct loci. (B) Phase variation. PilC is a minor subunit that is required for proper assembly and export of pili. A run of G residues near the 5′ end of the gene can vary in length due to slipped-strand DNA synthesis during chromosome replication. Depending on the exact number of G residues, the downstream coding sequences may be in or out of frame for translation.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.
Figure 6.

Chest X-ray of a 70-year-old woman shortly before her death. “A white woman had cavitary tuberculosis of 41 years' duration. She had bilateral bronchiectasis, cavitation of the right upper lobe, a collapsed left lung, pleural effusion, and an induced left pneumothorax of 36 years' duration. She had received no antituberculous drugs for 28 years from the onset of her illness, and these drugs, when finally prescribed, were taken inadequately. Pleural effusion present for 28 years required aspiration. recovered by culture of sputum was resistant to all antituberculous drugs except streptomycin (which the patient had never received due to allergy).” Reprinted from , with permission of the American Lung Association.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7.
Figure 7.

The treated pulmonary lesion and its tubercle bacillus: death and resurrection. Resected lung lesions from patients on chemotherapy were cultured. “Open” and active cavitary lesions, with patent connections to the airways, yielded drugresistant tubercle bacilli in the normal time frame (less than 2 months of incubation). “Closed” and dormant encapsulated lesions, with no apparent connections to an airway, yielded drug-sensitive tubercle bacilli only after extended incubation (3 to 10 months). Derived from .

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8.
Figure 8.

Biofilm biogenesis. Planktonic bacteria swim to a surface via flagellar motility and attach (mediated by flagella and nutrient sensing mechanisms). Replication on the surface leads to the formation of a monolayer of cells, which aggregate by twitching motility (mediated by type IV pili) and adhere to each other, forming surface-attached microcolonies. These microcolonies become embedded within a thick layer of secreted EPS. As the cell density increases, quorum sensing via HSLs synthesized by LasI triggers the developmental changes required for formation of the correct architecture and thickness of the fully mature biofilm. The mature biofilm is penetrated by fluid-filled channels that deliver nutrients and remove wastes. Bacteria within the biofilm are protected from destruction by antibodies, phagocytes, and antimicrobials. The steps leading to dissociation of biofilms and reversion to the planktonic form are poorly understood but may involve environmental sensing and programmed disruption or simple physical forces such as shear stress from fluid flow. Redrawn from with permission of the American Association for the Advancement of Science.

Citation: Muñoz-Elías E, McKinney J. 2002. Bacterial Persistence: Strategies for Survival, p 331-355. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch23
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Aderem, A.,, and D. M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Ann. Rev. Immunol. 17:593623.
2. Akins, D. R.,, E. Robinson,, D. Shevchenko,, C. Elkins,, D. L. Cox,, and J. D. Radolf. 1997. Tromp1, a putative rare outer membrane protein, is anchored by an uncleaved signal sequence to the Treponema pallidum cytoplasmic membrane. J. Bacteriol. 179:50765086.
3. Alder, J. D.,, L. Friess,, M. Tengowski,, and R. F. Schell. 1990. Phagocytosis of opsonized Treponema pallidum subsp. pallidum proceeds slowly. Infect. Immun. 58:11671173.
4. Arroll, T. W.,, A. Centurion-Lara,, S. A. Lukehart,, and W. C. Van Voorhis. 1999. T-cell responses to Treponema pallidum subsp. pallidum antigens during the course of experimental syphilis infection. Infect. Immun. 67:47574763.
5. Baker-Zander, S. A.,, E. W. Hook,, P. Bonin,, H. H. Handsfield,, and S. A. Lukehart. 1985. Antigens of Treponema pallidum recognized by IgG and IgM antibodies during syphilis in humans. J. Infect. Dis. 151:264272.
6. Baker-Zander, S. A.,, M. J. Fohn,, and S. A. Lukehart. 1988. Development of cellular immunity to individual soluble antigens of Treponema pallidum during experimental syphilis. J. Immunol. 141:43634369.
7. Baker-Zander, S. A.,, and S. A. Lukehart. 1992. Macrophage-mediated killing of opsonized Treponema pallidum. J. Infect. Dis. 165:6974.
8. Baker-Zander, S. A.,, J. M. Shaffer,, and S. A. Lukehart. 1993. Characterization of the serum requirement for macrophage-mediated killing of Treponema pallidum ssp. pallidum: relationship to the development of opsonizing antibodies. FEMS Immunol. Med. Microbiol. 6:273279.
9. Barbour, A. G. 1990. Antigenic variation of a relapsing fever Borrelia species. Annu. Rev. Microbiol. 44:155171.
10. Barbour, A. G.,, S. L. Tessier,, and H. G. Stoenner. 1982. Variable major proteins of Borrellia hermsii. J. Exp. Med. 156:13121324.
11. Barbour, A. G.,, and S. F. Hayes. 1986. Biology of Borrelia species. Microbiol. Rev. 50:381400.
12. Barclay, W. R.,, R. H. Ebert,, G. V. Le Roy,, R. W. Manthei,, and L. J. Roth. 1953. Distribution and excretion of radioactive isoniazid in tuberculosis patients. JAMA 151:13841388.
13. Barthold, S. W. 1993. Antigenic stability of Borrelia burgdorferi during chronic infections of immunocompetent mice. Infect. Immun. 61:49554961.
14. Barthold, S. W., 2000. Lyme borreliosis, p. 281304. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
15. Barthold, S. W.,, M. S. de Souza,, J. L. Janotka,, A. L. Smith,, and D. H. Persing. 1993. Chronic Lyme borreliosis in the laboratory mouse. Am. J. Pathol. 143:959971.
16. Bassler, B. L. 1999. How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr. Opin. Microbiol. 2:582587.
17. Bishop, N. H.,, and J. N. Miller. 1976a. Humoral immunity in experimental syphilis. I. The demonstration of resistance conferred by passive immunization. J. Immunol. 117:191196.
18. Bishop, N. H.,, and J. N. Miller. 1976b. Humoral immunity in experimental syphilis. II. The relationship of neutralizing factors in immune serum to acquired resistance. J. Immunol. 117:197 207.
19. Bjerknes, R.,, H. K. Guttormsen,, C. O. Solberg,, and L. M. Wetzler. 1995. Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst. Infect. Immun. 63:160167.
20. Black, F. L. 1966. Measles endemicity in insular populations: critical community size and its evolutionary implications. J. Theor. Biol. 11:207211.
21. Black, F. L. 1975. Infectious diseases in primitive societies. Science 187:515518.
22. Black, F. L.,, W. J. Hierholzer,, F. D. Pinheiro,, A. S. Evans,, J. P. Woodall,, E. M. Opton,, J. E. Emmons,, B. S. West,, G. Edsall,, W. G. Downs,, and G. D. Wallace. 1974. Evidence for persistence of infectious agents in isolated human populations. Am. J. Epidemiol. 100:230250.
23. Blanco, D. R.,, J. N. Miller,, and P. A. Hanff. 1984. Humoral immunity in experimental syphilis: the demonstration of IgG as a treponemicidal factor in immune rabbit serum. J. Immunol. 133: 26932697.
24. Blanco, D. R.,, J. N. Miller,, and M. A. Lovett. 1997. Surface antigens of the syphilis spirochete and their potential as virulence determinants. Emerg. Infect. Dis. 3:1120.
25. Bloomquist, C. G.,, and W. F. Liljemark,. 2000. Dental plaque, p. 409421. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham- Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
26. Blower, S. M.,, A. R. McLean,, T. C. Porco,, P. M. Small,, P. C. Hopewell,, M. A. Sanchez,, and A. R. Moss. 1995. The intrinsic transmission dynamics of tuberculosis epidemics. Nat. Med. 1:815821.
27. Borst, P.,, and D. R. Greaves. 1987. Programmed gene rearrangements altering gene expression. Science 235:658667.
28. Brooks, G. F.,, and C. J. Lammel. 1989. Humoral immune response to gonococcal infections. Clin. Microbiol. Rev. 2(Suppl.):S5S10.
29. Brown, C. R.,, and S. L. Reiner. 1999. Experimental lyme arthritis in the absence of interleukin-4 or gamma interferon. Infect. Immun. 67:33293333.
30. Cadavid, D.,, P. M. Pennington,, T. A. Kerentseva,, S. Bergstrom,, and A. G. Barbour. 1997. Immunologic and genetic analyses of VmpA of a neurotropic strain of Borrelia turicatae. Infect. Immun. 65:33523360.
31. Cadavid, D.,, D. D. Thomas,, R. Crawley,, and A. G. Barbour. 1994. Variability of a bacterial surface protein and disease expression in a possible mouse model of systemic Lyme borreliosis. J. Exp. Med. 179:631642.
32. Centers for Disease Control and Prevention. 1991. Primary and secondary syphilis—United States, 1981-1990. Morb. Mortal. Wkly. Rep. 40:314315, 321323.
33. Centers for Disease Control and Prevention. 1999. Primary and secondary syphilis—United States, 1998. Morb. Mortal. Wkly. Rep. 48:873878.
34. Centurion-Lara, A.,, C. Castro,, L. Barrett,, C. Cameron,, M. Mostowfi,, W. C. Van Voorhis,, and S. A. Lukehart,, S.A. 1999. Treponema pallidum major sheath protein homologue TprK is a target of opsonic antibody and the protective immune response. J. Exp. Med. 189:647656.
35. Centurion-Lara, A.,, C. Godornes,, C. Castro,, W. C. Van Voorhis,, and S. A. Lukehart. 2000. The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles. Infect. Immun. 68:824831.
36. Chan, J.,, and J. L. Flynn,. 1999. Nitric oxide in Mycobacterium tuberculosis infection. In F. C. Fang (ed.), Nitric Oxide and Infection. Kluwer Academic/Plenum Publishers, New York, N.Y..
37. Comstock, G. W.,, V. T. Livesay,, and S. F. Woolpert. 1974. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am. J. Epidemiol. 99:131138.
38. Costerton, J. W.,, Z. Lewandowski,, D. E. Caldwell,, D. R. Korber,, and H. M. Lappin-Scott. 1995. Microbial biofilms. Annu. Rev. Microbiol. 49:711745.
39. Costerton, J. W.,, and P. S. Stewart,. 2000. Biofilms and device-related infections, p. 423439. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
40. Costerton, J. W.,, P. S. Stewart,, and E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284:13181322.
41. Cox, D. L.,, P. Chang,, A. W. McDowall,, and J. D. Radolf. 1992. The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infect. Immun. 60: 10761083.
42. Crawford, C.,, J. S. Knapp,, J. Hale,, and K. K. Holmes. 1977. Asymptomatic gonorrhea in men: caused by gonococci with unique nutritional requirements. Science 196:13521353.
43. Cucurull, E.,, and L. R. Espinoza. 1998. Gonococcal arthritis. Rheum. Dis. Clin. North Am. 24:305322.
44. Danaher, R. J.,, J. C. Levin,, D. Arking,, C. L. Burch,, R. Sandlin,, and D. C. Stein. 1995. Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation. J. Bacteriol. 177:72757279.
45. Daniel, T. M.,, J. H. Bates,, and K. A. Downes,. 1994. History of tuberculosis, p. 1324. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection, and Control. ASM Press, Washington, D.C..
46. Dannenberg, A. M., Jr.,, and G. A. W. Rook. 1994. Pathogenesis of pulmonary tuberculosis: an interplay of tissue-damaging and macrophage-activating immune responses—dual mechanisms that control bacillary multiplication, p. 459483. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection, and Control. ASM Press, Washingon, D.C..
47. Das, S.,, S. W. Barthold,, S. S. Giles,, R. R. Montgomery,, S. R. Telford III,, and E. Fikrig. 1997. Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. J. Clin. Investig. 99:987995.
48. Davies, D. G.,, M. R. Parsek,, J. P. Pearson,, B. H. Iglewski,, J. W. Costerton,, and E. P. Greenberg. 1998. The involvement of cell-to- cell signals in the development of a bacterial biofilm. Science 280:295298.
49. Dehio, C.,, S. D. Gray-Owen,, and T. F. Meyer. 1998. The role of neisserial Opa proteins in interactions with host cells. Trends Microbiol. 6:489495.
50. Dehio, C.,, S. D. Gray-Owen,, and T. F. Meyer. 2000. Host cell invasion by pathogenic Neisseriae. Subcell. Biochem. 33:6196.
51. Deitsch, K. W.,, E. R. Moxon,, and T. E. Wellems. 1997. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections. Microbiol. Mol. Biol. Rev. 61:281293.
52. Deretic, V., 2000. Pseudomonas aeruginosa infections, p. 305326. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
53. de Silva, A. M.,, and E. Fikrig. 1997. Arthropod- and host-specific gene expression by Borrelia burgdorferi. J. Clin. Investig. 99: 377379.
54. de Silva, A. M.,, E. Fikrig,, E. Hodzic,, F. S. Kantor,, S. R. Telford III,, and S. W. Barthold. 1998. Immune evasion by tickborne and host-adapted Borrelia burgdorferi. J. Infect. Dis. 177:395 400.
55. de Silva, A. M.,, S. R. Telford III,, L. R. Brunet,, S. W. Barthold,, and E. Fikrig. 1996. Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. J. Exp. Med. 183:271275.
56. Drake, D.,, and T. C. Montie. 1988. Flagella, motility and invasive virulence of Pseudomonas aeruginosa. J. Gen. Microbiol. 134: 4352.
57. Dubois, A.,, A. Welch,, D. E. Berg,, and M. J. Blaser,. 2000. Helicobacter pylori, p. 263280. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
58. Dutta, U.,, P. K. Garg,, R. Kumar,, and R. K. Tandon. 2000. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am. J. Gastroenterol. 95: 784787.
59. Dye, C.,, S. Scheele,, P. Dolin,, V. Pathania,, and M. C. Raviglione. 1999. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. JAMA 282:677686.
60. Edwards, W. M.,, R. S. Cox, Jr., J. P. Cooney, and R. I. Crone. 1970. Active pulmonary tuberculosis with cavitation of forty-one years’ duration. Am. Rev. Respir. Dis. 102:448455.
61. Egan, P. J.,, and S. R. Carding,. 2000. Influence of γδ T cells on the development of chronic disease and persistent bacterial infections, p. 165182. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham- Rundles (ed.), Persistent Bacterial Infections, ASM Press, Washington, D.C..
62. Eng, R. H.,, F. T. Padberg,, S. M. Smith,,, E. N. Tan,, and C. E. Cherubin. 1991. Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria. Antimicrob. Agents Chemother. 35:18241828.
63. Ernst, J. D. 1998. Macrophage receptors for Mycobacterium tuberculosis. Infect. Immun. 66:12771281.
64. Evans, D. J.,, D. G. Allison,, M. R. Brown,, and P. Gilbert. 1991. Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate. J. Antimicrob. Chemother. 27:177184.
65. Evans, J. 1999. Lyme disease. Curr. Opin. Rheumatol. 11:281288.
66. Feldman, M.,, R. Bryan,, S. Rajan,, L. Scheffler,, S. Brunnert,, H. Tang,, and A. Prince. 1998. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect. Immun. 66:4351.
67. Fenner, F.,, and B. Fantini. 1999. Biological Control of Vertebrate Pests: The History of Myxomatosis—an Experiment in Evolution, CABI Publishing, New York, N.Y. .
68. Ferrari, G.,, H. Langen,, M. Naito,, and J. Pieters. 1999. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 97:435447.
69. Figueroa, J. E.,, and P. Densen. 1991. Infectious diseases associated with complement deficiencies. Clin. Microbiol. Rev. 4:359395.
70. Fikrig, E.,, L. K. Bockenstedt,, S. W. Barthold,, M. Chen,, H. Tao,, P. Ali-Salaam,, S. R. Telford,, and R. A. Flavell. 1994. Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis. J. Infect. Dis. 169:568574.
71. Fikrig, E.,, M. Chen,, S. W. Barthold,, J. Anguita,, W. Feng,, S. R. Telford, III, and R. A. Flavell. 1999. Borrelia burgdorferi erpT expression in the arthropod vector and murine host. Mol. Microbiol. 31:281290.
72. Fikrig, E.,, H. Tao,, F. S. Kantor,, S. W. Barthold,, and R. A. Flavell. 1993. Evasion of protective immunity by Borrelia burgdorferi by truncation of outer surface protein B. Proc. Natl. Acad. Sci. USA 90:40924096.
73. Fitzgerald, T. J. 1981. Pathogenesis and immunology of Treponema pallidum. Annu. Rev. Microbiol. 35:2954.
74. Fitzgerald, T. J.,, L. A. Repesh,, D. R. Blanco,, and J. N. Miller. 1984. Attachment of Treponema pallidum to fibronectin, laminin, collagen IV, and collagen I, and blockage of attachment by immune rabbit IgG. Br. J. Vener. Dis. 60:357363.
75. Foster, J. W. 1995. Low pH adaptation and the acid tolerance response of Salmonella typhimurium. Crit. Rev. Microbiol. 21: 215237.
76. Fraser, C. M.,, S. Casjens,, W. M. Huang,, G. G. Sutton,, R. Clayton,, R. Lathigra,, O. White,, K. A. Ketchum,, R. Dodson,, E. K. Hickey,, M. Gwinn,, B. Dougherty,, J. F. Tomb,, R. D. Fleischmann,, D. Richardson,, J. Peterson,, A. R. Kerlavage,, J. Quackenbush,, S. Salzberg,, M. Hanson,, R. van Vugt,, N. Palmer,, M. D. Adams,, J. Gocayne,, J. C. Venter, et al. 1997. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390:580586.
77. Fraser, C. M.,, S. J. Norris,, G. M. Weinstock,, O. White,, G. G. Sutton,, R. Dodson,, M. Gwinn,, E. K. Hickey,, R. Clayton,, K. A. Ketchum,, E. Sodergren,, J. M. Hardham,, M. P. McLeod,, S. Salzberg,, J. Peterson,, H. Khalak,, D. Richardson,, J. K. Howell,, M. Chidambaram,, T. Utterback,, L. McDonald,, P. Artiach,, C. Bowman,, M. D. Cotton,, J. C. Venter, et al. 1998. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281:375388.
78. Fratazzi, C.,, R. D. Arbeit,, C. Carini,, M. K. Balcewicz-Sablinska,, J. Keane,, H. Kornfeld,, and H. G. Remold. 1999. Macrophage apoptosis in mycobacterial infections. J. Leukoc. Biol. 66:763764.
79. Fu, Y.,, and J. E. Galan. 1999. A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401:293297.
80. Galan, J. E.,, and A. Collmer. 1999. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284: 13221328.
81. Garay, S. M., 1996. Tuberculosis and the human immunodeficiency virus infection, p. 443465. In W. N. Rom,, and S. Garay (ed.), Tuberculosis. Little, Brown & Co., Boston, Mass..
82. Gatfield, J.,, and J. Pieters. 2000. Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288:16471650.
83. Gern, L.,, and P. F. Humair. 1998. Natural history of Borrelia burgdorferi sensu lato. Wien. Klin. Wochenschr. 110:856858.
84. Ghinsberg, R. C.,, and Y. Nitzan. 1992. Is syphilis an incurable disease? Med. Hypotheses 39:3540.
85. Gibbs, C. P.,, B. Y. Reimann,, E. Schultz,, A. Kaufmann,, R. Haas,, and T. F. Meyer. 1989. Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms. Nature 338: 651652.
86. Gilbert, P.,, P. J. Collier,, and M. P. Brown. 1990. Influence of growth rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy, and stringent response. Antimicrob. Agents Chemother. 34:18651868.
87. Gilman, R. H. 1989. General considerations in the management of typhoid fever and dysentery. Scand. J. Gastroenterol. Suppl. 169:1118.
88. Gjestland, T. 1955. The Oslo study of untreated syphilis—an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. Acta Dermatol. Vener. 35(Suppl. 34):1368.
89. Glickman, M. S.,, J. S. Cox,, and W. R. Jacobs, Jr. 2000. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell 5:717727.
90. Gomes, M. S.,, S. Paul,, A. L. Moreira,, R. Appelberg,, M. Rabinovitch,, and G. Kaplan. 1999. Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages. Infect. Immun. 67:31993206.
91. Gotschlich, E. C. 1994. Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide. J. Exp. Med. 180:21812190.
92. Govan, J. R.,, and V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60:539574.
93. Graf, M. 1998. Quarantine: the Story of Typhoid Mary. Vantage Press, N.Y..
Grigg, E. R. N. 1958. The arcana of tuberculosis, with a brief epidemiologic history of the disease in the USA. Am. Rev. Tuberc. Pulm. Dis. 78:151172, 426-453., 583603.
95. Groisman, E. A.,, and H. Ochman. 1997. How Salmonella became a pathogen. Trends Microbiol. 5:343349.
96. Gylfe, A.,, S. Bergstrom,, J. Lundstrom,, and B. Olsen. 2000. Reactivation of Borrelia infection in birds. Nature 403:724725.
97. Haake, D. A.,, and M. A. Lovett,. 1990. Interjunctional invasion of endothelial monolayers by Treponema pallidum. p. 297315. In B. H. Iglewski,, and V. L. Clark (ed.), Molecular Basis of Bacterial Pathogenesis. Academic Press Inc., San Diego, Calif..
98. Haas, F.,, and S. S. Haas,. 1996. The origins of Mycobacterium tuberculosis and the notion of its contagiousness, p. 319. In W. N. Rom and S. Garay (ed.), Tuberculosis. Little, Brown & Co., Boston, Mass..
99. Hagblom, P.,, E. Segal,, E. Billyard,, and M. So. 1985. Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae. Nature 315:156158.
100. Handsfield, H. H.,, T. O. Lipman,, J. P. Harnisch,, E. Tronca,, and K. K. Holmes. 1974. Asymptomatic gonorrhea in men. Diagnosis, natural course, prevalence and significance. N. Engl. J. Med. 290:117123.
101. Hardt, W. D.,, L. M. Chen,, K. E. Schuebel,, X. R. Bustelo,, and J. E. Galan. 1998. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93:815826.
102. Hassett, D. J.,, J. F. Ma,, J. G. Elkins,, T. R. McDermott,, U. A. Ochsner,, S. E. West,, C. T. Huang,, J. Fredericks,, S. Burnett,, P. S. Stewart,, G. McFeters,, L. Passador,, and B. H. Iglewski. 1999. Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol. Microbiol. 34:10821093.
103. Hemmer, B.,, B. Gran,, Y. Zhao,, A. Marques,, J. Pascal,, A. Tzou,, T. Kondo,, I. Cortese,, B. Bielekova,, S. E. Straus,, H. F. Mc- Farland,, R. Houghten,, R. Simon,, C. Pinilla,, and R. Martin. 1999. Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat. Med. 5:13751382.
104. Herzog, C. 1976. Chemotherapy of typhoid fever: a review of the literature. Infection 4:166173.
105. Hessel, L.,, H. Debois,, M. Fletcher,, and R. Dumas. 1999. Experience with Salmonella typhi Vi capsular polysaccharide vaccine. Eur. J. Clin. Microbiol. Infect. Dis. 18:609620.
106. Hill, A. V. S. 1998. The immunogenetics of human infectious diseases. Annu. Rev. Immunol. 16:593617.
107. Hoge, C. W.,, L. Fisher,, H. D. Donnell, Jr.,, D. R. Dodson,, G. V. Tomlinson, Jr.,, R. F. Breiman,, A. B. Bloch,, and R. C. Good. 1994. Risk factors for transmission of Mycobacterium tuberculosis in a primary school outbreak: lack of racial difference in susceptibility to infection. Am. J. Epidemiol. 139:520530.
108. Hopper, S.,, B. Vasquez,, A. Merz,, S. Clary,, J. S. Wilbur,, and M. So. 2000. Effects of the immunoglobulin A1 protease on Neisseria gonorrhoeae trafficking across polarized T84 epithelial monolayers. Infect. Immun. 68:906911.
109. Hornick, R. B. 1985. Selective primary health care: strategies for control of disease in the developing world. XX. Typhoid fever. Rev. Infect. Dis. 7:536546.
110. Hornick, R. B.,, S. E. Greisman,, T. E. Woodward,, H. L. DuPont,, A. T. Dawkins,, and M. J. Snyder. 1970. Typhoid fever: pathogenesis and immunologic control. N. Engl. J. Med. 283:739 746.
111. Hu, L. T.,, and M. S. Klempner. 1997. Host-pathogen interactions in the immunopathogenesis of Lyme disease. J. Clin. Immunol. 17:354365.
112. Ilver, D.,, H. Kallstrom,, S. Normark,, and A. B. Jonsson. 1998. Transcellular passage of Neisseria gonorrhoeae involves pilus phase variation. Infect. Immun. 66:469473.
113. Jarvis, G. A. 1995. Recognition and control of neisserial infection by antibody and complement. Trends Microbiol. 3:198201.
114. Jensen, E. T.,, A. Kharazmi,, K. Lam,, J. W. Costerton,, and N. Hoiby. 1990. Human polymorphonuclear leukocyte response to Pseudomonas aeruginosa grown in biofilms. Infect. Immun. 58: 23832385.
115. Jerse, A. E.,, M. S. Cohen,, P. M. Drown,, L. G. Whicker,, S. F. Isbey,, H. S. Seifert,, and J. G. Cannon. 1994. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J. Exp. Med. 179:911920.
116. Jindani, A.,, V. R. Aber,, E. A. Edwards,, and D. A. Mitchison. 1980. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am. Rev. Respir. Dis. 121:939949.
117. Johnson, W. D., Jr, E. W. Hook, E. Lindsey, and D. Kaye. 1973. Treatment of chronic typhoid carriers with ampicillin. Antimicrob. Agents. Chemother. 3:439440.
118. Jones, B. D.,, and S. Falkow. 1996. Salmonellosis: host immune responses and bacterial virulence determinants. Annu. Rev. Immunol. 14:533561.
119. Jones, B. D. 1997. Host responses to pathogenic Salmonella infection. Genes Dev. 11:679687.
120. Kallstrom, H.,, M. S. Islam,, P. O. Berggren,, and A. B. Jonsson. 1998. Cell signaling by the type IV pili of pathogenic Neisseria. J. Biol. Chem. 273:2177721782.
121. Kallstrom, H.,, M. K. Liszewski,, J. P. Atkinson,, and A. B. Jonsson. 1997. Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol. Microbiol. 25:639 647.
122. Kaye, D.,, J. G. Merselis, Jr., S. Connolly, and E. W. Hook. 1967. Treatment of chronic enteric carriers of Salmonella typhosa with ampicillin. Ann. N. Y. Acad. Sci. 145:429435.
123. Keeling, M. J. 1997. Modelling the persistence of measles. Trends Microbiol. 5:513518.
124. Keeling, M. J.,, and B. T. Grenfell. 1997. Disease extinction and community size: modelling the persistence of measles. Science 275:6567.
125. Kellogg, D. S.,, W. L. Peacock,, W. E. Deacon,, L. Brown,, and C. I. Pirkle. 1963. Neisseria gonorrhoeae. I. Virulence genetically linked to clonal variation. J. Bacteriol. 85:12741279.
126. Kerle, K. K.,, J. R. Mascola,, and T. A. Miller. 1992. Disseminated gonococcal infection. Am. Fam. Physician 45:209214.
127. Kilian, M.,, J. Mestecky,, and M. W. Russell. 1988. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol. Rev. 52:296303.
128. Kilian, M.,, J. Reinholdt,, H. Lomholt,, K. Poulsen,, and E. V. Frandsen. 1996. Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS 104:321338.
129. Kitten, T.,, and A. G. Barbour. 1990. Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii. Proc. Natl. Acad. Sci. USA 87:60776081.
130. Kitten, T.,, and A. G. Barbour. 1992. The relapsing fever agent Borrelia hermsii has multiple copies of its chromosome and linear plasmids. Genetics 132:311324.
131. Kornfeld, H.,, G. Mancino,, and V. Colizzi. 1999. The role of macrophage cell death in tuberculosis. Cell Death Differ. 6:7178.
132. Kuiper, H.,, A. P. van Dam,, L. Spanjaard,, B. M. de Jongh,, A. Widjojokusumo,, T. C. Ramselaar,, I. Cairo,, K. Vos,, and J. Dankert. 1994. Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. Clin. Microbiol. 32:715720.
133. Kupsch, E. M.,, B. Knepper,, T. Kuroki,, I. Heuer,, and T. F. Meyer. 1993. Variable opacity (Opa) outer membrane proteins account for the cell tropisms displayed by Neisseria gonorrhoeae for human leukocytes and epithelial cells. EMBO J. 12:641650.
134. Lawrence, J. R.,, D. R. Korber,, B. D. Hoyle,, J. W. Costerton,, and D. E. Caldwell. 1991. Optical sectioning of microbial biofilms. J. Bacteriol. 173:65586567.
135. Lewinski, M. A.,, J. N. Miller,, M. A. Lovett,, and D. R. Blanco. 1999. Correlation of immunity in experimental syphilis with serum-mediated aggregation of Treponema pallidum rare outer membrane proteins. Infect. Immun. 67:36313636.
136. Li, Z.,, C. Kelley,, F. Collins,, D. Rouse,, and S. Morris. 1998. Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs. J. Infect. Dis. 177:10301035.
137. Lin, L.,, P. Ayala,, J. Larson,, M. Mulks,, M. Fukuda,, S. Carlsson,, C. Enns,, and M. So. 1997. The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells. Mol. Microbiol. 24:10831094.
138. Livey, I.,, C. P. Gibbs,, R. Schuster,, and F. Dorner. 1995. Evidence for lateral transfer and recombination in OspC variation in Lyme disease Borrelia. Mol. Microbiol. 18:257269.
139. Lukehart, S. A. 1982. Activation of macrophages by products of lymphocytes from normal and syphilitic rabbits. Infect. Immun. 37:6469.
140. Lukehart, S. A.,, S. A. Baker-Zander,, R. M. Lloyd,, and S. Sell. 1980a. Characterization of lymphocyte responsiveness in early experimental syphilis. II. Nature of cellular infiltration and Treponema pallidum distribution in testicular lesions. J. Immunol. 124:461467.
141. Lukehart, S. A.,, S. A. Baker-Zander,, and S. Sell. 1980b. Characterization of lymphocyte responsiveness in early experimental syphilis. I. In vitro response to mitogens and Treponema pallidum antigens. J. Immunol. 124:454460.
142. Lukehart, S. A.,, and J. N. Miller. 1978. Demonstration of the in vitro phagocytosis of Treponema pallidum by rabbit peritoneal macrophages. J. Immunol. 121:2014-–2024.
143. Lukehart, S. A.,, J. M. Shaffer,, and S. A. Baker-Zander. 1992. A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence. J. Infect. Dis. 166: 14491453.
144. Mahenthiralingam, E.,, M. E. Campbell,, and D. P. Speert. 1994. Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect. Immun. 62:596605.
145. Mahenthiralingam, E.,, and D. P. Speert. 1995. Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum. Infect. Immun. 63:45194523.
146. Malik, Z. A.,, G. M. Denning,, and D. J. Kusner. 2000. Inhibition of Ca2+ signaling by Mycobacterium tuberculosis is associated with reduced phagosome-lysosome fusion and increased survival within human macrophages. J. Exp. Med. 191:287302.
147. Mandrell, R. E.,, and M. A. Apicella. 1993. Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS. Immunobiology 187:382402.
148. Marconi, R. T.,, M. E. Konkel,, and C. F. Garon. 1993. Variability of osp genes and gene products among species of Lyme disease spirochetes. Infect. Immun. 61:26112617.
149. Marsh, P. D. 1994. Microbial ecology of dental plaque and its significance in health and disease. Adv. Dent. Res. 8:263271.
150. Maskell, D. J.,, and C. E. Hormaeche. 1985. Relapse following cessation of antibiotic therapy for mouse typhoid in resistant and susceptible mice infected with salmonellae of differing virulence. J. Infect. Dis. 152:10441049.
151. McCormack, W.,, R. Stumacher,, K. Johnson,, and A. Donner. 1977. Clinical spectrum of gonococcal infection in women. Lancet i:11821185.
152. McCune, R. M.,, F. M. Feldmann,, H. P. Lambert,, and W. Mc- Dermott. 1966a. Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J. Exp. Med. 123:445468.
153. McCune, R. M.,, F. M. Feldmann,, and W. McDermott. 1966b. Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli. J. Exp. Med. 123:469486.
154. McCune, R.,, S. H. Lee,, K. Deuschle,, and W. McDermott. 1957. Ineffectiveness of isoniazid in modifying the phenomenon of microbial persistence. Am. Rev. Tuberc. Pulm. Dis. 76:11061109.
155. McCune, R. M.,, and R. Tompsett. 1956. Fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. I. The persistence of drug-susceptible tubercle bacilli in the tissues despite prolonged antimicrobial therapy. J. Exp. Med. 104:737762.
156. McCune, R. M.,, R. Tompsett,, and W. McDermott. 1956. Fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug. J. Exp. Med. 104:763801.
157. McGrath, J. W. 1988. Social networks of disease spread in the Lower Illinois Valley: a simulation approach. Am. J. Phys. Anthropol. 77:483496.
158. McKinney, J. D.,, B. R. Bloom,, and R. L. Modlin,. 2001. Tuberculosis and leprosy, p. 9951012. In K. F. Austen,, M. M. Frank,, J. P. Atkinson,, and H. Cantor (ed.), Samter’s Immunologic Diseases, 6th ed., in press. Lippincott Williams & Wilkins, Baltimore, Md..
159. McKinney, J. D.,, K. Höner zu Bentrup,, E. J. Muñoz-Elías,, A. Miczak,, B. Chen,, W. T. Chan,, D. Swenson,, J. C. Sacchettini,, W. R. Jacobs, Jr., and D. G. Russell. 2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:735738.
160. McKinney, J. D.,, W. R. Jacobs,, and B. R. Bloom,. 1998. Persisting problems in tuberculosis, p. 51146. In R. Krause,, J. I. Gallin,, and A. S. Fauci (ed.), Emerging Infections. Academic Press, New York, N.Y..
161. McLean, R. J.,, M. Whiteley,, D. J. Stickler,, and W. C. Fuqua. 1997. Evidence of autoinducer activity in naturally occurring biofilms. FEMS Microbiol. Lett. 154:259263.
162. Meier, J. T.,, M. I. Simon,, and A. G. Barbour. 1985. Antigenic variation is associated with DNA rearrangements in a relapsing fever Borrelia. Cell 41:403409.
163. Meleney, H. E. 1928. Relapse phenomena of Spironema recurrentis. J. Exp. Med. 48:6582.
164. Meyer, T. F.,, C. P. Gibbs,, and R. Haas. 1990. Variation and control of protein expression in Neisseria. Annu. Rev. Microbiol. 44:451477.
165. Minor, S. Y.,, and E. C. Gotschlich,. 2000. The genetics of LPS synthesis by the gonococcus, p. 111131. In J. B. Goldberg (ed.), Genetics of Bacterial Polysaccharides. CRC Press, Inc., Boca Raton, Fla..
166. Mitchison, D. A. 1979. Basic mechanisms of chemotherapy. Chest 76(Suppl.):771781.
167. Mitchison, D. A. 1980. Treatment of tuberculosis. J. R. Coll. Physicians London 14:9199.
168. Moran, A. P.,, M. M. Prendergast,, and B. J. Appelmelk. 1996. Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol. Med. Microbiol. 16:105115.
169. Moxon, E. R.,, P. B. Rainey,, M. A. Nowak,, and R. E. Lenski. 1994. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4:2433.
170. Murray, P. J. 1999. Defining the requirements for immunological control of mycobacterial infections. Trends Microbiol. 7:366371.
171. Nassif, X.,, and M. So. 1995. Interaction of pathogenic neisseriae with nonphagocytic cells. Clin. Microbiol. Rev. 8:376388.
172. Nassif, X.,, C. Pujol,, P. Morand,, and E. Eugene. 1999. Interactions of pathogenic Neisseria with host cells—is it possible to assemble the puzzle? Mol. Microbiol. 32:11241132.
173. Naumann, M.,, S. Wessler,, C. Bartsch,, B. Wieland,, and T. F. Meyer. 1997. Neisseria gonorrhoeae epithelial cell interaction leads to the activation of the transcription factors nuclear factor kappaB and activator protein 1 and the induction of inflammatory cytokines. J. Exp. Med. 186:247258.
174. Norris, S. J.,, J. K. Howell,, S. A. Garza,, M. S. Ferdows,, and A. G. Barbour. 1995. High- and low-infectivity phenotypes of clonal populations of in vitro-cultured Borrelia burgdorferi. Infect. Immun. 63:22062212.
175. Nyka, W. 1962. Studies on the infective particle in air-borne tuberculosis. I. Observations in mice infected with a bovine strain of M. tuberculosis. Am. Rev. Respir. Dis. 85:3339.
176. Ochman, H.,, J. G. Lawrence,, and E. A. Groisman. 2000. Lateral gene transfer and the nature of bacterial innovation. Nature 405:299304.
177. Ochman, H.,, F. C. Soncini,, F. Solomon,, and E. A. Groisman. 1996. Identification of a pathogenicity island required for Salmonella survival in host cells. Proc. Natl. Acad. Sci. USA 93: 78007804.
178. Oksi, J.,, J. Savolainen,, J. Pène,, J. Bousquet,, P. Laippala,, and M. K. Viljanen. 1996. Decreased interleukin-4 and increased gamma interferon production by peripheral blood mononuclear cells of patients with Lyme borreliosis. Infect. Immun. 64:36203623.
179. Oliver, A.,, R. Canton,, P. Campo,, F. Baquero,, and J. Blazquez. 2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:12511254.
180. Oriel, J. D. 1991. Noeggerath and ‘‘latent’’ gonorrhea. Sex. Transm. Dis. 18:8991.
181. Orme, I. M.,, and A. M. Cooper. 1999. Cytokine /chemokine cascades in immunity to tuberculosis. Immunol. Today 20:307312.
182. O’Toole, G. A.,, K. A. Gibbs,, P. W. Hager,, P. V. Phibbs, Jr., and R. Kolter. 2000. The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa. J. Bacteriol. 182:425431.
183. O’Toole, G. A.,, and R. Kolter. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30:295304.
184. Ottenhoff, T. H. M.,, D. Kumararatne,, and J. L. Casanova. 1998. Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria. Immunol. Today 19:491494.
185. Ovcinnikov, N. M.,, and V. V. Delektorskij. 1972. Electron microscopy of phagocytosis in syphilis and yaws. Br. J. Vener. Dis. 48:227248.
186. Paavonen, J. 1998. Pelvic inflammatory disease—from diagnosis to prevention. Dermatol. Clin. 16:747756.
187. Pachner, A. R.,, E. Delaney,, and T. O’Neill. 1995. Neuroborreliosis in the nonhuman primate: Borrelia burgdorferi persists in the central nervous system. Ann. Neurol. 38:667669.
188. Pang, T.,, M. M. Levine,, B. Ivanoff,, J. Wain,, and B. B. Finlay. 1998. Typhoid fever—important issues still remain. Trends Microbiol. 6:131133.
189. Panum, P. L. 1847. Iagttagelser, anstillede under Maeslinge- Epidemien paa Faeroerne i Aaret 1846. Virch. Arch. 1:492504. (Translated by Hatcher, A.S., 1939, Observations made during the epidemic of measles on the Faroe Islands in the year 1846, Med. Classics 3:829840.).
190. Parrish, N. M.,, J. D. Dick,, and W. R. Bishai. 1998. Mechanisms of latency in Mycobacterium tuberculosis. Trends Microbiol. 6: 107112.
191. Parsons, N. J.,, J. R. Andrade,, P. V. Patel,, J. A. Cole,, and H. Smith. 1989. Sialylation of lipopolysaccharide and loss of absorption of bactericidal antibody during conversion of gonococci to serum resistance by cytidine 5′-monophospho-N-acetyl neuraminic acid. Microb. Pathog. 7:6372.
192. Pennington, P. M.,, D. Cadavid,, and A. G. Barbour. 1999. Characterization of VspB of Borrelia turicatae, a major outer membrane protein expressed in blood and tissues of mice. Infect. Immun. 67:46374645.
193. Persing, D. H.,, D. Mathiesen,, D. Podzorski,, and S. W. Barthold. 1994. Genetic stability of Borrelia burgdorferi recovered from chronically infected immunocompetent mice. Infect. Immun. 62:35213527.
194. Philipp, M. T. 1998. Studies on OspA: a source of new paradigms in Lyme disease research. Trends Microbiol. 6:4447.
195. Plasterk, R. H.,, M. I. Simon,, and A. G. Barbour. 1985. Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii. Nature 318:257263.
196. Pratt, L. A.,, and R. Kolter. 1998. Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol. Microbiol. 30:285293.
197. Pratt, L. A.,, and R. Kolter. 1999. Genetic analyses of bacterial biofilm formation. Curr. Opin. Microbiol. 2:598603.
198. Quétel, C. 1990. History of Syphilis. Johns Hopkins University Press, Baltimore, Md. .
199. Radolf, J. D. 1994. Role of outer membrane architecture in immune evasion by Treponema pallidum and Borrelia burgdorferi. Trends Microbiol. 2:307311.
200. Radolf, J. D. 1995. Treponema pallidum and the quest for outer membrane proteins. Mol. Microbiol. 16:10671073.
201. Radolf, J. D.,, M. V. Norgard,, and W. W. Schulz. 1989. Outer membrane ultrastructure explains the limited antigenicity of virulent Treponema pallidum. Proc. Natl. Acad. Sci. USA 86:20512055.
202. Radolf, J. D.,, B. Steiner,, and D. Shevchenko. 1999. Treponema pallidum: doing a remarkable job with what it’s got. Trends Microbiol. 7:79.
203. Ram, S.,, F. G. Mackinnon,, S. Gulati,, D. P. McQuillen,, U. Vogel,, M. Frosch,, C. Elkins,, H. K. Guttormsen,, L. M. Wetzler,, M. Oppermann,, M. K. Pangburn,, and P. A. Rice. 1999. The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis. Mol. Immunol. 36: 915928.
204. Rathman, M.,, L. P. Barker,, and S. Falkow. 1997. The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infect. Immun. 65:14751485.
205. Rathman, M.,, M. D. Sjaastad,, and S. Falkow. 1996. Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infect. Immun. 64:27652773.
206. Restrepo, B. I.,, and A. G. Barbour. 1994. Antigen diversity in the bacterium B. hermsii through ‘‘somatic’’ mutations in rearranged vmp genes. Cell 78:867876.
207. Restrepo, B. I.,, C. J. Carter,, and A. G. Barbour. 1994. Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever. Mol. Microbiol. 13:287299.
208. Rich, A. R.,, A. M. Chesney,, and T. B. Turner. 1933. Experiments demonstrating that acquired immunity in syphilis is not dependent upon allergic inflammation. Johns Hopkins Hosp. Bull. 52: 179202.
209. Roberts, E. D.,, R. P. Bohm, Jr.,, F. B. Cogswell,, H. N. Lanners,, R. C. Lowrie, Jr.,, L. Povinelli,, J. Piesman,, and M. T. Philipp. 1995. Chronic Lyme disease in the rhesus monkey. Lab. Invest. 72:146160.
210. Rothbard, J. B.,, R. Fernandez,, L. Wang,, N. N. Teng,, and G. K. Schoolnik. 1985. Antibodies to peptides corresponding to a conserved sequence of gonococcal pilins block bacterial adhesion. Proc. Natl. Acad. Sci. USA 82:915919.
211. Rowe, B.,, L. R. Ward,, and E. J. Threlfall. 1997. Multidrug-resistant Salmonella typhi: a worldwide epidemic. Clin. Infect. Dis. 24(Suppl. 1):S106S109.
212. Rudenko, G.,, M. Cross,, and P. Borst. 1998. Changing the end: antigenic variation orchestrated at the telomeres of African trypanosomes. Trends Microbiol. 6:113116.
213. Russell, D. G., 2000. What is the very model of a modern macrophage pathogen?, p. 107117. In K. A. Brogden,, J. A. Roth,, T. B. Stanton,, C. A. Bolin,, F. C. Minion,, and M. J. Wannemuehler (ed.) Virulence Mechanisms of Bacterial Pathogens. ASM Press, Washington, D.C..
214. Saint Girons, I.,, and A. G. Barbour. 1991. Antigenic variation in Borrelia. Res. Microbiol. 142:711717.
215. Samandari, T.,, M. M. Levine,, and M. B. Sztein,. 2000. Mechanisms for establishing persistence: immune modulation, p. 5378. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
216. Sauer, G. C.,, and J. C. Hall,. 1996. Spirochetal infections, p. 174186. In G. C. Sauer, and J. C. Hall (ed.), Manual of Skin Diseases, 7th ed., Lippincott-Raven, Philadelphia, Pa..
217. Schaible, U. E.,, S. Sturgill-Koszycki,, P. H. Schlesinger,, and D. G. Russell. 1998. Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages. J. Immunol. 160:12901296.
218. Schneider, H.,, J. M. Griffiss,, J. W. Boslego,, P. J. Hitchcock,, K. M. Zahos,, and M. A. Apicella. 1991. Expression of paragloboside-like lipooligosaccharides may be a necessary component of gonococcal pathogenesis in men. J. Exp. Med. 174:16011605.
219. Schuhardt, V. T.,, and M. Wilkerson. 1951. Relapse phenomena in rats infected with single spirochetes (Borrelia recurrentis var. turicatae). J. Bacteriol. 62:215219.
220. Schwan, T. G.,, and B. J. Hinnebusch. 1998. Bloodstream-versus tick-associated variants of a relapsing fever bacterium. Science 280:19381940.
221. Segal, E.,, E. Billyard,, M. So,, S. Storzbach,, and T. F. Meyer. 1985. Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation. Cell 40:293300.
222. Seifert, H. S. 1996. Questions about gonococcal pilus phase- and antigenic variation. Mol. Microbiol. 21:433440.
223. Seifert, H. S.,, C. J. Wright,, A. E. Jerse,, M. S. Cohen,, and J. G. Cannon. 1994. Multiple gonococcal pilin antigenic variants are produced during experimental human infections. J. Clin. Invest. 93:27442749.
224. Sell, S.,, D. Gamboa,, S. A. Baker-Zander,, S. A. Lukehart,, and J. N. Miller. 1980. Host response to Treponema pallidum in intradermally- infected rabbits: evidence for persistence of infection at local and distant sites. J. Investig. Dermatol. 75:470475.
225. Shafer, W. M.,, and R. F. Rest. 1989. Interactions of gonococci with phagocytic cells. Annu. Rev. Microbiol. 43:121145.
226. Shiloh, M.,, and C. F. Nathan. 2000. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA 97:88418848.
227. Shukla, V. K.,, H. Singh,, M. Pandey,, S. K. Upadhyay,, and G. Nath. 2000. Carcinoma of the gallbladder—is it a sequel of typhoid? Dig. Dis. Sci. 45:900903.
228. Sigal, L. H. 1997. Lyme disease: a review of aspects of its immunology and immunopathogenesis. Annu. Rev. Immunol. 15: 6392.
229. Sinai, A. P., 2000. Life on the inside: microbial strategies for intracellular survival and persistence, p. 3151. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
230. Singh, A. E.,, and B. Romanowski. 1999. Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. Clin. Microbiol. Rev. 12:187209.
231. Slauch, J.,, R. Taylor,, and S. Maloy. 1997. Survival in a cruel world: how Vibrio cholerae and Salmonella respond to an unwilling host. Genes Dev. 11:17611774.
232. Small, P. M.,, and U. M. Selcer,. 1999. Human immunodeficiency virus and tuberculosis, p. 329338. In D. Schlossberg (ed.), Tuberculosis and Nontuberculous Mycobacterial Infections. The W. B. Saunders Co., Philadelphia, Pa..
233. Smith, H.,, N. Parsons,, and J. Cole. 1995. Sialylation of neisserial lipopolysaccharide: a major influence on pathogenicity. Microb. Pathog. 19:365377.
234. Smith, K. J.,, H. G. Skelton,, and E. Abell,. 2000. Spirochetal infections, p. 579601. In E. R. Farmer,, and A. F. Hood (ed.), Pathology of the Skin, 2nd ed. McGraw-Hill Book Co., New York, N.Y..
235. Steere, A. C.,> 1989. Lyme disease. N. Engl. J. Med. 321:586596. Stenger, S.,, and R. L. Modlin. 1999. T cell mediated immunity to Mycobacterium tuberculosis. Curr. Opin. Microbiol. 2:8993.
236. Stenger, S.,, J. P. Rosat,, B. R. Bloom,, A. M. Krensky,, and R. L. Modlin. 1999. Granulysin: a lethal weapon of cytotoxic T cells. Immunol. Today 20:390394.
237. Stern, A.,, M. Brown,, P. Nickel,, and T. F. Meyer. 1986. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47:6171.
238. Stern, A.,, P. Nickel,, T. F. Meyer,, and M. So. 1984>. Opacity determinants of Neisseria gonorrhoeae: gene expression and chromosomal linkage to the gonococcal pilus gene. Cell 37:447 456.
239. Stevenson, B.,, L. K. Bockenstedt,, and S. W. Barthold. 1994. Expression and gene sequence of outer surface protein C of Borrelia burgdorferi reisolated from chronically infected mice. Infect. Immun. 62:35683571.
240. Stickler, D. J.,, N. S. Morris,, R. J. McLean,, and C. Fuqua. 1998. Biofilms on indwelling urethral catheters produce quorum- sensing signal molecules in situ and in vitro. Appl. Environ. Microbiol. 64:34863490.
241. Stoenner, H. G.,, T. Dodd,, and C. Larsen. 1982. Antigenic variation of Borrelia hermsii. J. Exp. Med. 156:12971311.
242. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddiz,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser,, and D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton- ATPase. Science 263:678681.
243. Suk, K.,, S. Das,, W. Sun,, B. Jwang,, S. W. Barthold,, R. A. Flavell,, and E. Fikrig. 1995. Borrelia burgdorferi genes selectively expressed in the infected host. Proc. Natl. Acad. Sci. USA 92:4269 4273.
244. Sukupolvi, S.,, A. Edelstein,, M. Rhen,, S. J. Normark,, and J. D. Pfeifer. 1997. Development of a murine model of chronic Salmonella infection. Infect. Immun. 65:838842.
245. Swanson, J. 1973. Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. J. Exp. Med. 137:571589.
246. Swanson, J.,, O. Barrera,, J. Sola,, and J. Boslego. 1988. Expression of outer membrane protein II by gonococci in experimental gonorrhea. J. Exp. Med. 168:21212129.
247. Taylor, D. N.,, and M. J. Blaser. 1991. The epidemiology of Helicobacter pylori infection. Epidemiol. Rev. 13:4259.
248. Ting, L.-M.,, A. C. Kim,, A. Cattamanchi,, and J. D. Ernst. 1999. Mycobacterium tuberculosis inhibits IFN-γ transcriptional responses without inhibiting activation of STAT1. J. Immunol. 163:38983906.
249. Trucksis, M., 2000. Mycobacterium infections. In J. P. Nataro,, M. J. Blaser,, and S. Cunningham-Rundles (ed.), Persistent Bacterial Infections. ASM Press, Washington, D.C..
250. Uchiya, K.,, M. A. Barbieri,, K. Funato,, A. H. Shah,, P. D. Stahl,, and E. A. Groisman. 1999. A Salmonella virulence protein that inhibits cellular trafficking. EMBO J. 18:39243933.
251. Valdivia, R. H.,, and S. Falkow. 1997. Fluorescence-based isolation of bacterial genes expressed within host cells. Science 277:20072011.
252. Valway, S. E.,, M. P. C. Sanchez,, T. F. Shinnick,, I. Orme,, T. Agerton,, D. Hoy,, J. S. Jones,, H. Westmoreland,, and I. M. Onorato. 1998. An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis. N. Engl. J. Med. 338:633639.
253. Vandiviere, H. M.,, W. E. Loring,, I. Melvin,, and S. Willis. 1956. The treated pulmonary lesion and its tubercle bacillus. II. The death and resurrection. Am. J. Med. Sci. 232:3037.
254. Vanham, G.,, Z. Toossi,, C. S. Hirsch,, R. S. Wallis,, S. K. Schwander,, E. A. Rich,, and J. J. Ellner. 1997. Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression / anergy. Tuberc. Lung Dis. 78:145158.
255. van Heyningen, T. K.,, H. L. Collins,, and D. G. Russell. 1997. IL- 6 produced by macrophages infected with Mycobacterium species suppresses T cell responses. J. Immunol. 158:330337.
256. van Putten, J. P. 1993. Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae. EMBO J. 12:40434051.
257. van Putten, J. P.,, and B. D. Robertson. 1995. Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria. Mol. Microbiol. 16:847853.
258. van Voorhis, W. C.,, L. K. Barrett,, D. M. Koelle,, J. M. Nasio,, F. A. Plummer,, and S. A. Lukehart. 1996a. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J. Infect. Dis. 173:491495.
259. van Voorhis, W. C.,, L. K. Barrett,, J. M. Nasio,, F. A. Plummer,, and S. A. Lukehart. 1996b. Lesions of primary and secondary syphilis contain activated cytolytic T cells. Infect. Immun. 64: 10481050.
260. Vazquez-Torres, A.,, and F. C. Fang,. 2000. Mechanisms of resistance to NO-related antibacterial activity, p. 131142. In K. A. Brogden,, J. A. Roth,, T. B. Stanton,, C. A. Bolin,, F. C. Minion,, and M. J. Wannemuehler (ed.), Virulence Mechanisms of Bacterial Pathogens. ASM Press, Washington, D.C..
261. Vazquez-Torres, A.,, J. Jones-Carson,, A. J. Baumler,, S. Falkow,, R. Valdivia,, W. Brown,, M. Le,, R. Berggren,, W. T. Parks,, and F. C. Fang. 1999. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401:804808.
262. Vazquez-Torres, A.,, Y. Xu,, J. Jones-Carson,, D. W. Holden,, S. M. Lucia,, M. C. Dinauer,, P. Mastroeni,, and F. C. Fang. 2000. Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase. Science 287:16551658.
263. Via, L. E.,, R. A. Fratti,, M. McFalone,, E. Pagan-Ramos,, D. Deretic,, and V. Deretic. 1998. Effects of cytokines on mycobacterial phagosome maturation. J. Cell. Sci. 111:897905.