Chapter 12 : Chlamydial Persistence Redux

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

Preview this chapter:
Zoom in

Chlamydial Persistence Redux, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817329/9781555816742_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555817329/9781555816742_Chap12-2.gif


The purpose of this chapter is to define what one do and do not know about chlamydial persistence with the goal of determining the extent of the role that persistence plays in chlamydial disease (if at all) and what one should do to better understand this chlamydial attribute. Out of , , , and ) causing infections in people, only two dominates: and . , which causes a form of malaria called malignant tertian malaria, is considered a major killer due to its capacity to modify the surface of infected erythrocytes such that they stick to each other and to the endothelial cells lining vessels and capillaries. may be one of only a very few bacterial pathogens that is more difficult to work with than . Environmental factors that trigger dormancy include starvation for nutrients and hypoxia. When these stress-related conditions are applied to , striking metabolic reprogramming occurs, including upregulation of stress response genes and downregulation of many central metabolism genes. Studies of persistent disease in mice indicate that persistence is a function of the capacity of the pathogen to survive in macrophages, and at least for nontyphoidal salmonellae, macrophage persistence contributes to increased disease severity in AIDS patients. The authors conclude that persistent forms may account for the insidious inflammation associated with upper genital tract disease in women, but have not been able to identify that persistent infections act as contributing factors to the disease.

Citation: Byrne G, Beatty W. 2012. Chlamydial Persistence Redux, p 265-284. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch12
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Schematic diagram of the chlamydial developmental cycle. Red arrows indicate altered intracellular chlamydial development mediated by environmental factors. (A) Immunofluorescence images and schematic show mature serovar B inclusions with elementary bodies (EBs) in green (anti-OmcB), reticulate bodies (RBs) in red (anti-major outer membrane protein), and the inclusion membrane in orange (anti-incG). (B) Persistence in vitro in response to IFN-γ results in enlarged, aberrant RBs that can be maintained in this state for extended periods of time, with subsequent reversion to normal intracellular development. doi:10.1128/9781555817329.ch12.f1

Citation: Byrne G, Beatty W. 2012. Chlamydial Persistence Redux, p 265-284. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Chlamydial inclusions in intestinal enterocytes of naturally infected swine. (A) Lower-magnification electron micrograph showing both a typical inclusion (indicated by arrow) with an abundance of dense EBs and inclusions containing somewhat enlarged RBs (arrowheads). (B) Higher-magnification electron micrograph showing an inclusion containing typical EBs and RBs, in addition to enlarged, aberrant RBs (arrowheads). It is interesting that both normal and abnormal developmental forms are seen, as if persistence is a stochastic event for infecting the pig intestine. Images generously provided by Andreas Pospischil, University of Zurich. doi: 10.1128/9781555817329.ch12.f2

Citation: Byrne G, Beatty W. 2012. Chlamydial Persistence Redux, p 265-284. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Factors contributing to persistence of other microorganisms and potential correlates in . Attributes of other microorganisms are shown in upper panels, and potential correlates in are shown in the corresponding lower panels. Please see the text for details. doi:10.1128/9781555817329.ch12.f3

Citation: Byrne G, Beatty W. 2012. Chlamydial Persistence Redux, p 265-284. In Tan M, Bavoil P (ed), Intracellular Pathogens I: . ASM Press, Washington, DC. doi: 10.1128/9781555817329.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint


1. AbdelRahman, Y. M.,, L. A. Rose,, and R. J. Belland. 2011. Developmental expression on non-coding RNAs in Chlamydia trachomatis during normal and persistent growth. Nucleic Acids Res. 39: 1843 1854. PubMed CrossRef
2. Akers, J. C.,, and M. Tan. 2006. Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis. J. Bacteriol. 188: 4236 4243. PubMed CrossRef
3. Baughn, R. E.,, and D. M. Musher. 2005. Secondary syphylitic lesions. Clin. Microbiol. Rev. 18: 205 216. PubMed CrossRef
4. Beatty, W. L.,, R. P. Morrison,, and G. I. Byrne. 1994. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol. Rev. 58: 686 699. PubMed
5. Byrne, G. I.,, L. K. Lehmann,, and G. L. Landry. 1986. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect. Immun. 53: 347 351. PubMed
6. Byrne, G. I.,, and D. Ojcius. 2004. Chlamydia and apoptosis: life and death decisions of an intracellular pathogen. Nat. Rev. Microbiol. 2: 802 808. PubMed CrossRef
7. Caldwell, H. D.,, H. Wood,, D. Crane,, R. Bailey,, R. B. Jones,, D. Mabey,, I. MacLean,, Z. Mohammed,, R. Peeling,, C. Roshick,, J. Schachter,, A. W. Solomon,, W. E. Stamm,, R. L. Suchland,, L. Taylor,, S. K. West,, T. C. Quinn,, R. J. Belland,, and G. McClarty. 2003. Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates. J. Clin. Investig. 111: 1757 1769. PubMed CrossRef
8. Carlson, J. H.,, H. Wood,, C. Roshick,, H. D. Caldwell,, and G. McClarty. 2006. In vivo and in vitro studies of C. trachomatis TrpR:DNA interactions. Mol. Microbiol. 59: 1678 1691. PubMed CrossRef
9. Carter, J. D.,, and A. P. Hudson. 2010. The evolving story of Chlamydia-induced reactive arthritis. Curr. Opin. Rheumatol. 22: 424 430. PubMed CrossRef
10. Chao, M. C.,, and E. J. Rubin. 2010. Letting sleeping dos lie: does dormancy play a role in tuberculosis? Annu. Rev. Microbiol. 64: 293 311. PubMed CrossRef
11. Chen, N.,, A. Auliff,, K. Riekmann,, M. Gatton,, and Q. Cheng. 2007. Relapses of Plasmodium vivax result from clonal hypnozoites activated at predetermined intervals. J. Infect. Dis. 195: 934 941. PubMed CrossRef
12. Geisler, W. M. 2010. Duration of untreated, uncomplicated Chlamydia trachomatis genital infection and factors associated with chlamydia resolution: a review of human studies. J. Infect. Dis. 201( S2): S104 S113. PubMed CrossRef
13. Gerard, H.,, J. Whittum-Hudson,, H. R. Schumacher,, and A. Hudson. 2004. Differential expression of three C. trachomatis hsp-60-encoding genes in active vs persistent infections. Microb. Pathog. 36: 35 39. PubMed
14. Goellner, S.,, E. Schubert,, E. Lieber-Tenorio,, H. Hotzel,, H. P. Saluz,, and K. Sache. 2006. Transcriptional response patterns of Chlamydophila psittaci in different in vitro models of persistent infection. Infect. Immun. 74: 4801 4808. PubMed CrossRef
15. Gordon, M. A. 2008. Salmonella infections in immunocompromised adults. J. Infect. 56: 413 422. PubMed CrossRef
16. Hensel, M. 2000. Salmonella pathogenicity island 2. Mol. Microbiol. 36: 1015 1023.
17. Hogan, R. J.,, S. A. Mathews,, S. Mukhopadhyay,, J. T. Summersgill,, and P. Timms. 2004. Chlamydial persistence: beyond the basic paradigm. Infect. Immun. 72: 1843 1855. PubMed
18. Horn, M.,, A. Collingro,, S. Schmitz-Esser,, C. L. Beier,, U. Purkhold,, B. Fartmann,, P. Brandt,, G. J. Nyakatura,, M. Droege,, D. Frishman,, T. Rattei,, H.-W. Mewes,, and M. Wagner. 2004. Illuminating the evolutionary history of Chlamydia. Science 304: 728 730. PubMed CrossRef
19. Howe, D. K.,, and D. L. Sibley. 1995. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J. Infect. Dis. 172: 1561 1566. PubMed CrossRef
20. Hower, S.,, K. Wolf,, and K. Fields. 2009. Evidence that CT694 is a novel Chlamydia trachomatis T3S substrate capable of functioning during invasion or early cycle development. Mol. Microbiol. 72: 1423 1437. PubMed CrossRef
21. Hunter, J. 1818. Treatise on Venereal Disease, 2nd ed. Sherwood, Neely, and Jones, London, United Kingdom.
22. Ieven, M. M.,, and V. Y. Hoymans. 2005. Involvement of Chlamydia pneumoniae in atherosclerosis: more evidence for lack of evidence. J. Clin. Microbiol. 43: 19 24. PubMed CrossRef
23. Imwong, M.,, G. Snounou,, S. Pukrittayakamee,, N. Tanomsing,, J. R. Kim,, A. Nandy,, J. P. Guthmann,, F. Nosten,, J. Carlton,, S. Looareesuwan,, S. Nair,, D. Sudimack,, N. P. J. Day,, T. J. C. Anderson,, and N. J. White. 2007. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J. Infect. Dis. 195: 927 933. PubMed CrossRef
24. Kimani, J.,, I. W. Maclean,, J. J. Bwayo,, K. MacDonald,, J. Oyugi,, G. M. Maitha,, R. W. Peeling,, M. Cheang,, N. J. D. Nagelkerke,, F. A. Plummer,, and R. C. Brunham. 1996. Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya. J. Infect. Dis. 173: 1437 1444. PubMed CrossRef
25. Kumar, A.,, J. C. Toleda,, R. P. Patel,, J. R. Lancaster, Jr.,, and A. J. Steyn. 2007. Mycobacterium tuberculosis DosS is a redo sensor and DosT is a hypoxia sensor. Proc. Natl. Acad. Sci. USA 104: 11568 11574. PubMed CrossRef
26. LaFond, R. E.,, and S. A. Lukehart. 2006. Biological basis for syphilis. Clin. Microbiol. Rev. 19: 29 49. PubMed CrossRef
27. Lavollay, M.,, M. Arthur,, M. Fourgeaud,, L. Dubost,, A. M. N. Veziris,, D. Blanot,, L. Gutmann,, and J.-L. Mainardi. 2008. The peptidoglycan of stationary phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation. J. Bacteriol. 190: 4360 4366. PubMed CrossRef
28. Lee, C. K.,, and J. W. Moulder. 1981. Persistent infection of mouse fibroblasts (McCoy cells) with a trachoma strain of Chlamydia trachomatis. Infect. Immun. 32: 822 829. PubMed
29. Lenart, J.,, A. A. Anderson,, and D. D. Rockey. 2001. Growth and development of tetracycline-resistant Chlamydia suis. Antimicrob. Agents Chemother. 42: 2198 2203. PubMed CrossRef
30. Lin, P. L.,, and J. L. Flynn. 2010. Understanding latent tuberculosis: a moving target. J. Immunol. 185: 15 22. PubMed CrossRef
31. Mahoney, J. B.,, and B. K. Coombes. 2001. Chlamydia pneumoniae and atherosclerosis: does the evidence support a causal or contributory role? FEMS Microbiol. Lett. 197: 1 9. PubMed
32. Mathews, S.,, C. George,, C. Flegg,, D. Stenzel,, and P. Timms. 2001. Differential expression of ompA, ompB, pyk, nlpD and Cpn0585 genes between normal and interferon-gamma treated cultures of Chlamydia pneumoniae. Microb. Pathog. 30: 337 345. PubMed CrossRef
33. Matsumoto, A.,, and G. P. Manire. 1970. Electron microscopic observations on the effect of penicillin on the morphology of Chlamydia psittaci. J. Bacteriol. 101: 278 285. PubMed
34. Maurer, A. P.,, A. Mehlitz,, H. J. Mollenkopf,, and T. F. Meyer. 2007. Gene expression profiles of Chlamydophila pneumoniae during the developmental cycle and iron-depleted mediated persistence. PLoS Pathog. 3: e83. PubMed CrossRef
35. McCormack, W. M.,, S. Alpert,, D. E. McComb,, R. L. Nichols,, Z. Semine,, and S. H. Zinner. 1979. Fifteen-month follow-up study of women infected with C. trachomatis. N. Engl. J. Med. 300: 123 125. PubMed CrossRef
36. Mitel, S.,, N. J. Miller,, E. R. Fischer,, and T. Hackstadt. 2010. Specific chlamydial inclusion membrane proteins associated with active Src family kinases in microdomains that interact with the host microtubule network. Cell. Microbiol. 12: 1235 1249. PubMed CrossRef
37. Monack, D. M.,, D. M. Bouley,, and S. Falkow. 2004a. Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFN-γ neutralization. J. Exp. Med. 199: 231 241. PubMed CrossRef
38. Monack, D. M.,, A. Mueller,, and S. Falkow. 2004b. Persistent bacterial infections: the interface of the pathogen and the host immune system. Nat. Rev. Microbiol. 2: 747 765. PubMed CrossRef
39. Montoya, J. G.,, and O. Liesenfeld. 2004. Toxoplasmosis. Lancet 363: 1965 1976.
40. Moulder, J. W.,, N. J. Levy,, and L. P. Shulman. 1980. Persistent infection of mouse fibroblasts (L cells) with Chlamydia psittaci: evidence for a cryptic chlamydial form. Infect. Immun. 30: 874 883. PubMed
41. O’Regan, A. W.,, C. Castro,, S. A. Lukehart,, J. M. Kasznica,, P. A. Rice,, and M. F. Joyce-Brady. 2002. Barking up the wrong tree? Use of polymerase chain reaction to diagnose syphylitic aortitis. Thorax 57: 917 918. PubMed CrossRef
42. Oriel, J. D.,, and G. L. Ridgway. 1982a. Genital infection by Chlamydia trachomatis. Curr. Topics Infect. Dis. 2: 41 52.
43. Oriel, J. D.,, and G. L. Ridgway. 1982b. Genital infection by Chlamydia trachomatis. Curr. Top. Infect. Dis. 2: 53 67.
44. Ouellette, S. P.,, T. P. Hatch,, Y. M. AbdelRahman,, L. A. Rose,, R. J. Belland,, and G. I. Byrne. 2006. Global transcriptional up-regulation in the absence of increased translation in Chlamydia during IFN-γ-mediated host cell tryptophan starvation. Mol. Microbiol. 62: 1387 1401.
45. Papp, J. R.,, and P. E. Shewen. 1996. Localization of chronic Chlamydia psittaci infection in the reproductive tract of sheep. J. Infect. Dis. 174: 1296 1302. PubMed CrossRef
46. Papp, J. R.,, and P. E. Shewen. 1997. Chlamydia psittaci infection in sheep: a paradigm for human reproductive tract infection. J. Reprod. Immunol. 34: 185 202. PubMed
47. Peng, K.,, and D. M. Monack. 2010. Indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs. Infect. Immun. 78: 2723 2733. PubMed CrossRef
48. Pfefferkorn, E. R.,, M. Eckel,, and S. Rebhun. 1986. Interferon-gamma suppresses the growth of Toxoplasma gondii in human fibroblasts through starvation for tryptophan. Mol. Biochem. Parasitol. 20: 215 224. PubMed
49. Pospischil, A.,, N. Borel,, E. H. Chowdury,, and F. Guscetti. 2009. Aberrant chlamydial developmental forms in the gastrointestinal tract of pigs spontaneously and experimentally infected with Chlamydia suis. Vet. Microbiol. 135: 147 156. PubMed CrossRef
50. Ramage, H. R.,, L. E. Connolly,, and J. S. Cox. 2009. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 5: e1000767. PubMed CrossRef
51. Regan, M. J.,, B. J. Wood,, Y. H. Hsieh,, M. L. Theodore,, T. C. Quinn,, D. B. Hellman,, R. Green,, C. A. Gaydos,, and J. H. Stone. 2002. Temporal arteritis and Chlamydia pneumoniae. Failure to detect the organism by polymerase chain reaction in ninety cases and ninety controls. Arthritis Rheum. 46: 1056 1060. PubMed
52. Reinhold, P.,, E. Liebler-Tenorio,, S. Sattler,, and K. Sachse. 2011. Recurrence of Chlamydia suis infection in pigs after short-term antimicrobial treatment. Vet. J. 187: 405 407. PubMed CrossRef
53. Reinhold, P.,, K. Sachse,, and B. Kaltenboeck. 2011. Chlamydiaceae in cattle: commensals, trigger organisms, or pathogens? Vet. J. 189: 257 267. doi:10.1016/j.tvjl.2010.09.003. PubMed CrossRef
54. Richmond, S. J.,, A. L. Hilton,, and S. K. R. Clarke. 1972. Chlamydial infection. Role of Chlamydia sub-group A in non-gonococcal and post-gonococcal urethritis. Br. J. Vener. Dis. 48: 437 444. PubMed
55. Rustad, T. R.,, M. I. Harrell,, R. Liao,, and D. R. Sherman. 2008. The enduring hypoxic response of Mycobacterium tuberculosis. PLoS One 3: e1502. PubMed CrossRef
56. Schoborg, R. V. 2011. Chlamydia persistence—a tool to dissect Chlamydia-host cell interactions. Microbes Infect. 13: 649 662. PubMed CrossRef
57. Shaw, A. C.,, G. Christiansen,, P. Roepstorff,, and S. Birkelund. 2000. Genetic differences in the Chlamydia trachomatis tryptophan synthase a-subunit can explain variations in serovar pathogenesis. Microbes Infect. 2: 581 592. PubMed
58. Shleeva, M. O.,, G. V. Mukamolova,, M. Young,, H. D. Williams,, and A. S. Kaprelyants. 2004. Formation of “non-culturable” cells of Mycobacterium smegmatis in stationary phase in response to growth under suboptimal conditions and their Rpf-mediated resuscitation. Microbiology 150: 1687 1697. PubMed CrossRef
59. Singh, A. E.,, and B. Romanowski. 1999. Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. Clin. Microbiol. Rev. 12: 187 209. PubMed
60. Sinnott, C. R.,, and A. J. Teall. 1987. Persistent gallbladder carriage of Salmonella typhi. Lancet i: 976. PubMed CrossRef
61. Soete, M.,, D. Camus,, and J. F. Dubremetz. 1994. Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. Exp. Parasitol. 78: 361 370. PubMed
62. Song, Z.,, P. Brassard,, and J. M. Brophy. 2008. A meta-analysis of antibiotic use for the secondary prevention of cardiovascular diseases. Can. J. Cardiol. 24: 391 395. PubMed
63. Stern, L. C. 1875. Papyros Ebers: Das hermetische Buch uber die Arzeneimittel der alten Agypter in hieratischer Schrift, herausgegeben mit Inhaltsangabe und Einleitung versehen von Georg Ebers, mit Heiroglyphisch-Lateinischem Gloisser von Ludwig Stern, mit Unterstutzung des Koniglich Sachsischen Cultusministerium, 2. G Ebers ed., Leipzig, Germany.
64. Sullivan, W. J., Jr.,, A. T. Smith,, and B. R. Joyce. 2009. Understanding mechanisms of differentiation and a role in the pathogenesis of Toxoplasma gondii: a review. Mem. Inst. Oswaldo Cruz 104: 155 161. PubMed
65. Tan, C.,, R.-C. Hsia,, H. Shou,, C. Haggerty,, C. Gaydos,, D. Dean,, A. Scurlock,, D. P. Wilson,, and P. M. Bavoil. 2009. Chlamydia trachomatis-infected patients display variable antibody profiles against the nine-member polymorphic membrane protein family. Infect. Immun. 77: 3218 3226. PubMed CrossRef
66. Taylor, H. R. 2008. Trachoma, a Blinding Scourge from the Bronze Age to the Twenty-First Century. Haddington Press, South Yarra, Australia.
67. Townes, J. M. 2010. Reactive arthritis after enteric infections in the United States: the problem of definition. Clin. Infect. Dis. 50: 247 254.
68. Voskuil, M. I.,, K. C. Visconti,, and G. K. Schoolnik. 2004. Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy. Tuberculosis 84: 218 227. PubMed CrossRef
69. Watson, C.,, and N. J. Alp. 2008. Role of Chlamydia pneumoniae in atherosclerosis. Clin. Sci. 114: 509 531. PubMed CrossRef
70. Wayne, L. G.,, and C. D. Sohaskey. 2001. Nonreplicating persistence of Mycobacterium tuberculosis. Annu. Rev. Microbiol. 55: 139 163. PubMed CrossRef
71. Weiss, L. M.,, and K. Kim. 2000. The development and biology of bradyzoites of Toxoplasma gondii. Front. Biosci. 5: 391 405. PubMed
72. Wells, T. N. C.,, J. N. Burrows,, and J. K. Baird. 2010. Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination. Trends Parasitol. 26: 145 151. PubMed CrossRef
73. Wilson, B. A.,, A. A. Salyers,, D. D. Whitt,, and M. E. Winkler. 2011. Bacterial Pathogenesis: a Molecular Approach, 3rd ed. ASM Press, Washington, DC.
74. Wood, H.,, C. Fehlner-Gardner,, J. Berry,, E. Fischer,, B. Graham,, T. Hackstadt,, C. Roshick,, and G. McClarty. 2003. Regulation of tryptophan synthase gene expression in Chlamydia trachomatis. Mol. Microbiol. 49: 1347 1359. PubMed CrossRef
75. Wyrick, P. B. 2010. Chlamydia persistence in vitro: an overview. J. Infect. Dis. 201(S2):S88-S95. PubMed CrossRef

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