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. 1997 Apr;10(2):320–344. doi: 10.1128/cmr.10.2.320

Bacterial persistence and expression of disease.

G J Domingue Sr 1, H B Woody 1
PMCID: PMC172922  PMID: 9105757

Abstract

A considerable body of experimental and clinical evidence supports the concept that difficult-to-culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic. This review includes details on the diverse forms and functions of individual bacteria and attempts to make this information relevant to the care of patients. A series of experimental studies involving host-bacterium interactions illustrates the probability that most bacteria exposed to a deleterious host environment can assume a form quite different from that of a free-living bacterium. A hypothesis is offered for a kind of reproductive cycle of morphologically aberrant bacteria as a means to relate their diverse tissue forms to each other. Data on the basic biology of persistent bacteria are correlated with expression of disease and particularly the mechanisms of both latency and chronicity that typify certain infections. For example, in certain streptococcal and nocardial infections, it has been clearly established that wall-defective forms can be induced in a suitable host. These organisms can survive and persist in a latent state within the host, and they can cause pathologic responses compatible with disease. A series of cases illustrating idiopathic conditions in which cryptic bacteria have been implicated in the expression of disease is presented. These conditions include nephritis, rheumatic fever, aphthous stomatitis, idiopathic hematuria, Crohn's disease, and mycobacterial infections. By utilizing PCR, previously nonculturable bacilli have been identified in patients with Whipple's disease and bacillary angiomatosis. Koch's postulates may have to be redefined in terms of molecular data when dormant and nonculturable bacteria are implicated as causative agents of mysterious diseases.

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Selected References

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  1. ALDERMAN M. H., FREEDMAN L. R. EXPERIMENTAL PYELONEPHRITIS. X. THE DIRECT INJECTION OF E. COLI PROTOPLASTS INTO THE MEDULLA OF THE RABBIT KIDNEY. Yale J Biol Med. 1963 Oct;36:157–164. [PMC free article] [PubMed] [Google Scholar]
  2. Archer G. L., Coleman P. H., Cole R. M., Duma R. J., Johnston C. L., Jr Human infection from an unidentified erythrocyte-associated bacterium. N Engl J Med. 1979 Oct 25;301(17):897–900. doi: 10.1056/NEJM197910253011701. [DOI] [PubMed] [Google Scholar]
  3. Archer G. L., Vazquez G. J., Johnston J. L. Antibiotic prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis. J Infect Dis. 1980 Nov;142(5):725–731. doi: 10.1093/infdis/142.5.725. [DOI] [PubMed] [Google Scholar]
  4. Asnani P. J., Gill K. Biological properties of L-forms and their parent bacteria. Acta Microbiol Acad Sci Hung. 1980;27(2):131–134. [PubMed] [Google Scholar]
  5. Bacigalupi B. A., Lawson J. W. Defined physiological conditions for the induction of the L-form of Neisseria gonorrhoeae. J Bacteriol. 1973 Nov;116(2):778–784. doi: 10.1128/jb.116.2.778-784.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beaman B. L. An ultrastructural analysis of Nocardia during experimental infections in mice. Infect Immun. 1973 Nov;8(5):828–840. doi: 10.1128/iai.8.5.828-840.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beaman B. L., Burnside J., Edwards B., Causey W. Nocardial infections in the United States, 1972-1974. J Infect Dis. 1976 Sep;134(3):286–289. doi: 10.1093/infdis/134.3.286. [DOI] [PubMed] [Google Scholar]
  8. Beaman B. L. In vitro response of rabbit alveolar macrophages to infection with Nocardia asteroides. Infect Immun. 1977 Mar;15(3):925–937. doi: 10.1128/iai.15.3.925-937.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beaman B. L. Induction of L-phase variants of Nocardia caviae within intact murine lungs. Infect Immun. 1980 Jul;29(1):244–251. doi: 10.1128/iai.29.1.244-251.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Beaman B. L. Interaction of Nocardia asteroides at different phases of growth with in vitro-maintained macrophages obtained from the lungs of normal and immunized rabbits. Infect Immun. 1979 Oct;26(1):355–361. doi: 10.1128/iai.26.1.355-361.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Beaman B. L., Scates S. M. Role of L-forms of Nocardia caviae in the development of chronic mycetomas in normal and immunodeficient murine models. Infect Immun. 1981 Sep;33(3):893–907. doi: 10.1128/iai.33.3.893-907.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Beaman B. L., Shankel D. M. Ultrastructure of Nocardia cell growth and development on defined and complex agar media. J Bacteriol. 1969 Sep;99(3):876–884. doi: 10.1128/jb.99.3.876-884.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Beaman B. L., Smathers M. Interaction of Nocardia asteroides with cultured rabbit alveolar macrophages. Infect Immun. 1976 Apr;13(4):1126–1131. doi: 10.1128/iai.13.4.1126-1131.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  15. Bisset K. A., Bartlett R. The isolation and characters of L-forms and reversions of Bacillus licheniformis var. Endoparasiticus (Benedek) associated with the erythrocytes of clinically normal persons. J Med Microbiol. 1978 Aug;11(3):335–349. doi: 10.1099/00222615-11-3-335. [DOI] [PubMed] [Google Scholar]
  16. Bourgeois L., Beaman B. L. In vitro spheroplast and L-form induction within the pathogenic nocardiae. J Bacteriol. 1976 Jul;127(1):584–594. doi: 10.1128/jb.127.1.584-594.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Bourgeois L., Beaman B. L. Probable L-forms of Nocardia asteroides induced in cultured mouse peritoneal macrophages. Infect Immun. 1974 Mar;9(3):576–590. doi: 10.1128/iai.9.3.576-590.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Braude A. I. Production of bladder stones by L-forms. Ann N Y Acad Sci. 1970 Oct 30;174(2):896–902. doi: 10.1111/j.1749-6632.1970.tb45609.x. [DOI] [PubMed] [Google Scholar]
  19. Cohen M., Panos C. Membrane lipid composition of Streptococcus pyogenes and derived L form. Biochemistry. 1966 Jul;5(7):2385–2392. doi: 10.1021/bi00871a031. [DOI] [PubMed] [Google Scholar]
  20. Cohen S. N., Shapiro J. A. Transposable genetic elements. Sci Am. 1980 Feb;242(2):40–49. doi: 10.1038/scientificamerican0280-40. [DOI] [PubMed] [Google Scholar]
  21. DIENES L., SHARP J. T. The role of high electrolyte concentration in the production and growth of L forms of bacteria. J Bacteriol. 1956 Feb;71(2):208–213. doi: 10.1128/jb.71.2.208-213.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. DIENES L., WEINBERGER H. J., MADOFF S. The transformation of typhoid bacilli into L forms under various conditions. J Bacteriol. 1950 Jun;59(6):755–764. doi: 10.1128/jb.59.6.755-764.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. DIENES L., WEINBERGER H. J. The L forms of bacteria. Bacteriol Rev. 1951 Dec;15(4):245–288. doi: 10.1128/br.15.4.245-288.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Demonty J. Experimental Escherichia coli pyelonephritis: formation of spheroplasts in the kidney of the untreated rat. Antonie Van Leeuwenhoek. 1970;36(2):273–284. doi: 10.1007/BF02069029. [DOI] [PubMed] [Google Scholar]
  25. Dienes L., Bullivant S. Morphology and reproductive processes of the L forms of bacteria. II. Comparative study of L forms and Mycoplasma with the electron microscope. J Bacteriol. 1968 Feb;95(2):672–687. doi: 10.1128/jb.95.2.672-687.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Dienes L. Morphology and reproductive processes of the L forms of bacteria. I. Streptococci and staphylocci. J Bacteriol. 1967 Feb;93(2):693–702. doi: 10.1128/jb.93.2.693-702.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Dienes L. Nomenclature of bacterial L-forms and cell wall-defective bacteria. J Infect Dis. 1973 Apr;127(4):476–477. doi: 10.1093/infdis/127.4.476. [DOI] [PubMed] [Google Scholar]
  28. Dienes L., Pachas W. N. Observations suggesting the development of streptococci from pleomorphic filamentous gram negative bacteria. Yale J Biol Med. 1971 Jun;43(6):337–350. [PMC free article] [PubMed] [Google Scholar]
  29. Dienes L. Permanent alterations of the L-forms of proteus and salmonella under various conditions. J Bacteriol. 1970 Dec;104(3):1369–1377. doi: 10.1128/jb.104.3.1369-1377.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Dienes L. Permanent stained agar preparation of Mycoplasma and of L forms of bacteria. J Bacteriol. 1967 Feb;93(2):689–692. doi: 10.1128/jb.93.2.689-692.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Dienes L. The Isolation of L Type Cultures from Bacteroides with the Aid of Penicillin and Their Reversion into the Usual Bacilli. J Bacteriol. 1948 Oct;56(4):445–456. doi: 10.1128/jb.56.4.445-456.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Dobbins W. O., 3rd, Kawanishi H. Bacillary characteristics in Whipple's disease: an electron microscopic study. Gastroenterology. 1981 Jun;80(6):1468–1475. [PubMed] [Google Scholar]
  33. Domingue G. J. Filterable cell-associated cryptic bacterial forms in immunologic renal diseases. Urol Surv. 1980 Feb;30(1):1–4. [PubMed] [Google Scholar]
  34. Domingue G. J., Ghoniem G. M., Bost K. L., Fermin C., Human L. G. Dormant microbes in interstitial cystitis. J Urol. 1995 Apr;153(4):1321–1326. [PubMed] [Google Scholar]
  35. Domingue G. J., Schlegel J. U. Novel bacterial structures in human blood. II. Bacterial variants as etiologic agents in idiopathic hematuria. J Urol. 1978 Dec;120(6):708–711. doi: 10.1016/s0022-5347(17)57337-1. [DOI] [PubMed] [Google Scholar]
  36. Domingue G. J., Schlegel J. U. Novel bacterial structures in human blood: cultural isolation. Infect Immun. 1977 Feb;15(2):621–627. doi: 10.1128/iai.15.2.621-627.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Domingue G. J., Schlegel J. U. The possible role of microbial L-forms in pyelonephritis. J Urol. 1970 Dec;104(6):790–798. doi: 10.1016/s0022-5347(17)61838-x. [DOI] [PubMed] [Google Scholar]
  38. Domingue G. J., Thomas R., Walters F., Serrano A., Heidger P. M., Jr Cell wall deficient bacteria as a cause of idiopathic hematuria. J Urol. 1993 Aug;150(2 Pt 1):483–485. doi: 10.1016/s0022-5347(17)35523-4. [DOI] [PubMed] [Google Scholar]
  39. Domingue G. J., Woody H. B., Farris K. B., Schlegel J. U. Bacterial variants in urinary casts and renal epithelial cells. Arch Intern Med. 1979 Dec;139(12):1355–1360. [PubMed] [Google Scholar]
  40. Domingue G., Lloyd K., Schlegel J. U. In vitro phagocytosis of transitional phase bacterial variants utilizing autoradiography. Proc Soc Exp Biol Med. 1974 Jun;146(2):635–642. doi: 10.3181/00379727-146-38162. [DOI] [PubMed] [Google Scholar]
  41. Domingue G., Turner B., Schlegel J. U. Cell-wall deficient bacterial variants in kidney tissue. Detection by immunofluorescence. Urology. 1974 Mar;3(3):288–292. doi: 10.1016/s0090-4295(74)80105-6. [DOI] [PubMed] [Google Scholar]
  42. Eda T., Kanda Y., Kimura S. Membrane structures in stable L-forms of Escherichia coli. J Bacteriol. 1976 Sep;127(3):1564–1567. doi: 10.1128/jb.127.3.1564-1567.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Eisenstein B. I. New opportunistic infections--more opportunities. N Engl J Med. 1990 Dec 6;323(23):1625–1627. doi: 10.1056/NEJM199012063232309. [DOI] [PubMed] [Google Scholar]
  44. Feinman S. B., Prescott B., Cole R. M. Serological reactions of glycolipids from streptococcal L-forms. Infect Immun. 1973 Nov;8(5):752–756. doi: 10.1128/iai.8.5.752-756.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Fleming J. L., Wiesner R. H., Shorter R. G. Whipple's disease: clinical, biochemical, and histopathologic features and assessment of treatment in 29 patients. Mayo Clin Proc. 1988 Jun;63(6):539–551. doi: 10.1016/s0025-6196(12)64884-8. [DOI] [PubMed] [Google Scholar]
  46. Gilpin R. W., Young F. E., Chatterjee A. N. Characterization of a stable L-form of Bacillus subtilis 168. J Bacteriol. 1973 Jan;113(1):486–499. doi: 10.1128/jb.113.1.486-499.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Green M. T., Heidger P. M., Jr, Domingue G. Demonstration of the phenomena of microbial persistence and reversion with bacterial L-forms in human embryonic kidney cells. Infect Immun. 1974 Oct;10(4):889–914. doi: 10.1128/iai.10.4.889-914.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Green M. T., Heidger P. M., Jr, Domingue G. Proposed reproductive cycle for a relatively stable L-phase variant of Streptococcus faecalis. Infect Immun. 1974 Oct;10(4):915–927. doi: 10.1128/iai.10.4.915-927.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Gregory W. W., Gooder H. Inhibition of peptidoglycan biosynthesis at a postcytoplasmic reaction in a stable L-phase variant of Streptococcus faecium. J Bacteriol. 1978 Sep;135(3):900–910. doi: 10.1128/jb.135.3.900-910.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Guerrero R., Ashen J., Sole M., Margulis L. Spirosymplokos deltaeiberi nov. gen., nov. sp.: variable-diameter composite spirochete from microbial mats. Arch Microbiol. 1993;160:461–470. doi: 10.1007/BF00245307. [DOI] [PubMed] [Google Scholar]
  51. Gutman L. T., Turck M., Petersdorf R. G., Wedgwood R. J. Significance of bacterial variants in urine of patients with chronic bacteriuria. J Clin Invest. 1965 Dec;44(12):1945–1952. doi: 10.1172/JCI105300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Guze L. B., Harwick H. J., Kalmanson G. M. Klebsiella L-forms: effect of growth as L-form on virulence of reverted Klebsiella pneumoniae. J Infect Dis. 1976 Mar;133(3):245–252. doi: 10.1093/infdis/133.3.245. [DOI] [PubMed] [Google Scholar]
  53. HIJMANS W. Absence of the group-specific and the cell-wall polysaccharide antigen in L-phase variants of group D streptococci. J Gen Microbiol. 1962 Apr;28:177–179. doi: 10.1099/00221287-28-1-177. [DOI] [PubMed] [Google Scholar]
  54. HIJMANS W., DIENES L. Further observations on L forms of alpha-hemolytic Streptococci. Proc Soc Exp Biol Med. 1955 Dec;90(3):672–675. doi: 10.3181/00379727-90-22133. [DOI] [PubMed] [Google Scholar]
  55. Hatten B. A., Sulkin S. E. Intracellular Production of Brucella L Forms I. Recovery of L Forms from Tissue Culture Cells Infected with Brucella abortus. J Bacteriol. 1966 Jan;91(1):285–296. doi: 10.1128/jb.91.1.285-296.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Hatten B. A., Sulkin S. E. Intracellular production of Brucella L forms . II. Induction and survival of Brucella abortus L forms in tissue culture. J Bacteriol. 1966 Jan;91(1):14–20. doi: 10.1128/jb.91.1.14-20.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Horne D., Hakenbeck R., Tomasz A. Secretion of lipids induced by inhibition of peptidoglycan synthesis in streptococci. J Bacteriol. 1977 Nov;132(2):704–717. doi: 10.1128/jb.132.2.704-717.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Hoyer B. H., King J. R. Deoxyribonucleic acid sequence losses in a stable streptococcal L form. J Bacteriol. 1969 Mar;97(3):1516–1517. doi: 10.1128/jb.97.3.1516-1517.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Hubert E. G., Potter C. S., Hensley T. J., Cohen M., Kalmanson G. M., Guze L. B. L-forms of Pseudomonas aeruginosa. Infect Immun. 1971 Jul;4(1):60–72. doi: 10.1128/iai.4.1.60-72.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Kagan G. Ia, Shmitt-Slomska Zh I., Koptelova E. I., Chumachenko N. V., Rakovskaia I. V. Eksperimental'naia infektsiia u obez'ian, vyzvannaia L-formami steptokokka ruppa A. II. Ostraia éksperimental'naia infektsiia u obez'ian. Zh Mikrobiol Epidemiol Immunobiol. 1972 Feb;49(2):107–112. [PubMed] [Google Scholar]
  61. Keinath R. D., Merrell D. E., Vlietstra R., Dobbins W. O., 3rd Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology. 1985 Jun;88(6):1867–1873. doi: 10.1016/0016-5085(85)90012-5. [DOI] [PubMed] [Google Scholar]
  62. Keusch G. T. Specific membrane receptors: pathogenetic and therapeutic implications in infectious diseases. Rev Infect Dis. 1979 May-Jun;1(3):517–529. doi: 10.1093/clinids/1.3.517. [DOI] [PubMed] [Google Scholar]
  63. King J. R., Gooder H. Induction of enterococcal L-forms by the action of lysozyme. J Bacteriol. 1970 Sep;103(3):686–691. doi: 10.1128/jb.103.3.686-691.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. King J. R., Gooder H. Reversion to the streptococcal state of enterococcal protoplasts, spheroplasts, and L-forms. J Bacteriol. 1970 Sep;103(3):692–696. doi: 10.1128/jb.103.3.692-696.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. King J. R., Prescott B., Caldes G. Lack of murein in a formamide-insoluble fraction from the stable L-form of Streptococcus faecium. J Bacteriol. 1970 Apr;102(1):196–197. [PMC free article] [PubMed] [Google Scholar]
  66. King J. R., Theodore T. S., Cole R. M. Generic identification of L-forms by polyacrylamide gel electrophoretic comparison of extracts from parent strains and their derived L-forms. J Bacteriol. 1969 Oct;100(1):71–77. doi: 10.1128/jb.100.1.71-77.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Kirsner J. B., Shorter R. G. Recent developments in "nonspecific" inflammatory bowel disease (first of two parts). N Engl J Med. 1982 Apr 1;306(13):775–785. doi: 10.1056/NEJM198204013061304. [DOI] [PubMed] [Google Scholar]
  68. Kirsner J. B., Shorter R. G. Recent developments in nonspecific inflammatory bowel disease (second of two parts). N Engl J Med. 1982 Apr 8;306(14):837–848. doi: 10.1056/NEJM198204083061404. [DOI] [PubMed] [Google Scholar]
  69. LANDMAN O. E., HALLE S. ENZYMICALLY AND PHYSICALLY INDUCED INHERITANCE CHANGES IN BACILLUS SUBTILIS. J Mol Biol. 1963 Dec;7:721–738. doi: 10.1016/s0022-2836(63)80119-9. [DOI] [PubMed] [Google Scholar]
  70. LEDERBERG J., ST CLAIR J. Protoplasts and L-type growth of Escherichia coli. J Bacteriol. 1958 Feb;75(2):143–160. doi: 10.1128/jb.75.2.143-160.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Landman O. E., Forman A. Gelatin-induced reversion of protoplasts of Bacillus subtilis to the bacillary form: biosynthesis of macromolecules and wall during successive steps. J Bacteriol. 1969 Aug;99(2):576–589. doi: 10.1128/jb.99.2.576-589.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Landman O. E., Ryter A., Fréhel C. Gelatin-induced reversion of protoplasts of Bacillus subtilis to the bacillary form: electron-microscopic and physical study. J Bacteriol. 1968 Dec;96(6):2154–2170. doi: 10.1128/jb.96.6.2154-2170.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Leon O., Panos C. Adaptation of an osmotically fragile L-form of Streptococcus pyogenes to physiological osmotic conditions and its ability to destroy human heart cells in tissue culture. Infect Immun. 1976 Jan;13(1):252–262. doi: 10.1128/iai.13.1.252-262.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Lucy J. A. The fusion of biological membranes. Nature. 1970 Aug 22;227(5260):815–817. doi: 10.1038/227815a0. [DOI] [PubMed] [Google Scholar]
  75. MADOFF M. A., ANNENBERG S. M., WEINSTEIN L. Production of neuraminidase by L forms of Vibrio cholerae. Proc Soc Exp Biol Med. 1961 Aug-Sep;107:776–777. doi: 10.3181/00379727-107-26751. [DOI] [PubMed] [Google Scholar]
  76. MADOFF S., DIENES L. L forms from pneumococci. J Bacteriol. 1958 Sep;76(3):245–250. doi: 10.1128/jb.76.3.245-250.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. MADOFF S. Isolation and identification of PPLO. Ann N Y Acad Sci. 1960 Jan 15;79:383–392. doi: 10.1111/j.1749-6632.1960.tb42702.x. [DOI] [PubMed] [Google Scholar]
  78. MATTMAN L. H., TUNSTALL L. H., ROSSMOORE H. W. Induction and characteristics of staphylococcal L forms. Can J Microbiol. 1961 Oct;7:705–713. doi: 10.1139/m61-084. [DOI] [PubMed] [Google Scholar]
  79. Mackowiak P. A. Microbial synergism in human infections (first of two parts). N Engl J Med. 1978 Jan 5;298(1):21–26. doi: 10.1056/NEJM197801052980105. [DOI] [PubMed] [Google Scholar]
  80. Mackowiak P. A. Microbial synergism in human infections (second of two parts). N Engl J Med. 1978 Jan 12;298(2):83–87. doi: 10.1056/NEJM197801122980206. [DOI] [PubMed] [Google Scholar]
  81. Madoff S., Burke M. E., Dienes L. Induction and identification of L-forms of bacteria. Ann N Y Acad Sci. 1967 Jul 28;143(1):755–759. doi: 10.1111/j.1749-6632.1967.tb27722.x. [DOI] [PubMed] [Google Scholar]
  82. Madoff S. Mycoplasma and L-forms: occurrence in bacterial cultures. Health Lab Sci. 1976 Apr;13(2):159–166. [PubMed] [Google Scholar]
  83. Margulis L., Ashen J. B., Solé M., Guerrero R. Composite, large spirochetes from microbial mats: spirochete structure review. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6966–6970. doi: 10.1073/pnas.90.15.6966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. McDonald P. J., Wetherall B. L., Pruul H. Postantibiotic leukocyte enhancement: increased susceptibility of bacteria pretreated with antibiotics to activity of leukocytes. Rev Infect Dis. 1981 Jan-Feb;3(1):38–44. doi: 10.1093/clinids/3.1.38. [DOI] [PubMed] [Google Scholar]
  85. McGee Z. A., Wittler R. G., Gooder H., Charache P. Wall-defective microbial variants: terminology and experimental design. J Infect Dis. 1971 Apr;123(4):433–438. doi: 10.1093/infdis/123.4.433. [DOI] [PubMed] [Google Scholar]
  86. Moss A. A., Carbone J. V., Kressel H. Y. Radiologic and clinical assessment of broad-spectrum antibiotic therapy in Crohn's disease. AJR Am J Roentgenol. 1978 Nov;131(5):787–790. doi: 10.2214/ajr.131.5.787. [DOI] [PubMed] [Google Scholar]
  87. NELSON E. L. The development in vitro of particles from cytoplasm. I. Observations on particle development in bacteriologic media. J Exp Med. 1958 May 1;107(5):755–768. doi: 10.1084/jem.107.5.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Neimark H., London J. Origins of the mycoplasmas: sterol-nonrequiring mycoplasmas evolved from streptococci. J Bacteriol. 1982 Jun;150(3):1259–1265. doi: 10.1128/jb.150.3.1259-1265.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Noordhoek G. T., Wolters E. C., de Jonge M. E., van Embden J. D. Detection by polymerase chain reaction of Treponema pallidum DNA in cerebrospinal fluid from neurosyphilis patients before and after antibiotic treatment. J Clin Microbiol. 1991 Sep;29(9):1976–1984. doi: 10.1128/jcm.29.9.1976-1984.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Ooi B. S., Cohen D. J. Host immune deficiency in immune complex nephritis. J Am Soc Nephrol. 1995 Nov;6(5):1342–1346. doi: 10.1681/ASN.V651342. [DOI] [PubMed] [Google Scholar]
  91. Parent K., Mitchell P. D. Bacterial variants: etiologic agent in Crohn's disease? Gastroenterology. 1976 Aug;71(2):365–368. [PubMed] [Google Scholar]
  92. Piepkorn M. W., Reichenbach D. D. Infective endocarditis associated with cell wall-deficient bacteria. Electron microscopic findings in four cases. Hum Pathol. 1978 Mar;9(2):163–173. doi: 10.1016/s0046-8177(78)80107-5. [DOI] [PubMed] [Google Scholar]
  93. Ponig B., Domingue G., Schlegel J. The role of in vitro induced microbial L-forms in experimental hematogenous pyelonephritis. Invest Urol. 1972 Jan;9(4):282–285. [PubMed] [Google Scholar]
  94. Relman D. A., Loutit J. S., Schmidt T. M., Falkow S., Tompkins L. S. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N Engl J Med. 1990 Dec 6;323(23):1573–1580. doi: 10.1056/NEJM199012063232301. [DOI] [PubMed] [Google Scholar]
  95. Relman D. A., Schmidt T. M., MacDermott R. P., Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30;327(5):293–301. doi: 10.1056/NEJM199207303270501. [DOI] [PubMed] [Google Scholar]
  96. Rogers M. J., Simmons J., Walker R. T., Weisburg W. G., Woese C. R., Tanner R. S., Robinson I. M., Stahl D. A., Olsen G., Leach R. H. Construction of the mycoplasma evolutionary tree from 5S rRNA sequence data. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1160–1164. doi: 10.1073/pnas.82.4.1160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Rook G. A., Stanford J. L. Slow bacterial infections or autoimmunity? Immunol Today. 1992 May;13(5):160–164. doi: 10.1016/0167-5699(92)90119-R. [DOI] [PubMed] [Google Scholar]
  98. SHARP J. T., HIJMANS W., DIENES L. Examination of the L forms of group A streptococci for the group-specific polysaccharide and M protein. J Exp Med. 1957 Feb 1;105(2):153–159. doi: 10.1084/jem.105.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. SHARP J. T. L Colonies from hemolytic streptocci: new technic in the study of L forms of bacteria. Proc Soc Exp Biol Med. 1954 Oct;87(1):94–97. doi: 10.3181/00379727-87-21297. [DOI] [PubMed] [Google Scholar]
  100. Schifferli J. A., Ng Y. C., Peters D. K. The role of complement and its receptor in the elimination of immune complexes. N Engl J Med. 1986 Aug 21;315(8):488–495. doi: 10.1056/NEJM198608213150805. [DOI] [PubMed] [Google Scholar]
  101. Schmitt-Slomska J., Boué A., Caravano R. Induction of L-variants in human diploid cells infected by group A streptococci. Infect Immun. 1972 Mar;5(3):389–399. doi: 10.1128/iai.5.3.389-399.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Schmitt-Slomska J., Caravano R., Anoal M., Gay B., Roux J. Isolation of L-forms from the spleens of Brucella suis-infected, penicillin-treated mice. Ann Microbiol (Paris) 1981 May-Jun;132(3):253–265. [PubMed] [Google Scholar]
  103. Schmitt-Slomska J., Drach G., Caravano R. Incidence of cellular and humoral factors on group A streptococcal L forms. I. Microscopic study of the association of L forms with human polymorphonuclear leucocytes and mouse peritoneal macrophages. Ann Microbiol (Paris) 1973 Oct;124(3):329–350. [PubMed] [Google Scholar]
  104. Schmitt-Slomska J., Lucel-Varnier Y. Essai d'isolement de bactéries en phase L chez des souris inoculées avec des streptocoques du groupe A et traitées par la pénicilline. Ann Inst Pasteur (Paris) 1969 Sep;117(3):347–363. [PubMed] [Google Scholar]
  105. Schnaper H. W. The immune system in minimal change nephrotic syndrome. Pediatr Nephrol. 1989 Jan;3(1):101–110. doi: 10.1007/BF00859637. [DOI] [PubMed] [Google Scholar]
  106. Small P. L., Ramakrishnan L., Falkow S. Remodeling schemes of intracellular pathogens. Science. 1994 Feb 4;263(5147):637–639. doi: 10.1126/science.8303269. [DOI] [PubMed] [Google Scholar]
  107. Unanue E. R., Allen P. M. The immunoregulatory role of the macrophage. Hosp Pract (Off Ed) 1987 Apr 15;22(4):87-98, 102-4. doi: 10.1080/21548331.1987.11707695. [DOI] [PubMed] [Google Scholar]
  108. Van Boven C. P., Kastelein M. J., Hijmans W. A chemically defined medium for the L-phase of group A streptococci. Ann N Y Acad Sci. 1967 Jul 28;143(1):749–754. doi: 10.1111/j.1749-6632.1967.tb27721.x. [DOI] [PubMed] [Google Scholar]
  109. Winterbauer R. H., Gutman L. T., Turck M., Wedgwood R. J., Petersdorf R. G. The role of penicillin-induced bacterial variants in experimental pyelonephritis. J Exp Med. 1967 Apr 1;125(4):607–618. doi: 10.1084/jem.125.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Wyrick P. B., McConnell M., Rogers H. J. Genetic transfer of the stable L form state to intact bacterial cells. Nature. 1973 Aug 24;244(5417):505–507. doi: 10.1038/244505a0. [DOI] [PubMed] [Google Scholar]
  111. Wyrick P. B., Rogers H. J. Isolation and characterization of cell wall-defective variants of Bacillus subtilis and Bacillus licheniformis. J Bacteriol. 1973 Oct;116(1):456–465. doi: 10.1128/jb.116.1.456-465.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]

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