Search tips
Search criteria 


Logo of cmrPermissionsJournals.ASM.orgJournalCMR ArticleJournal InfoAuthorsReviewers
Clin Microbiol Rev. 1996 January; 9(1): 18–33.
PMCID: PMC172879

Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates.


Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch's postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch's postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch's original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple's disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi's sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.

Full Text

The Full Text of this article is available as a PDF (482K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Amann RI, Ludwig W, Schleifer KH. Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev. 1995 Mar;59(1):143–169. [PMC free article] [PubMed]
  • Anderson BE, Dawson JE, Jones DC, Wilson KH. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J Clin Microbiol. 1991 Dec;29(12):2838–2842. [PMC free article] [PubMed]
  • Anderson BE, Sumner JW, Dawson JE, Tzianabos T, Greene CR, Olson JG, Fishbein DB, Olsen-Rasmussen M, Holloway BP, George EH, et al. Detection of the etiologic agent of human ehrlichiosis by polymerase chain reaction. J Clin Microbiol. 1992 Apr;30(4):775–780. [PMC free article] [PubMed]
  • Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging? JAMA. 1994 Jul 20;272(3):212–218. [PubMed]
  • Böddinghaus B, Rogall T, Flohr T, Blöcker H, Böttger EC. Detection and identification of mycobacteria by amplification of rRNA. J Clin Microbiol. 1990 Aug;28(8):1751–1759. [PMC free article] [PubMed]
  • Böttger EC. Rapid determination of bacterial ribosomal RNA sequences by direct sequencing of enzymatically amplified DNA. FEMS Microbiol Lett. 1989 Nov;53(1-2):171–176. [PubMed]
  • Böttger EC, Teske A, Kirschner P, Bost S, Chang HR, Beer V, Hirschel B. Disseminated "Mycobacterium genavense" infection in patients with AIDS. Lancet. 1992 Jul 11;340(8811):76–80. [PubMed]
  • Brown MS, Goldstein JL. Koch's postulates for cholesterol. Cell. 1992 Oct 16;71(2):187–188. [PubMed]
  • Butler JC, Peters CJ. Hantaviruses and hantavirus pulmonary syndrome. Clin Infect Dis. 1994 Sep;19(3):387–395. [PubMed]
  • Carter KC. Koch's postulates in relation to the work of Jacob Henle and Edwin Klebs. Med Hist. 1985 Oct;29(4):353–374. [PMC free article] [PubMed]
  • Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865–1869. [PubMed]
  • Chapman LE, Khabbaz RF. Etiology and epidemiology of the Four Corners hantavirus outbreak. Infect Agents Dis. 1994 Oct;3(5):234–244. [PubMed]
  • CHEARS WC, Jr, ASHWORTH CT. Electron microscopic study of the intestinal mucosa in Whipple's disease. Demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology. 1961 Aug;41:129–138. [PubMed]
  • Chellappan S, Kraus VB, Kroger B, Munger K, Howley PM, Phelps WC, Nevins JR. Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4549–4553. [PubMed]
  • Chen K, Neimark H, Rumore P, Steinman CR. Broad range DNA probes for detecting and amplifying eubacterial nucleic acids. FEMS Microbiol Lett. 1989 Jan 1;48(1):19–24. [PubMed]
  • Chen SM, Dumler JS, Bakken JS, Walker DH. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J Clin Microbiol. 1994 Mar;32(3):589–595. [PMC free article] [PubMed]
  • Chiodini RJ. Crohn's disease and the mycobacterioses: a review and comparison of two disease entities. Clin Microbiol Rev. 1989 Jan;2(1):90–117. [PMC free article] [PubMed]
  • Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. [PubMed]
  • Craig EA, Weissman JS, Horwich AL. Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell. Cell. 1994 Aug 12;78(3):365–372. [PubMed]
  • Dawson JE, Anderson BE, Fishbein DB, Sanchez JL, Goldsmith CS, Wilson KH, Duntley CW. Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis. J Clin Microbiol. 1991 Dec;29(12):2741–2745. [PMC free article] [PubMed]
  • Dell'Isola B, Poyart C, Goulet O, Mougenot JF, Sadoun-Journo E, Brousse N, Schmitz J, Ricour C, Berche P. Detection of Mycobacterium paratuberculosis by polymerase chain reaction in children with Crohn's disease. J Infect Dis. 1994 Feb;169(2):449–451. [PubMed]
  • Distel DL, DeLong EF, Waterbury JB. Phylogenetic characterization and in situ localization of the bacterial symbiont of shipworms (Teredinidae: Bivalvia) by using 16S rRNA sequence analysis and oligodeoxynucleotide probe hybridization. Appl Environ Microbiol. 1991 Aug;57(8):2376–2382. [PMC free article] [PubMed]
  • Dobbins WO, 3rd, Kawanishi H. Bacillary characteristics in Whipple's disease: an electron microscopic study. Gastroenterology. 1981 Jun;80(6):1468–1475. [PubMed]
  • Donham KJ, Thorne PS. Agents in organic dust: criteria for a causal relationship. Am J Ind Med. 1994 Jan;25(1):33–39. [PubMed]
  • Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, Ksiazek TG, Rollin PE, Nichol S, Umland ET, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group. N Engl J Med. 1994 Apr 7;330(14):949–955. [PubMed]
  • Edberg SC. Principles of nucleic acid hybridization and comparison with monoclonal antibody technology for the diagnosis of infectious diseases. Yale J Biol Med. 1985 Sep-Oct;58(5):425–442. [PMC free article] [PubMed]
  • Elliott LH, Ksiazek TG, Rollin PE, Spiropoulou CF, Morzunov S, Monroe M, Goldsmith CS, Humphrey CD, Zaki SR, Krebs JW, et al. Isolation of the causative agent of hantavirus pulmonary syndrome. Am J Trop Med Hyg. 1994 Jul;51(1):102–108. [PubMed]
  • Evans AS. Causation and disease: the Henle-Koch postulates revisited. Yale J Biol Med. 1976 May;49(2):175–195. [PMC free article] [PubMed]
  • Evans AS. Limitation of Koch's postulates. Lancet. 1977 Dec 17;2(8051):1277–1278. [PubMed]
  • Everett ED, Evans KA, Henry RB, McDonald G. Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction. Ann Intern Med. 1994 May 1;120(9):730–735. [PubMed]
  • Falkow S. Molecular Koch's postulates applied to microbial pathogenicity. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S274–S276. [PubMed]
  • Farci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991 Jul 11;325(2):98–104. [PubMed]
  • Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med. 1994 May 1;120(9):736–743. [PubMed]
  • Giovannoni SJ, Britschgi TB, Moyer CL, Field KG. Genetic diversity in Sargasso Sea bacterioplankton. Nature. 1990 May 3;345(6270):60–63. [PubMed]
  • Giovannoni SJ, DeLong EF, Olsen GJ, Pace NR. Phylogenetic group-specific oligodeoxynucleotide probes for identification of single microbial cells. J Bacteriol. 1988 Feb;170(2):720–726. [PMC free article] [PubMed]
  • Gold T. The deep, hot biosphere. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6045–6049. [PubMed]
  • Gupta RS, Golding GB. Evolution of HSP70 gene and its implications regarding relationships between archaebacteria, eubacteria, and eukaryotes. J Mol Evol. 1993 Dec;37(6):573–582. [PubMed]
  • Haase AT, Retzel EF, Staskus KA. Amplification and detection of lentiviral DNA inside cells. Proc Natl Acad Sci U S A. 1990 Jul;87(13):4971–4975. [PubMed]
  • Hackney JD, Linn WS. Koch's postulates updated: a potentially useful application to laboratory research and policy analysis in environmental toxicology. Am Rev Respir Dis. 1979 Jun;119(6):849–852. [PubMed]
  • Hall PA, Lemoine NR. Koch's postulates revisited. J Pathol. 1991 Aug;164(4):283–284. [PubMed]
  • Hanson RP. Koch is dead. J Wildl Dis. 1988 Apr;24(2):193–200. [PubMed]
  • Henle G, Henle W, Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan;59(1):94–101. [PubMed]
  • HILL AB. THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION? Proc R Soc Med. 1965 May;58:295–300. [PMC free article] [PubMed]
  • Hjelle B, Spiropoulou CF, Torrez-Martinez N, Morzunov S, Peters CJ, Nichol ST. Detection of Muerto Canyon virus RNA in peripheral blood mononuclear cells from patients with hantavirus pulmonary syndrome. J Infect Dis. 1994 Oct;170(4):1013–1017. [PubMed]
  • HUEBNER RJ. Criteria for etiologic association of prevalent viruses with prevalent diseases; the virologist's dilemma. Ann N Y Acad Sci. 1957 Apr 19;67(8):430–438. [PubMed]
  • Hughes MS, Beck LA, Skuce RA. Identification and elimination of DNA sequences in Taq DNA polymerase. J Clin Microbiol. 1994 Aug;32(8):2007–2008. [PMC free article] [PubMed]
  • Johnson RT, Gibbs CJ. Editorial: Koch's postulates and slow infections of the nervous system. Arch Neurol. 1974 Jan;30(1):36–38. [PubMed]
  • Kaneshima H, Su L, Bonyhadi ML, Connor RI, Ho DD, McCune JM. Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse. J Virol. 1994 Dec;68(12):8188–8192. [PMC free article] [PubMed]
  • Koehler JE, Quinn FD, Berger TG, LeBoit PE, Tappero JW. Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med. 1992 Dec 3;327(23):1625–1631. [PubMed]
  • Krawczynski K, Beach MJ, Bradley DW, Kuo G, di Bisceglie AM, Houghton M, Reyes GR, Kim JP, Choo QL, Alter MJ. Hepatitis C virus antigen in hepatocytes: immunomorphologic detection and identification. Gastroenterology. 1992 Aug;103(2):622–629. [PubMed]
  • Kreider JW, Howett MK, Wolfe SA, Bartlett GL, Zaino RJ, Sedlacek T, Mortel R. Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata. Nature. 1985 Oct 17;317(6038):639–641. [PubMed]
  • Ksiazek TG, Peters CJ, Rollin PE, Zaki S, Nichol S, Spiropoulou C, Morzunov S, Feldmann H, Sanchez A, Khan AS, et al. Identification of a new North American hantavirus that causes acute pulmonary insufficiency. Am J Trop Med Hyg. 1995 Feb;52(2):117–123. [PubMed]
  • Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. [PubMed]
  • Kwok S, Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. [PubMed]
  • Lakhani SR. Early clinical pathologists: Robert Koch (1843-1910). J Clin Pathol. 1993 Jul;46(7):596–598. [PMC free article] [PubMed]
  • Lane DJ, Pace B, Olsen GJ, Stahl DA, Sogin ML, Pace NR. Rapid determination of 16S ribosomal RNA sequences for phylogenetic analyses. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6955–6959. [PubMed]
  • Liesack W, Stackebrandt E. Occurrence of novel groups of the domain Bacteria as revealed by analysis of genetic material isolated from an Australian terrestrial environment. J Bacteriol. 1992 Aug;174(15):5072–5078. [PMC free article] [PubMed]
  • Lisitsyn N, Lisitsyn N, Wigler M. Cloning the differences between two complex genomes. Science. 1993 Feb 12;259(5097):946–951. [PubMed]
  • Lucey D, Dolan MJ, Moss CW, Garcia M, Hollis DG, Wegner S, Morgan G, Almeida R, Leong D, Greisen KS, et al. Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: implication for therapy and new epidemiological associations. Clin Infect Dis. 1992 Mar;14(3):683–688. [PubMed]
  • Maeda K, Markowitz N, Hawley RC, Ristic M, Cox D, McDade JE. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med. 1987 Apr 2;316(14):853–856. [PubMed]
  • Maiwald M, Meier-Willersen HJ, Hartmann M, von Herbay A. Detection of Tropheryma whippelii DNA in a patient with AIDS. J Clin Microbiol. 1995 May;33(5):1354–1356. [PMC free article] [PubMed]
  • Malawista SE, Barthold SW, Persing DH. Fate of Borrelia burgdorferi DNA in tissues of infected mice after antibiotic treatment. J Infect Dis. 1994 Nov;170(5):1312–1316. [PubMed]
  • Marley JE, McMichael AJ. Principles behind practice. 6. Disease causation. The role of epidemiological evidence. Med J Aust. 1991 Jul 15;155(2):95–101. [PubMed]
  • McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 1988 Sep 23;241(4873):1632–1639. [PubMed]
  • Meier-Willersen HJ, Maiwald M, von Herbay A. Morbus Whipple in Assoziation mit opportunistischen Infektionen. Dtsch Med Wochenschr. 1993 Jun 11;118(23):854–860. [PubMed]
  • Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181–1185. [PubMed]
  • Müller C, Stain C, Burghuber O. Tropheryma whippelii in peripheral blood mononuclear cells and cells of pleural effusion. Lancet. 1993 Mar 13;341(8846):701–701. [PubMed]
  • Muñoz N. Is Helicobacter pylori a cause of gastric cancer? An appraisal of the seroepidemiological evidence. Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):445–451. [PubMed]
  • Murray RG, Schleifer KH. Taxonomic notes: a proposal for recording the properties of putative taxa of procaryotes. Int J Syst Bacteriol. 1994 Jan;44(1):174–176. [PubMed]
  • Nakatsuji Y, Matsumoto A, Tanaka E, Ogata H, Kiyosawa K. Detection of chronic hepatitis C virus infection by four diagnostic systems: first-generation and second-generation enzyme-linked immunosorbent assay, second-generation recombinant immunoblot assay and nested polymerase chain reaction analysis. Hepatology. 1992 Aug;16(2):300–305. [PubMed]
  • Negro F, Pacchioni D, Shimizu Y, Miller RH, Bussolati G, Purcell RH, Bonino F. Detection of intrahepatic replication of hepatitis C virus RNA by in situ hybridization and comparison with histopathology. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2247–2251. [PubMed]
  • Nichol ST, Spiropoulou CF, Morzunov S, Rollin PE, Ksiazek TG, Feldmann H, Sanchez A, Childs J, Zaki S, Peters CJ. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science. 1993 Nov 5;262(5135):914–917. [PubMed]
  • Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med. 1994 Jan 27;330(4):229–234. [PubMed]
  • Olsen GJ, Woese CR. Ribosomal RNA: a key to phylogeny. FASEB J. 1993 Jan;7(1):113–123. [PubMed]
  • Parsonnet J. Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am. 1993 Mar;22(1):89–104. [PubMed]
  • Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. [PubMed]
  • Persing DH, Rutledge BJ, Rys PN, Podzorski DS, Mitchell PD, Reed KD, Liu B, Fikrig E, Malawista SE. Target imbalance: disparity of Borrelia burgdorferi genetic material in synovial fluid from Lyme arthritis patients. J Infect Dis. 1994 Mar;169(3):668–672. [PubMed]
  • Rady PL, Yen A, Rollefson JL, Orengo I, Bruce S, Hughes TK, Tyring SK. Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients. Lancet. 1995 May 27;345(8961):1339–1340. [PubMed]
  • Rand KH, Houck H. Taq polymerase contains bacterial DNA of unknown origin. Mol Cell Probes. 1990 Dec;4(6):445–450. [PubMed]
  • Reed JA, Brigati DJ, Flynn SD, McNutt NS, Min KW, Welch DF, Slater LN. Immunocytochemical identification of Rochalimaea henselae in bacillary (epithelioid) angiomatosis, parenchymal bacillary peliosis, and persistent fever with bacteremia. Am J Surg Pathol. 1992 Jul;16(7):650–657. [PubMed]
  • Relman DA. The identification of uncultured microbial pathogens. J Infect Dis. 1993 Jul;168(1):1–8. [PubMed]
  • Relman DA, Falkow S, LeBoit PE, Perkocha LA, Min KW, Welch DF, Slater LN. The organism causing bacillary angiomatosis, peliosis hepatis, and fever and bacteremia in immunocompromised patients. N Engl J Med. 1991 May 23;324(21):1514–1514. [PubMed]
  • Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N Engl J Med. 1990 Dec 6;323(23):1573–1580. [PubMed]
  • Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30;327(5):293–301. [PubMed]
  • Rickman LS, Freeman WR, Green WR, Feldman ST, Sullivan J, Russack V, Relman DA. Brief report: uveitis caused by Tropheryma whippelii (Whipple's bacillus) N Engl J Med. 1995 Feb 9;332(6):363–366. [PubMed]
  • Rivers TM. Viruses and Koch's Postulates. J Bacteriol. 1937 Jan;33(1):1–12. [PMC free article] [PubMed]
  • Rowley AH, Wolinsky SM, Relman DA, Sambol SP, Sullivan J, Terai M, Shulman ST. Search for highly conserved viral and bacterial nucleic acid sequences corresponding to an etiologic agent of Kawasaki disease. Pediatr Res. 1994 Nov;36(5):567–571. [PubMed]
  • Rys PN, Persing DH. Preventing false positives: quantitative evaluation of three protocols for inactivation of polymerase chain reaction amplification products. J Clin Microbiol. 1993 Sep;31(9):2356–2360. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Scheffner M, Romanczuk H, Münger K, Huibregtse JM, Mietz JA, Howley PM. Functions of human papillomavirus proteins. Curr Top Microbiol Immunol. 1994;186:83–99. [PubMed]
  • Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990 Dec 21;63(6):1129–1136. [PubMed]
  • Schmidt TM, DeLong EF, Pace NR. Analysis of a marine picoplankton community by 16S rRNA gene cloning and sequencing. J Bacteriol. 1991 Jul;173(14):4371–4378. [PMC free article] [PubMed]
  • Schmidt TM, Pace B, Pace NR. Detection of DNA contamination in Taq polymerase. Biotechniques. 1991 Aug;11(2):176–177. [PubMed]
  • Schmidt TM, Relman DA. Phylogenetic identification of uncultured pathogens using ribosomal RNA sequences. Methods Enzymol. 1994;235:205–222. [PubMed]
  • Silva MT, Macedo PM, Moura Nunes JF. Ultrastructure of bacilli and the bacillary origin of the macrophagic inclusions in Whipple's disease. J Gen Microbiol. 1985 May;131(5):1001–1013. [PubMed]
  • Slater LN, Welch DF, Hensel D, Coody DW. A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia. N Engl J Med. 1990 Dec 6;323(23):1587–1593. [PubMed]
  • Stoler MH. In situ hybridization. Clin Lab Med. 1990 Mar;10(1):215–236. [PubMed]
  • Stoler MH, Broker TR. In situ hybridization detection of human papillomavirus DNAs and messenger RNAs in genital condylomas and a cervical carcinoma. Hum Pathol. 1986 Dec;17(12):1250–1258. [PubMed]
  • Ward DM, Weller R, Bateson MM. 16S rRNA sequences reveal numerous uncultured microorganisms in a natural community. Nature. 1990 May 3;345(6270):63–65. [PubMed]
  • Wilson KH, Blitchington R, Frothingham R, Wilson JA. Phylogeny of the Whipple's-disease-associated bacterium. Lancet. 1991 Aug 24;338(8765):474–475. [PubMed]
  • Wilson KH, Blitchington RB, Greene RC. Amplification of bacterial 16S ribosomal DNA with polymerase chain reaction. J Clin Microbiol. 1990 Sep;28(9):1942–1946. [PMC free article] [PubMed]
  • Woese CR. Bacterial evolution. Microbiol Rev. 1987 Jun;51(2):221–271. [PMC free article] [PubMed]
  • YARDLEY JH, HENDRIX TR. Combined electron and light microscopy in Whipple's disease. Demonstration of "bacillary bodies" in the intestine. Bull Johns Hopkins Hosp. 1961 Aug;109:80–98. [PubMed]
  • Zaki SR, Greer PW, Coffield LM, Goldsmith CS, Nolte KB, Foucar K, Feddersen RM, Zumwalt RE, Miller GL, Khan AS, et al. Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. Am J Pathol. 1995 Mar;146(3):552–579. [PubMed]
  • Zeitz PS, Butler JC, Cheek JE, Samuel MC, Childs JE, Shands LA, Turner RE, Voorhees RE, Sarisky J, Rollin PE, et al. A case-control study of hantavirus pulmonary syndrome during an outbreak in the southwestern United States. J Infect Dis. 1995 Apr;171(4):864–870. [PubMed]

Articles from Clinical Microbiology Reviews are provided here courtesy of American Society for Microbiology (ASM)