Microbe hunting.
Platforms for pathogen discovery have improved since the days of Koch and Pasteur; nonetheless, the challenges of proving causation are at least as daunting as they were in the late 1800 s. Although we will almost certainly continue to accumulate low-hanging fruit, where simple relationships will be found between the presence of a cultivatable agent and a disease, these successes will be increasingly infrequent. The future of the field rests instead in our ability to follow footprints of infectious agents that cannot be characterized using classical microbiological techniques and to develop the laboratory and computational infrastructure required to dissect complex host-microbe interactions. I have tried to refine the criteria used by Koch and successors to prove linkage to disease. These refinements are working constructs that will continue to evolve in light of new technologies, new models, and new insights. What will endure is the excitement of the chase. Happy hunting!
Lipkin
W Ian
WI
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032, USA. wil2001@columbia.edu
D001419:Bacteria / Q000302:isolation & purification; D001424:Bacterial Infections / Q000382:microbiology; D001426:Bacterial Proteins / Q000737:chemistry; D003141:Communicable Diseases / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D055432:Metabolomics / Q000379:methods; D040901:Proteomics / Q000379:methods
D001426:Bacterial Proteins
Proc Natl Acad Sci U S A. 1990 Jun;87(11):4184-8
1693432
Eur J Gastroenterol Hepatol. 2005 Aug;17(8):827-36
16003132
J Clin Virol. 2008 Oct;43(2):219-22
18674964
PLoS One. 2007 Oct 03;2(10):e966
17912345
Nucleic Acids Res. 2000 Jun 15;28(12):E63
10871386
J Infect Dis. 2007 Dec 15;196(12):1754-60
18190255
J Bacteriol. 2001 Jun;183(12):3770-83
11371542
Diagn Mol Pathol. 2006 Sep;15(3):169-73
16932073
Antimicrob Agents Chemother. 1988 Apr;32(4):492-7
2837139
Pediatr Infect Dis J. 2009 Jan;28(1):59-61
19057460
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15687-92
12429852
Science. 1985 May 10;228(4700):755-6
3922055
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1316-21
12552129
J Infect Dis. 2007 Sep 15;196(6):817-25
17703411
Am J Gastroenterol. 2000 Sep;95(9):2285-95
11007230
J Gen Virol. 2006 Oct;87(Pt 10):2827-2837
16963740
Lancet. 1998 Feb 28;351(9103):637-41
9500320
Nat Biotechnol. 1996 Mar;14(3):303-8
9630890
Antimicrob Agents Chemother. 1977 Jun;11(6):946-51
879760
Pediatr Rev. 1998 Sep;19(9):291-302
9745311
Nat Methods. 2009 Sep;6(9):647-9
19668204
BMJ. 1996 Feb 10;312(7027):335-8
8611829
Nature. 2001 Feb 22;409(6823):1092-101
11234023
Emerg Infect Dis. 2008 Jun;14(6):944-7
18507910
J Clin Microbiol. 2007 Feb;45(2):443-52
17135438
Lancet. 1997 Jan 18;349(9046):178-9
9111548
Science. 1990 Nov 30;250(4985):1278-81
2244211
Lancet. 1999 Oct 9;354(9186):1261-2
10520637
Microbiol Mol Biol Rev. 2000 Sep;64(3):548-72
10974126
J Bacteriol. 1937 Jan;33(1):1-12
16559982
J Clin Microbiol. 2007 Jul;45(7):2105-9
17507510
Science. 2006 Oct 13;314(5797):308-12
16973841
Appl Environ Microbiol. 2008 Aug;74(15):4898-909
18487399
J Clin Immunol. 2004 Nov;24(6):664-73
15622451
Mol Pathol. 2002 Apr;55(2):84-90
11950955
Dig Dis Sci. 2000 Apr;45(4):723-9
10759242
Ann N Y Acad Sci. 2007 Apr;1102:109-20
17470915
Emerg Infect Dis. 2008 Oct;14(10):1665-7
18826844
Virus Res. 2007 Jan;123(1):19-29
16965832
Biotechniques. 2004 Oct;37(4):642-4, 646, 648 passim
15517976
FEBS Lett. 1996 Jan 8;378(2):145-9
8549821
Emerg Infect Dis. 2008 Dec;14(12):1883-6
19046511
Microbiol Mol Biol Rev. 2004 Dec;68(4):669-85
15590779
Genome Biol. 2001;2(6):REVIEWS1017
11423012
Clin Cornerstone. 2003;Suppl 3:S12-20
14992416
Science. 1999 Dec 17;286(5448):2333-7
10600742
J Med Virol. 2007 May;79(5):605-15
17385684
Lancet. 2000 Aug 26;356(9231):772
11085720
N Engl J Med. 1992 Jul 30;327(5):293-301
1377787
J Pediatr. 2001 Mar;138(3):366-72
11241044
Virus Res. 2007 Jun;126(1-2):9-18
17313986
Microbiol Immunol. 1999;43(7):679-89
10529109
J Clin Microbiol. 2005 Nov;43(11):5721-32
16272510
FASEB J. 2009 Apr;23(4):1064-71
19036857
Emerg Infect Dis. 2007 Mar;13(3):396-403
17552092
Science. 1993 Nov 5;262(5135):914-7
8235615
PLoS One. 2008 Apr 02;3(4):e1847
18382652
Cell. 1990 Oct 19;63(2):353-62
2170026
Clin Infect Dis. 2006 Oct 15;43(8):e71-6
16983602
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):732-7
16407106
Emerg Infect Dis. 2007 Jun;13(6):899-901
17553231
Lancet. 2000 May 6;355(9215):1614-5
10821368
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2365-70
19164560
J Clin Microbiol. 2006 Nov;44(11):4157-62
17005760
Microbes Infect. 2006 Jun;8(7):1813-25
16730210
Proc Natl Acad Sci U S A. 2004 May 4;101(18):6888-93
15107500
Emerg Infect Dis. 2008 Nov;14(11):1793-6
18976575
Science. 2009 Jul 10;325(5937):204-6
19590002
J Neuroimmunol. 2006 Apr;173(1-2):126-34
16494951
MMWR Morb Mortal Wkly Rep. 2004 Apr 9;53(13):281-4
15071426
Rev Infect Dis. 1990 Nov-Dec;12(6):1139-46
2267489
J Pediatr. 1978 Oct;93(4):699-703
702254
J Virol Methods. 1997 Jun;66(1):39-50
9220389
Clin Microbiol Rev. 1998 Jul;11(3):480-96
9665979
J Neurovirol. 1999 Oct;5(5):495-9
10568886
J Virol. 2006 Apr;80(7):3135-46
16537582
Cell. 1995 May 5;81(3):323-30
7736585
Arch Microbiol. 1978 May 30;117(2):189-96
678024
J Med Virol. 2006 Sep;78(9):1232-40
16847968
Emerg Infect Dis. 2005 Feb;11(2):310-3
15752453
Annu Rev Microbiol. 1977;31:107-33
334036
J Infect Dis. 1999 Feb;179(2):295-302
9878011
Genome Res. 2004 Mar;14(3):398-405
14993206
J Clin Microbiol. 2004 Apr;42(4):1564-9
15071005
Clin Microbiol Rev. 1996 Jan;9(1):18-33
8665474
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11404-9
15277677
Antiviral Res. 1985 Feb;5(1):39-48
3985607
Lancet. 1977 Mar 12;1(8011):571-3
65662
J Clin Virol. 2007 Jun;39(2):67-75
17482871
Nature. 2008 Jul 24;454(7203):436-44
18650914
J Neurovirol. 1999 Dec;5(6):604-12
10602401
Ann Neurol. 2002 Jun;51(6):673-80
12112071
Mass Spectrom Rev. 2005 Mar-Apr;24(2):265-85
15389854
J Clin Immunol. 2003 Nov;23(6):504-17
15031638
Microbiol Immunol. 1995;39(3):161-8
7603360
Emerg Infect Dis. 2006 Apr;12(4):692-5
16704825
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2927-32
17293459
Science. 1964 May 15;144(3620):862-3
14151624
Clin Infect Dis. 2000 Mar;30(3):413-8
10722421
Nat Med. 2000 Dec;6(12):1375-9
11100123
Mol Psychiatry. 2002;7 Suppl 2:S44-6
12142948
Genome Res. 1996 Oct;6(10):986-94
8908518
Virology. 1995 Jun 20;210(1):1-8
7793061
Arch Gen Psychiatry. 2004 Aug;61(8):774-80
15289276
MMWR Morb Mortal Wkly Rep. 2003 Aug 15;52(32):769-72
12917583
N Engl J Med. 2001 Jun 14;344(24):1807-14
11407341
Emerg Infect Dis. 2007 Jan;13(1):73-81
17370518
PLoS One. 2008 Sep 04;3(9):e3140
18769550
J Clin Microbiol. 2007 Nov;45(11):3655-64
17804649
J Virol. 1995 Dec;69(12):8132-6
7494336
Pediatr Res. 2000 Jan;47(1):64-72
10625084
Proc Natl Acad Sci U S A. 1996 May 28;93(11):5177-84
8643549
Arch Virol. 1997;142(10):2035-42
9413511
Nat Rev Cancer. 2002 May;2(5):342-50
12044010
Vet Pathol. 2000 May;37(3):208-24
10810985
Neurology. 2000 Jan 11;54(1):20-5
10636120
J Allergy Clin Immunol. 2009 Jan;123(1):98-104.e1
19027147
Science. 1970 Jul 10;169(3941):203-4
5427356
J Infect Dis. 2003 Mar 15;187(6):1000-9
12660947
Neurology. 2004 Apr 27;62(8):1372-7
15111676
Cell. 1989 Dec 1;59(5):847-57
2574076
J Gen Virol. 2009 Jun;90(Pt 6):1371-1381
19264616
Nature. 2005 Sep 15;437(7057):356-61
16163346
N Engl J Med. 2008 Mar 6;358(10):991-8
18256387
Lancet. 1999 Oct 9;354(9186):1253-6
10520634
J Clin Microbiol. 2007 Jul;45(7):2340-3
17494722
PLoS One. 2009 Dec 31;4(12):e8540
20046873
J Infect Dis. 1997 Dec;176 Suppl 2:S125-8
9396695
J Virol Methods. 2007 Jan;139(1):78-84
17052763
Yale J Biol Med. 1976 May;49(2):175-95
782050
Nucleic Acids Res. 2006;34(22):6605-11
17135211
J Natl Cancer Inst. 1995 Jun 7;87(11):796-802
7791229
Science. 2005 Jun 10;308(5728):1635-8
15831718
Ann Neurol. 2001 Feb;49(2):249-53
11221802
Virol J. 2008 Jul 31;5:88
18671869
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4250-5
15016918
Science. 2005 Oct 7;310(5745):77-80
16210530
J Infect Dis. 2006 Nov 15;194(10):1398-402
17054069