Borrelia burgdorferi sigma54 is required for mammalian infection and vector transmission but not for tick colonization.
Previous studies have shown that a sigma54-sigma(S) cascade regulates the expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme disease. Here, we demonstrate that these sigma factors, both together and independently, regulate a much more extensive number of genes and cellular processes. Microarray analyses of sigma54 and sigma(S) mutant strains identified 305 genes regulated by sigma54 and 145 regulated by sigma(S), whereas the sigma54-sigma(S) regulatory cascade appears to control 48 genes in B. burgdorferi. In silico analyses revealed that nearly 80% of genes with altered expression in the sigma54 mutant were linked to potential sigma54-dependent promoters. Many sigma54-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma54 was required by B. burgdorferi to infect mammals. Surprisingly, sigma54 mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma54-sigma(S) regulatory network was not involved in long-term survival in ticks. However, sigma54 mutants did not enter the salivary glands during tick feeding, indicating that sigma54-regulated genes were involved in the transmission process.
Fisher
Mark A
MA
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
Grimm
Dorothee
D
Henion
Amy K
AK
Elias
Abdallah F
AF
Stewart
Philip E
PE
Rosa
Patricia A
PA
Gherardini
Frank C
FC
D000818:Animals; D001096:Arachnid Vectors / Q000382:microbiology*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D018884:Ixodes / Q000382:microbiology*; D008193:Lyme Disease / Q000209:etiology / Q000635:transmission; D051379:Mice; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D051877:RNA Polymerase Sigma 54; D018085:Regulon; D012469:Salivary Glands / Q000382:microbiology; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D012808:Sigma Factor; D012321:DNA-Directed RNA Polymerases; D051877:RNA Polymerase Sigma 54
Microbiol Rev. 1989 Sep;53(3):367-76
2677638
Infect Immun. 2004 Nov;72(11):6433-45
15501774
J Clin Microbiol. 1991 Feb;29(2):236-43
2007630
J Clin Invest. 1991 Jul;88(1):82-92
2056133
Mol Microbiol. 1991 Dec;5(12):2875-82
1809831
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11978-82
1465428
Genome Res. 1996 Oct;6(10):986-94
8908518
Nature. 1997 Dec 11;390(6660):580-6
9403685
Infect Immun. 1998 Jun;66(6):2674-83
9596733
Infect Immun. 1998 Aug;66(8):3689-97
9673250
Mol Microbiol. 1998 Nov;30(4):711-23
10094620
Curr Opin Microbiol. 1999 Apr;2(2):148-52
10322169
Infect Immun. 1989 Nov;57(11):3276-80
2680969
Nucleic Acids Res. 1999 Nov 15;27(22):4305-13
10536136
J Clin Microbiol. 2000 Jan;38(1):382-8
10618120
Mol Microbiol. 2000 Feb;35(3):490-516
10672174
Infect Immun. 2000 Mar;68(3):1222-30
10678930
J Bacteriol. 2000 May;182(9):2445-52
10762244
Mol Microbiol. 2000 Apr;36(2):341-51
10792721
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12724-9
11675503
J Bacteriol. 2001 Dec;183(24):7126-34
11717271
Infect Immun. 2002 Feb;70(2):491-7
11796574
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1562-7
11830671
Infect Immun. 2002 Apr;70(4):2139-50
11895980
J Bacteriol. 2002 Jun;184(11):3122-5
12003955
J Exp Med. 2002 Jul 15;196(2):275-80
12119353
J Bacteriol. 2002 Sep;184(17):4881-90
12169614
Infect Immun. 2002 Sep;70(9):4851-8
12183529
Infect Immun. 2003 Apr;71(4):1689-705
12654782
Infect Immun. 2003 Jun;71(6):3371-83
12761121
J Med Entomol. 2003 May;40(3):364-70
12943118
J Microsc. 2003 Nov;212(Pt 2):107-21
14629560
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15953-8
14671329
J Clin Invest. 2004 Jan;113(2):220-30
14722614
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3142-7
14970347
Mol Microbiol. 2004 Apr;52(1):25-38
15049808
Appl Environ Microbiol. 2004 Apr;70(4):2520-4
15066853
Microbiology. 2004 May;150(Pt 5):1581-90
15133119
Vector Borne Zoonotic Dis. 2004 Summer;4(2):159-68
15228817
Infect Immun. 2004 Sep;72(9):5419-32
15322040
Infect Immun. 2004 Oct;72(10):5938-46
15385497