Autoinducer-2 and QseC control biofilm formation and in vivo virulence of Aggregatibacter actinomycetemcomitans.
Biofilm formation by the periodontal pathogen Aggregatibacter actinomycetemcomitans is dependent upon autoinducer-2 (AI-2)-mediated quorum sensing. However, the components that link the detection of the AI-2 signal to downstream gene expression have not been determined. One potential regulator is the QseBC two-component system, which is part of the AI-2-dependent response pathway that controls biofilm formation in Escherichia coli. Here we show that the expression of QseBC in A. actinomycetemcomitans is induced by AI-2 and that induction requires the AI-2 receptors, LsrB and/or RbsB. Additionally, inactivation of qseC resulted in reduced biofilm growth. Since the ability to grow in biofilms is essential for A. actinomycetemcomitans virulence, strains that were deficient in QseC or the AI-2 receptors were examined in an in vivo mouse model of periodontitis. The DeltaqseC mutant induced significantly less alveolar bone resorption than the wild-type strain (P < 0.02). Bone loss in animals infected with the DeltaqseC strain was similar to that in sham-infected animals. The DeltalsrB, DeltarbsB, and DeltalsrB DeltarbsB strains also induced significantly less alveolar bone resorption than the wild type (P < 0.03, P < 0.02, and P < 0.01, respectively). However, bone loss induced by a DeltaluxS strain was indistinguishable from that induced by the wild type, suggesting that AI-2 produced by indigenous microflora in the murine oral cavity may complement the DeltaluxS mutation. Together, these results suggest that the QseBC two-component system is part of the AI-2 regulon and may link the detection of AI-2 to the regulation of downstream cellular processes that are involved in biofilm formation and virulence of A. actinomycetemcomitans.
Novak
Elizabeth A
EA
Research Group in Oral Health and Systemic Disease, University of Louisville School of Dentistry, Room 209, Louisville, Kentucky 40292, USA.
Shao
HanJuan
H
Daep
Carlo Amorin
CA
Demuth
Donald R
DR
D000189:Actinobacillus Infections / Q000382:microbiology*; D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D003773:Dental Plaque / Q000382:microbiology; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005798:Genes, Bacterial / Q000235:genetics; D006714:Homoserine / Q000031:analogs & derivatives* / Q000502:physiology; D007783:Lactones; D051379:Mice; D010518:Periodontitis / Q000382:microbiology; D053038:Quorum Sensing / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine
J Biol Chem. 2009 Oct 16;284(42):28746-53
19690171
FEMS Microbiol Rev. 2001 Aug;25(4):365-404
11524130
Arch Oral Biol. 1994 Dec;39(12):1035-40
7717884
Infect Immun. 1994 Feb;62(2):501-8
8300209
J Immunol. 2007 Aug 15;179(4):2349-58
17675496
Am J Med Sci. 1973 Nov;266(5):387-92
4762345
PLoS Pathog. 2009 Dec;5(12):e1000706
20041169
N Engl J Med. 1966 Jul 28;275(4):181-8
5938866
Mol Microbiol. 2001 Nov;42(3):777-93
11722742
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8951-6
12847292
Mol Microbiol. 1993 Aug;9(4):773-86
8231809
Infect Immun. 2009 Aug;77(8):3294-301
19506009
Mol Microbiol. 2006 Oct;62(2):397-411
17020579
Microbiol Mol Biol Rev. 2007 Dec;71(4):653-70
18063722
Mol Microbiol. 2001 Jul;41(2):463-76
11489131
Microbiology (Reading). 2000 Oct;146 ( Pt 10):2395-2407
11021916
Annu Rev Microbiol. 1996;50:513-52
8905090
J Med Microbiol. 2003 Jul;52(Pt 7):541-545
12808073
Annu Rev Microbiol. 1997;51:527-64
9343359
J Bacteriol. 2006 Jan;188(1):305-16
16352847
PLoS Pathog. 2009 Aug;5(8):e1000553
19696934
Mol Microbiol. 2006 Jun;60(6):1446-56
16796680
J Bacteriol. 2007 Aug;189(15):5559-65
17526716
Mol Microbiol. 2003 Nov;50(4):1411-27
14622426
Infect Immun. 2006 Jul;74(7):4021-9
16790775
J Clin Microbiol. 2005 Nov;43(11):5721-32
16272510
Infect Immun. 1980 Sep;29(3):1013-20
6968718
J Periodontol. 1992 Apr;63(4 Suppl):322-31
1573546
J Bacteriol. 2007 Aug;189(16):6011-20
17557827
Curr Opin Microbiol. 1999 Dec;2(6):582-7
10607620
Infect Immun. 2003 Jan;71(1):298-308
12496179
Mol Microbiol. 2002 Feb;43(3):809-21
11929534
Adv Dent Res. 2003 Dec;17:95-9
15126217
J Bacteriol. 2001 Jul;183(13):3903-9
11395453
Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5889-94
19289831
Periodontol 2000. 2006;42:80-7
16930307
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11229-34
10500159
Infect Immun. 2007 Sep;75(9):4211-8
17591788
Bioorg Med Chem Lett. 2003 Nov 17;13(22):3897-900
14592470
Curr Opin Microbiol. 2003 Apr;6(2):191-7
12732311
J Bacteriol. 2003 Jan;185(1):274-84
12486064
BMC Oral Health. 2006 Jun 15;6 Suppl 1:S14
16934115
Microbiol Mol Biol Rev. 1998 Dec;62(4):1244-63
9841671
Microbiology (Reading). 2003 Feb;149(Pt 2):279-294
12624191
Infect Immun. 2006 Jul;74(7):3834-44
16790755
Microbiology (Reading). 2008 Feb;154(Pt 2):528-538
18227257
J Bacteriol. 2002 Feb;184(4):873-83
11807045
Biometals. 2007 Jun;20(3-4):365-77
17206384
J Med Microbiol. 2007 Jan;56(Pt 1):119-128
17172526
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8789-93
10922036
Infect Immun. 2001 Dec;69(12):7625-34
11705942
Infect Immun. 1983 Apr;40(1):205-12
6572616
J Bacteriol. 1993 Jun;175(11):3247-52
8501028
Adv Dent Res. 1997 Apr;11(1):176-85
9524454
Trends Cell Biol. 2004 Nov;14(11):648-56
15519854