title: Characterization of sil in invasive group A and G streptococci: antibodies against bacterial pheromone peptide SilCR result in severe infection.
abstract: Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS. sil encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that sil is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained sil expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the sil locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.
authors: Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Ayelet
authors: A
authors: Michael-Gayego
authors: Mary
authors: M
authors: Dan-Goor
authors: Joseph
authors: J
authors: Jaffe
authors: Carlos
authors: C
authors: Hidalgo-Grass
authors: Allon E
authors: AE
authors: Moses
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010675:Pheromones / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053038:Quorum Sensing; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013291:Streptococcus / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D000907:Antibodies, Bacterial; D010455:Peptides; D010675:Pheromones; D037521:Virulence Factors
references: Emerg Infect Dis. 2002 Apr;8(4):421-6
references: 11971778
references: J Exp Med. 1935 Feb 28;61(3):335-49
references: 19870362
references: Infect Immun. 1991 Jul;59(7):2305-10
references: 2050400
references: Lancet. 2004 Feb 28;363(9410):696-703
references: 15001327
references: Mol Microbiol. 2007 Feb;63(4):1209-22
references: 17238919
references: FEMS Microbiol Lett. 2003 Dec 12;229(2):259-64
references: 14680708
references: Infect Immun. 1987 Mar;55(3):502-6
references: 3546129
references: J Clin Invest. 2003 Nov;112(9):1291-9
references: 14597753
references: PLoS Pathog. 2009 Nov;5(11):e1000651
references: 19893632
references: Infect Immun. 1987 Mar;55(3):753-7
references: 3102380
references: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11140-4
references: 7479953
references: Microb Pathog. 1987 Nov;3(5):339-50
references: 3332910
references: J Clin Microbiol. 2007 Jun;45(6):2002-4
references: 17376880
references: Infect Immun. 2001 Aug;69(8):4858-69
references: 11447161
references: J Bacteriol. 2011 Dec;193(23):6651-63
references: 21949075
references: Medicine (Baltimore). 1985 Mar;64(2):75-88
references: 3974442
references: FEMS Immunol Med Microbiol. 2002 Oct 11;34(2):159-67
references: 12381468
references: Mol Microbiol. 2002 Oct;46(1):87-99
references: 12366833
references: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7059-64
references: 16636287
references: Emerg Infect Dis. 2004 Aug;10(8):1455-60
references: 15496248
references: Proc Natl Acad Sci U S A. 1989 Apr;86(8):2757-60
references: 2704745
references: J Clin Microbiol. 2003 Oct;41(10):4655-9
references: 14532198
references: J Mol Biol. 1975 Nov 5;98(3):503-17
references: 1195397
references: Lancet. 2002 Jan 12;359(9301):124-9
references: 11809255
references: Int J Antimicrob Agents. 2006 Oct;28(4):313-9
references: 16973336
references: Methods Enzymol. 1991;204:556-86
references: 1658571
references: Mol Microbiol. 1997 Jun;24(5):895-904
references: 9219998
references: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4668-73
references: 11917108
references: FEMS Microbiol Lett. 2003 Feb 28;219(2):291-5
references: 12620634