Structure, Regulation, and Putative Function of the Arginine Deiminase System of Streptococcus suis

ABSTRACT Streptococcus suis is an important cause of infectious diseases in young pigs. Little is known about the virulence factors or protective antigens of S. suis. Recently, we have identified two proteins of the arginine deiminase system (ADS) of S. suis, which were temperature induced and expressed on the streptococcal surface (N. Winterhoff, R. Goethe, P. Gruening, M. Rohde, H. Kalisz, H. E. Smith, and P. Valentin-Weigand, J. Bacteriol. 184:6768-6776, 2002). In the present study, we analyzed the complete ADS of S. suis. Due to their homologies to the recently published S. gordonii ADS genes, the genes for arginine deiminase, ornithine carbamoyl-transferase, and carbamate kinase, which were previously designated adiS, octS, and ckS, respectively, were renamed arcA, arcB, and arcC, respectively. Our data revealed that arcA, arcB, and arcC of the S. suis ADS are transcribed from an operon (arcABC operon). Additionally, putative ADS-associated genes were cloned and sequenced which, however, did not belong to the arcABC operon. These were the flpS gene upstream of the arcABC operon with homology to the flp transcription regulator of S. gordonii and the arcD, arcT, arcH, and argR genes downstream of the arcABC operon with high homologies to a putative arginine-ornithine antiporter, a putative dipeptidase of S. gordonii, a putative β-N-acetylhexosaminidase of S. pneumoniae, and a putative arginine repressor of S. gordonii, respectively. The transcriptional start point of the arcABC operon was determined, and promoter analysis provided evidence that multiple factors contribute to the regulation of the ADS. Thus, a putative binding site for a transcription regulator of the Crp/Fnr family, an ArgR-binding site, and two cis-acting catabolite response elements were identified in the promoter-operator region of the operon. Consistent with this, we could demonstrate that the ADS of S. suis is inducible by arginine and reduced O2 tension and subject to carbon catabolite repression. Furthermore, comparing an arcA knockout mutant in which expression of the three operon-encoded proteins was abolished with the parental wild-type strain showed that the arcABC operon of S. suis contributes to survival under acidic conditions.

[1]  M. Rohde,et al.  Non‐encapsulated strains reveal novel insights in invasion and survival of Streptococcus suis in epithelial cells , 2004, Cellular microbiology.

[2]  R. Burne,et al.  Control of Expression of the Arginine Deiminase Operon of Streptococcus gordonii by CcpA and Flp , 2004, Journal of bacteriology.

[3]  R. Burne,et al.  Characterization of the Arginine Deiminase Operon of Streptococcus rattus FA-1 , 2004, Applied and Environmental Microbiology.

[4]  W. Hillen,et al.  Global control of sugar metabolism: a Gram-positive solution , 2004, Antonie van Leeuwenhoek.

[5]  Heidi J Sofia,et al.  Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. , 2003, FEMS microbiology reviews.

[6]  E. Ziomek,et al.  Influence of group A streptococcal acid glycoprotein on expression of major virulence factors and internalization by epithelial cells. , 2003, Microbial pathogenesis.

[7]  W. Griffiths,et al.  Identification of immunoreactive proteins during acute human giardiasis. , 2003, The Journal of infectious diseases.

[8]  M. Rohde,et al.  Identification and Characterization of Two Temperature-Induced Surface-Associated Proteins of Streptococcus suis with High Homologies to Members of the Arginine Deiminase System of Streptococcus pyogenes , 2002, Journal of bacteriology.

[9]  F. González-Candelas,et al.  Evolution of arginine deiminase (ADI) pathway genes. , 2002, Molecular phylogenetics and evolution.

[10]  G. Pérez-Martínez,et al.  The Product of arcR, the Sixth Gene of the arc Operon of Lactobacillus sakei, Is Essential for Expression of the Arginine Deiminase Pathway , 2002, Applied and Environmental Microbiology.

[11]  V. Rubio,et al.  Gene Structure, Organization, Expression, and Potential Regulatory Mechanisms of Arginine Catabolism in Enterococcus faecalis , 2002, Journal of bacteriology.

[12]  R. Burne,et al.  Isolation and Molecular Analysis of the Gene Cluster for the Arginine Deiminase System from Streptococcus gordonii DL1 , 2002, Applied and Environmental Microbiology.

[13]  Link,et al.  UvA-DARE ( Digital Academic Repository ) Identification of virulence factors of Streptococcus suis , 2011 .

[14]  R. Burne,et al.  Isolation and Molecular Analysis of the Gene Cluster for the Arginine Deiminase System from Streptococcus gordonii DL 1 , 2002 .

[15]  P. Reddy,et al.  Cloning and Characterization of the Gene Encoding the Glutamate Dehydrogenase of Streptococcus suis Serotype 2 , 2001, Clinical Diagnostic Laboratory Immunology.

[16]  P. Valentin-Weigand,et al.  Relatedness of Streptococcus suisIsolates of Various Serotypes and Clinical Backgrounds as Evaluated by Macrorestriction Analysis and Expression of Potential Virulence Traits , 2001, Journal of Clinical Microbiology.

[17]  V. Stalon,et al.  Regulation of anaerobic arginine catabolism in Bacillus licheniformis by a protein of the Crp/Fnr family. , 2000, FEMS microbiology letters.

[18]  M. Gottschalk,et al.  The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions. , 2000, Veterinary microbiology.

[19]  G. Dougan,et al.  Characterization of an Isogenic Mutant ofStreptococcus pyogenes Manfredo Lacking the Ability To Make Streptococcal Acid Glycoprotein , 2000, Infection and Immunity.

[20]  Jeffrey Green,et al.  Characterization of the Lactococcus lactis transcription factor FlpA and demonstration of an in vitro switch , 2000, Molecular microbiology.

[21]  A. Sonenshein,et al.  CcpC, a novel regulator of the LysR family required for glucose repression of the citB gene in Bacillus subtilis. , 2000, Journal of molecular biology.

[22]  S. Ehrlich,et al.  Relationships between arginine degradation, pH and survival in Lactobacillus sakei. , 1999, FEMS microbiology letters.

[23]  R. Ebright,et al.  Transcription activation by catabolite activator protein (CAP). , 1999, Journal of molecular biology.

[24]  M. Hecker,et al.  Regulation of the lic Operon ofBacillus subtilis and Characterization of Potential Phosphorylation Sites of the LicR Regulator Protein by Site-Directed Mutagenesis , 1999, Journal of bacteriology.

[25]  V. Monedero,et al.  Elements Involved in Catabolite Repression and Substrate Induction of the Lactose Operon in Lactobacillus casei , 1999, Journal of bacteriology.

[26]  R. Burne,et al.  Regulation of Expression of the Fructan Hydrolase Gene of Streptococcus mutans GS-5 by Induction and Carbon Catabolite Repression , 1999, Journal of bacteriology.

[27]  D. Haas,et al.  The ArgR Regulatory Protein, a Helper to the Anaerobic Regulator ANR during Transcriptional Activation of thearcD Promoter in Pseudomonas aeruginosa , 1999, Journal of bacteriology.

[28]  M. Smits,et al.  Identification and Characterization of thecps Locus of Streptococcus suis Serotype 2: the Capsule Protects against Phagocytosis and Is an Important Virulence Factor , 1999, Infection and Immunity.

[29]  V. Stalon,et al.  The arcABDC Gene Cluster, Encoding the Arginine Deiminase Pathway of Bacillus licheniformis, and Its Activation by the Arginine Repressor ArgR , 1998, Journal of bacteriology.

[30]  J. Goodacre,et al.  Inhibition of Human Peripheral Blood Mononuclear Cell Proliferation by Streptococcus pyogenes Cell Extract Is Associated with Arginine Deiminase Activity , 1998, Infection and Immunity.

[31]  M. Gasson,et al.  A novel regulatory switch mediated by the FNR-like protein of Lactobacillus casei. , 1998, Microbiology.

[32]  M. Nishio,et al.  Characterization of a streptococcal antitumor glycoprotein (SAGP). , 1998, Life sciences.

[33]  J. Harel,et al.  Streptococcus suis serotype 2 mutants deficient in capsular expression. , 1998, Microbiology.

[34]  I. Paulsen,et al.  CcpB, a Novel Transcription Factor Implicated in Catabolite Repression in Bacillus subtilis , 1998, Journal of bacteriology.

[35]  J. Michiels,et al.  The arginine deiminase pathway in Rhizobium etli: DNA sequence analysis and functional study of the arcABC genes , 1997, Journal of bacteriology.

[36]  S. Haataja,et al.  The galactosyl-(alpha 1-4)-galactose-binding adhesin of Streptococcus suis: occurrence in strains of different hemagglutination activities and induction of opsonic antibodies , 1996, Infection and immunity.

[37]  A. Ruepp,et al.  Fermentative arginine degradation in Halobacterium salinarium (formerly Halobacterium halobium): genes, gene products, and transcripts of the arcRACB gene cluster , 1996, Journal of bacteriology.

[38]  T. Henkin.  The role of CcpA transcriptional regulator in carbon metabolism in Bacillus subtilis. , 1996, FEMS microbiology letters.

[39]  G. Rapoport,et al.  Two different mechanisms mediate catabolite repression of the Bacillus subtilis levanase operon , 1995, Journal of bacteriology.

[40]  W. Hillen,et al.  Catabolite repression in Bacillus subtilis: a global regulatory mechanism for the Gram‐positive bacteria? , 1995, Molecular microbiology.

[41]  M. Smits,et al.  High-efficiency transformation and gene inactivation in Streptococcus suis type 2. , 1995, Microbiology.

[42]  M. Gottschalk,et al.  Characterization of Streptococcus suis capsular type 2 haemolysin. , 1995, Microbiology.

[43]  W. Maas,et al.  The arginine repressor of Escherichia coli. , 1994, Microbiological reviews.

[44]  Anton Berg,et al.  Identification, purification, and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis , 1994, Infection and immunity.

[45]  N. Chanter,et al.  Meningitis in pigs caused by Streptococcus suis--a speculative review. , 1993, Veterinary microbiology.

[46]  H. Wisselink,et al.  Identification of two proteins associated with virulence of Streptococcus suis type 2 , 1991, Infection and immunity.

[47]  D. Haas,et al.  Anaerobic regulation of transcription initiation in the arcDABC operon of Pseudomonas aeruginosa , 1991, Journal of bacteriology.

[48]  S. Cole,et al.  Molecular genetic analysis of FNR‐dependent promoters , 1989, Molecular microbiology.

[49]  A. Casiano-Colón,et al.  Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance , 1988, Applied and environmental microbiology.

[50]  H. Zanen,et al.  Meningitis caused by Streptococcus suis in humans. , 1988, Reviews of infectious diseases.

[51]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[52]  G. Bender,et al.  Arginine deiminase system and bacterial adaptation to acid environments , 1987, Applied and environmental microbiology.

[53]  N. Glansdorff,et al.  Biosynthesis and Metabolism of Arginine in Bacteria , 1986, Microbiological reviews.

[54]  J. Marsh,et al.  The pIC plasmid and phage vectors with versatile cloning sites for recombinant selection by insertional inactivation. , 1984, Gene.

[55]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[56]  T. J. Alexander,et al.  The carrier site and carrier rate of Streptococcus suis type II in pigs , 1980, Veterinary Record.

[57]  A. Leeuwenhoek.  The FNR family of transcriptional regulators , 2022 .