Simple Sequence Repeats and Genome Plasticity in Streptococcus agalactiae

ABSTRACT Simple sequence repeats (SSRs) and their role in phase variation have been extensively studied in Gram-negative organisms, where they have been associated with antigenic variation and other adaptation strategies. In this study, we apply comparative genomics in order to find evidence of slipped-strand mispairing in the human Gram-positive pathogen Streptococcus agalactiae. In two consecutive screenings, 2,233 (650 + 1,583) SSRs were identified in our reference genome 2603V/R, and these loci were examined in seven other S. agalactiae genomes. A total of 56 SSR loci were found to exhibit variation, where gain or loss of repeat units was observed in at least one other genome, resulting in aberrant genotypes. Homopolymeric adenine tracts predominated among the repeats that varied. Positional analysis revealed that long polyadenine tracts were overrepresented in the 5′ ends of open reading frames (ORFs) and underrepresented in the 3′ ends. Repeat clustering in ORFs was also examined, and the highest degree of clustering was observed for a capsule biosynthesis gene and a pilus sortase. A statistical analysis of observed over expected ratios suggested a selective pressure against long homopolymeric tracts. Altered phenotypes were verified for three genes encoding surface-attached proteins, in which frameshifts or fusions led to truncation of proteins and/or affected surface localization through loss or gain of the cell wall sorting signal. The data suggest that SSRs contributes to genome plasticity in S. agalactiae but that the bet-hedging strategy is different from Gram-negative organisms.

[1]  M. Feldman,et al.  Evolution of Stochastic Switching Rates in Asymmetric Fitness Landscapes , 2009, Genetics.

[2]  J. Bryan,et al.  Streptococcus agalactiae CspA Is a Serine Protease That Inactivates Chemokines , 2008, Journal of bacteriology.

[3]  V. Masignani,et al.  BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus survival in human blood , 2007, Molecular microbiology.

[4]  Richard Moxon,et al.  Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. , 2006, Annual review of genetics.

[5]  D. Hendrixson.  A phase‐variable mechanism controlling the Campylobacter jejuni FlgR response regulator influences commensalism , 2006, Molecular microbiology.

[6]  H. Tettelin,et al.  Identification of novel cps locus polymorphisms in nontypable group B Streptococcus. , 2006, Journal of medical microbiology.

[7]  Jaideep P. Sundaram,et al.  Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome". , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. Baker,et al.  Group B streptococcal infections in elderly adults. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  R. Rappuoli,et al.  Genome Analysis Reveals Pili in Group B Streptococcus , 2005, Science.

[10]  H. Tettelin,et al.  Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen , 2005, Science.

[11]  Andrew W. Hammer,et al.  Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression , 2005, Genome Biology.

[12]  M. W. van der Woude,et al.  Phase and Antigenic Variation in Bacteria , 2004, Clinical Microbiology Reviews.

[13]  N. Saunders,et al.  The diversity within an expanded and redefined repertoire of phase-variable genes in Helicobacter pylori. , 2004, Microbiology.

[14]  N. Saunders,et al.  Diversity in coding tandem repeats in related Neisseria spp. , 2003, BMC Microbiology.

[15]  K. M. Puopolo,et al.  Upstream short sequence repeats regulate expression of the alpha C protein of group B Streptococcus , 2003, Molecular microbiology.

[16]  N. Mouchel,et al.  Experimentally revised repertoire of putative contingency loci in Neisseria meningitidis strain MC58: evidence for a novel mechanism of phase variation , 2003, Molecular microbiology.

[17]  B. Eikmanns,et al.  Analysis of RogB-Controlled Virulence Mechanisms and Gene Expression in Streptococcus agalactiae , 2003, Infection and Immunity.

[18]  Buddhaditta Bose,et al.  MICAS: a fully automated web server for microsatellite extraction and analysis from prokaryote and viral genomic sequences. , 2003, Applied bioinformatics.

[19]  D. Shelver,et al.  A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen. , 2003, The Journal of clinical investigation.

[20]  Carmen Buchrieser,et al.  Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease , 2002, Molecular microbiology.

[21]  Ian T. Paulsen,et al.  Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Weiser,et al.  Short-Sequence Tandem and Nontandem DNA Repeats and Endogenous Hydrogen Peroxide Production Contribute to Genetic Instability of Streptococcus pneumoniae , 2002, Journal of bacteriology.

[23]  B. Duim,et al.  Homonucleotide stretches in chromosomal DNA of Campylobacter jejuni display high frequency polymorphism as detected by direct PCR analysis. , 2002, FEMS microbiology letters.

[24]  Lori A. S. Snyder,et al.  Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. , 2001, Microbiology.

[25]  S. Salzberg,et al.  Complete Genome Sequence of a Virulent Isolate of Streptococcus pneumoniae , 2001, Science.

[26]  L. Björck,et al.  Unique regulation of SclB – a novel collagen‐like surface protein of Streptococcus pyogenes , 2001, Molecular microbiology.

[27]  A. Richardson,et al.  Mismatch repair and the regulation of phase variation in Neisseria meningitidis , 2001, Molecular microbiology.

[28]  E. Hansen,et al.  Expression of the Moraxella catarrhalisUspA1 Protein Undergoes Phase Variation and Is Regulated at the Transcriptional Level , 2001, Journal of bacteriology.

[29]  D. Kasper,et al.  Functional Analysis in Type Ia Group B Streptococcusof a Cluster of Genes Involved in Extracellular Polysaccharide Production by Diverse Species of Streptococci* , 2001, The Journal of Biological Chemistry.

[30]  H. Tettelin,et al.  Repeat‐associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58 , 2000, Molecular microbiology.

[31]  S. Salzberg,et al.  Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. , 2000, Science.

[32]  B. Barrell,et al.  The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences , 2000, Nature.

[33]  D. Field,et al.  The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases , 2000, Molecular microbiology.

[34]  M. Gottschalk,et al.  Immunomagnetic Isolation of Streptococcus suis Serotypes 2 and 1/2 from Swine Tonsils , 1999, Journal of Clinical Microbiology.

[35]  Benjamin L. King,et al.  Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori , 1999, Nature.

[36]  A. Schuchat.  Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms , 1998, Clinical Microbiology Reviews.

[37]  Alex van Belkum,et al.  Short-Sequence DNA Repeats in Prokaryotic Genomes , 1998, Microbiology and Molecular Biology Reviews.

[38]  J. Peden,et al.  Simple sequence repeats in the Helicobacter pylori genome , 1998, Molecular microbiology.

[39]  Mark Borodovsky,et al.  The complete genome sequence of the gastric pathogen Helicobacter pylori , 1997, Nature.

[40]  R. Fleischmann,et al.  DNA repeats identify novel virulence genes in Haemophilus influenzae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[41]  P. Cleary,et al.  C5a peptidase alters clearance and trafficking of group A streptococci by infected mice , 1996, Infection and immunity.

[42]  F. Mooi,et al.  Phase variation of H. influenzae fimbriae: Transcriptional control of two divergent genes through a variable combined promoter region , 1993, Cell.

[43]  A. Podbielski,et al.  Similarity between the group B and A streptococcal C5a peptidase genes , 1992, Infection and immunity.

[44]  Vincent A. Fischetti,et al.  Sorting of protein a to the staphylococcal cell wall , 1992, Cell.

[45]  G. Gutman,et al.  Slipped-strand mispairing: a major mechanism for DNA sequence evolution. , 1987, Molecular biology and evolution.

[46]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.