Mosaic Genes and Mosaic Chromosomes: Intra- and Interspecies Genomic Variation of
            <i>Streptococcus pneumoniae</i>

Hakenbeck, Regine; Balmelle, Nadège; Weber, Beate; Gardès, Christophe; Keck, Wolfgang; Saizieu, Antoine de

doi:10.1128/iai.69.4.2477-2486.2001

Cited by 194 publications

(144 citation statements)

References 45 publications

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“…The extremely high nucleotide variability, resulting in a mosaic structure of the zmp genes, hinders epidemiological approaches using nucleotide probes or primers directed to the coding sequences (Hakenbeck et al, 2001). We therefore decided to trace the zmp genes by employing primers for conserved sequences outside the genes.…”

Section: Discussionmentioning

confidence: 99%

Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae: association of the full array with a clonal cluster comprising serotypes 8 and 11A

et al. 2006

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Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae: association of the full array with a clonal cluster comprising serotypes 8 and 11A Pneumococci display large zinc metalloproteinases on the surface, including the IgA protease, which cleaves human IgA1 in the hinge region, the ZmpC proteinase, which cleaves human matrix metalloproteinase 9 (MMP-9), and two other proteinases, ZmpB and ZmpD, whose substrates have not yet been identified. Surface metalloproteinases are antigenic and have been linked to virulence. The genes encoding these proteinases reside in three distinct loci: two loci specific for zmpB and zmpC, and a third, the iga locus, containing iga and zmpD. Data obtained by this and other groups have shown that pneumococcal metalloproteinase genes are transcribed and yield mature and enzymatically active proteins. Since the presence of the four proteinase genes is variable in the pneumococcal strains whose genomes have been sequenced, the presence of these genes in a collection of 218 pneumococcal isolates, mostly from invasive disease, was investigated. The data showed that zmpB and iga were present in all the isolates examined, while zmpC and zmpD were present in a variable proportion of the isolates (in 18 and 49 %, respectively). Interestingly, isolates carrying both zmpC and zmpD were found to belong mainly to two serotypes (sts), 8 and 11A. By molecular typing, st 8 and st 11A isolates appeared to belong to the same clonal cluster. The presence of these two additional metalloproteinases could contribute to the fitness of particular pneumococcal clones. INTRODUCTIONStreptococcus pneumoniae (pneumococcus) is a common and important human pathogen. Pneumococci are the chief cause of community-acquired pneumonia and bacterial meningitis, the second-most-prevalent cause of sepsis, and one of the main causes of otitis media (Gillespie, 1989). The main virulence factors of S. pneumoniae are the capsule, the pneumolysin that is a cholesterol-dependent cytolysin, and some pneumococcal surface proteins and enzymes, including PspA, PspC, neuraminidase and hyaluronidase (Paton et al., 1993;Mitchell, 2000;Chapuy-Regaud et al., 2003;Iannelli et al., 2004). A characteristic feature of S. pneumoniae is the presence of large zinc metalloproteinases on the cell surface. These enzymes have a common structure (Pfam Accession no. PF02395) and are present not only in S. pneumoniae but also in related oral streptococci, such as Streptococcus sanguis, Streptococcus gordonii, Streptococcus mitis and Streptococcus oralis .From the published genome sequences, it can be inferred that S. pneumoniae possesses two (strain R6, rough derivative of serotype 2; Hoskins et al., 2001), three (strain TIGR4, serotype 4; Tettelin et al., 2001) or even four (strain G54, serotype 19F;Dopazo et al., 2001) zinc metalloproteinase genes, depending on the strain. All the above-mentioned strains possess iga and zmpB, encoding the IgA protease and ZmpB, respectively. In addition, strains TIGR4 and G54 possess the metal...

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Section: Discussionmentioning

confidence: 99%

Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae: association of the full array with a clonal cluster comprising serotypes 8 and 11A

et al. 2006

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“…Homologous sequences flanking the polymorphic region on either side (i.e., dexB or aliA sequences for the cap locus) (25) can provide a homologous recombination anchor and favor the formation of InsDels in the flanking heterologous cap region. Evidence has been obtained that two S. pneumoniae isolates can differ by up to 10% of the chromosome (26). Therefore this scenario can lead to shuffling of DNA sequences at several places in the S. pneumoniae chromosome.…”

Section: A D-loop Resolvase In Transformation?mentioning

confidence: 99%

Homologous recombination at the border: Insertion-deletions and the trapping of foreign DNA in Streptococcus pneumoniae

Prudhomme

Libante

Claverys

2002

Proc. Natl. Acad. Sci. U.S.A.

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Integration of foreign DNA was observed in the Gram-positive human pathogen Streptococcus pneumoniae (pneumococcus) after transformation with DNA from a recombinant Escherichia coli bacteriophage carrying a pneumococcal insert. Segments of DNA replaced chromosomal sequences adjacent to the region homologous with the pneumococcal insert, whence the name insertion-deletion. Here we report that a pneumococcal insert was absolutely required for insertion-deletion formation, but could be as short as 153 bp; that the sizes of foreign DNA insertions (289 -2,474 bp) and concomitant chromosomal deletions (45-1,485 bp) were not obviously correlated; that novel joints clustered preferentially within segments of high GC content; and that the crossovers in 29 independent novel joints were located 1 bp from the border or within short (3-10 nt long) stretches of identity (microhomology) between resident and foreign DNA. The data are consistent with a model in which the insert serving as a homologous recombination anchor favors interaction and subsequent illegitimate recombination events at microhomologies between foreign and resident sequences. The potential of homologydirected illegitimate recombination for genome evolution was illustrated by the trapping of functional heterologous genes. G enetic transformation, which was discovered in the Grampositive Streptococcus pneumoniae (pneumococcus) (1), is believed to play a central role in the biology of this human pathogen through its contribution to genetic plasticity (see ref.2 for a review). Transformation with naked DNA allows intraspecies and interspecies gene transfer. As such exchanges involve homologous recombination, they are generally ''conservative,'' i.e., they do not result in the creation of novel sequences but simply in a redistribution of previously existing genes. However, a pre-existing gene also can be modified when the two interacting sequences are partly divergent. Homologous recombination then leads to the production of mosaic genes, as exemplified in the case of the pbp genes of S. pneumoniae that encode altered penicillin-binding proteins with decreased affinity for ␤-lactam antibiotics (see ref. 3 for a review).Besides these conservative facets of transformation, is there any potential for the creation of novel sequence combinations or genes? The observation that transformation with chimeric donor DNA is mutagenic (4) suggested that shuffling and reassembly of previously unrelated sequences could readily occur in S. pneumoniae. The chimeric DNA extracted from a recombinant Escherichia coli bacteriophage carrying a pneumococcal insert produced illegitimate recombinants at a frequency of about 0.5% that of homologous recombinants (4). Illegitimate recombinants resulted from simultaneous insertion of heterologous vector (i.e., ) sequences and deletion of chromosomal sequences adjacent to the region homologous to the insert. These illegitimate events were therefore termed insertion-deletions (InsDels). As the pneumococcal insert in the chimeric donor seemed r...

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“…As is the case with many genes in pneumococci (44,45), the murMN genes, like PBP2x, exhibit a mosaic structure which may explain the strain-dependent differences in branched muropeptide content. The variability of the murMN genes appears to be responsible for variations in the catalytic efficiencies of their products (30,95).…”

Section: Biosynthesis Of Branched Cell Wall Peptides and Impact On ␤-mentioning

confidence: 99%

FemABX Peptidyl Transferases: a Link between Branched-Chain Cell Wall Peptide Formation and β-Lactam Resistance in Gram-Positive Cocci

Rohrer

Berger‐Bächi

2003

Antimicrob Agents Chemother

108

102

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Mosaic Genes and Mosaic Chromosomes: Intra- and Interspecies Genomic Variation of Streptococcus pneumoniae

Cited by 194 publications

References 45 publications

Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae: association of the full array with a clonal cluster comprising serotypes 8 and 11A

Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae: association of the full array with a clonal cluster comprising serotypes 8 and 11A

Homologous recombination at the border: Insertion-deletions and the trapping of foreign DNA in Streptococcus pneumoniae

FemABX Peptidyl Transferases: a Link between Branched-Chain Cell Wall Peptide Formation and β-Lactam Resistance in Gram-Positive Cocci

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