Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae.

摘要: Streptococcus pneumoniae (the pneumococcus) is an aerotolerant, catalase-deficient streptococcal species that resides predominately on the surface of human airway. This pathogen characterized by impressive degree interstrain diversity, as demonstrated ability different isolates to synthesize 90 currently described types capsular polysaccharide, its immunodominant antigen. In addition this it displays intrastrain variation in expression many factors contribute host-bacterial interaction, including proteins, teichoic acid, and production high levels hydrogen peroxide (35, 46). The pneumococcus phase varies between two phenotypes, distinguished differences colony opacity, allow organism either colonize mucosal nasopharynx or infect bloodstream (23, 45, 47). Recently, information complete genome sequences unrelated strains S. has become available (19, 41). Comparison pneumococcal genomes reveals a difference size 122,222 bp 193 open reading frames with overall level nucleotide sequence similarity <90%. These observations suggest that, species, highly plastic varied diversity may be important capacity adapt host well environments. However, should noted variability tends concentrated limited regions, much several gene clusters encompassing only 160 kb (15). Factors genetic include recombinational events occurring both within strains, frequency distribution insertion make up about 5% genome, presence large numbers unstable duplications (41, 43). Transformation especially relevant, because naturally competent, transformation-mediated horizontal transfer common. role transformation dissemination antibiotic resistance phenotypes pneumococci from other oral streptococci pneumococcus, for instance, been extensively documented (3, 7, 8). Another observation derived whole genomic analysis occurrence incomplete genes fragments, which are unlikely have generated solely homologous events. strain R6, at least 60 >2% orthologous partial truncated (19). finding was unexpected considering pneumoniae's relatively compact 2.04 2.16 Mb completely sequenced It proposed one source might frameshift mutations slipped-strand mispairing iterative DNA motifs referred “microsatellites,” depend mechanism adaptation (31, 41, 42). Eighteen percent TIGR4 isolate were reported contain short-sequence repeats, although few instances did these greater than nine tandem repeats (41). bacterial most previously repetitive vary detectable considerably longer repeating units, there reports short 7 subject slippage (6, 16). There type any gram-positive our knowledge, no prior examples changes length (25). The purpose study characterize instability pneumococcus. Our results demonstrate spontaneous occur involve rearrangements nontandem oxidative damage caused largely endogenous production.