BackgroundStreptococcus mutans is the major pathogen of dental caries, and it occasionally causes infective endocarditis. While the pathogenicity of this species is distinct from other human pathogenic streptococci, the species-specific evolution of the genus Streptococcus and its genomic diversity are poorly understood.ResultsWe have sequenced the complete genome of S. mutans serotype c strain NN2025, and compared it with the genome of UA159. The NN2025 genome is composed of 2,013,587 bp, and the two strains show highly conserved core-genome. However, comparison of the two S. mutans strains showed a large genomic inversion across the replication axis producing an X-shaped symmetrical DNA dot plot. This phenomenon was also observed between other streptococcal species, indicating that streptococcal genetic rearrangements across the replication axis play an important role in Streptococcus genetic shuffling. We further confirmed the genomic diversity among 95 clinical isolates using long-PCR analysis. Genomic diversity in S. mutans appears to occur frequently between insertion sequence (IS) elements and transposons, and these diversity regions consist of restriction/modification systems, antimicrobial peptide synthesis systems, and transporters. S. mutans may preferentially reject the phage infection by clustered regularly interspaced short palindromic repeats (CRISPRs). In particular, the CRISPR-2 region, which is highly divergent between strains, in NN2025 has long repeated spacer sequences corresponding to the streptococcal phage genome.ConclusionThese observations suggest that S. mutans strains evolve through chromosomal shuffling and that phage infection is not needed for gene acquisition. In contrast, S. pyogenes tolerates phage infection for acquisition of virulence determinants for niche adaptation.

Streptococcus pyogenes (group A streptococcus (GAS)) is a pathogen that invades non-phagocytic host cells, and causes a variety of acute infections such as pharyngitis. Our group previously reported that intracellular GAS is effectively degraded by the host-cell autophagic machinery, and that a cholesterol-dependent cytolysin, streptolysin O (SLO), is associated with bacterial escape from endosomes in epithelial cells. However, the details of both the intracellular behavior of GAS and the process leading to its autophagic degradation remain unknown. In this study, we found that two host small G proteins, Rab5 and Rab7, were associated with the pathway of autophagosome formation and the fate of intracellular GAS. Rab5 was involved in bacterial invasion and endosome fusion. Rab7 was clearly multifunctional, with roles in bacterial invasion, endosome maturation, and autophagosome formation. In addition, this study showed that the bacterial cytolysin SLO supported the escape of GAS into the cytoplasm from endosomes, and surprisingly, a SLOdeficient mutant of GAS was viable longer than the wild-type strain although it failed to escape the endosomes. This intracellular behavior of GAS is unique and distinct from that of other types of bacterial invaders. Our results provide a new picture of GAS infection and host-cell responses in epithelial cells. Streptococcus pyogenes (group A streptococcus; GAS)2 is the causative pathogen for a diverse collection of human diseases, such as pharyngitis, bacteremia, and necrotizing fasciitis (1). GAS strains produce a variety of pathogenic factors such as streptolysin O (SLO), superantigens, and DNase (2-4). Invasive GAS diseases occur in ϳ1/1000 cases, with associated mortality of 25% (5).Autophagy is defined as "self-eating," bulk degradation system for cytoplasmic components. During autophagy, double membrane structures are formed in the cytoplasm, in which cytoplasmic organelles and proteins are sequestered. These structures, called autophagosomes, subsequently fuse with lysosomes to degrade the components within them. This system is important for the physiological turnover of cytoplasmic components, and is involved in a number of clinical conditions and diseases (6, 7). Recently, we and others showed that GAS is captured and degraded by autophagy, not by the endosomelysosome system (8, 9). Some species of bacteria invade host non-phagocytic cells, such as epithelial cells, and are largely degraded by the endocytosis pathway (10 -12). However, some bacteria, including Listeria monocytogenes, Shigella flexneri, Mycobacterium tuberculosis, and Salmonella typhimurium, cannot be eliminated by endosomes, and replicate within the cytoplasm (13-15). The autophagic machinery is thought to act to remove these bacteria. However, it is still unclear under what circumstances the intracellular bacteria are sequestered by autophagosomes and what events in the infected cells lead to the degradation of bacteria by autophagy.A cholesterol-dependent cytolysin of GAS, SLO, is a homolog of listerio...

No abstract

No abstract