Isolation and characterization of a native avirulent strain of Streptococcus suis serotype 2: a perspective for vaccine development

Abstract

Streptococcus suis, an emerging infectious pathogen, is the cause of two large-scale outbreaks of human streptococcal toxic shock syndrome in China, and has attracted much attention from the scientific community. The genetic basis of its pathogenesis remains enigmatic, and no effective prevention measures have been established. To better understand the virulence differentiation of S. suis and develop a promising vaccine, we isolated and sequenced a native avirulent S. suis strain (05HAS68). Animal experiments revealed that 05HAS68 is an avirulent strain and could protect piglets from the attack of virulent strains. Comparative genomics analyses demonstrated the genetic basis for the lack of virulence in 05HAS68, which is characterized by the absence of some important virulence-associated factors and the intact 89K pathogenicity island. Lack of virulence was also illustrated by reduced survival of 05HAS68 compared to a virulent strain in pig whole blood. Further investigations revealed a large-scale genomic rearrangement in 05HAS68, which was proposed to be mediated by transposase genes and/or prophages. This genomic rearrangement may have caused the genomic diversity of S. suis, and resulted in biological discrepancies between 05HAS68 and highly virulent S. suis strains.

Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28

“…We identified 2,221 CDSs in NSUI002. This is a slightly higher number than found in the very recently finished genome of avirulent ST28 Chinese strain 05HAS68 (2,009 CDSs) [ 13 ]. Most other closed S .…”

“…suis strain 1330 was avirulent in both mice and swine [ 12 ]. More recently, it was shown that an ST28 strain isolated from the tonsils of an asymptomatic pig in China had very low virulence in a swine model of infection [ 13 ]. However, ST28 strains are often isolated from diseased swine in China and Japan [ 14 – 16 ], and at least four human ST28 cases have been reported in Thailand and Japan [ 17 – 19 ].…”

Comparative analysis ofStreptococcusgenomes

“…A consequence of the highly dynamic nature of bacterial genomes is frequent genomic rearrangements. Large inversions across the replication axis, deletions and insertions have been observed in S. pneumoniae (Camilli et al, 2011;Williams et al, 2012), S. suis (Yao et al, 2015;Athey et al, 2015), S. pyogenes (Hamada, Kawabata, and Nakagawa, 2015). The inversions have been suggested to rebalance the chromosomal architecture affected by insertions of large DNA segments (Camilli et al, 2011).…”

The Impact of SsPI-1 Deletion on Streptococcus suis Virulence

“…Vaccines under development are expected to reduce mortality and clinical manifestations of S. suis systemic disease. In a previous experimental study, a native avirulent S. suis strain of serotype 2 isolated from the tonsil of a healthy pig was shown to provide complete protection against a lethal homologous S. suis serotype 2 challenge in piglets [21], which has implications for the development of an efficacious vaccine to fight this important pathogen. Similarly, a good protection was also observed in mice and swine when using another live avirulent S. suis type 2 strain (#1330), which was first isolated from the lung of a pig with pneumonia [32].…”

“…The type IV secretion system (T4SS) encoded at the 5' end of SsPI-1 can not only mediate the conjugal transfer of SsPI-1 [15], but also deliver effectors directly into the host cell, thus causing substantial tissue damage [20]. Furthermore, comparative genomics analyses revealed the complete absence of SsPI-1 in a native avirulent strain 05HAS68, but this strain contains instead, a novel ~113 kb metabolic island in the corresponding position of the genome [21], underscoring again the critical role of SsPI-1 in the pathogenesis of S. suis.…”