contribution of a genomic accessory region encoding a putative cellobiose phosphotransferase system to virulence of streptococcus pneumoniae贡献的基因组辅助区域编码一个假定的纤维二糖磷酸转移酶系统毒性肺炎链球菌.pdfVIP

Contribution of a Genomic Accessory Region Encoding a Putative Cellobiose Phosphotransferase System to Virulence of Streptococcus pneumoniae ¤ Lauren J. McAllister, Abiodun D. Ogunniyi, Uwe H. Stroeher , James C. Paton* Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia Abstract Streptococcus pneumoniae (the pneumococcus) is a formidable human pathogen, responsible for massive global morbidity and mortality. The ability to utilize carbohydrates in a variety of host niches appears to be integral to pneumococcal pathogenesis. In this study we investigated a genomic island, which includes a ROK family protein, a putative cellobiose phosphotransferase system (PTS) and a putative sulfatase. This accessory region is widespread in the pneumococcus in strains of various serotypes and levels of virulence. We have performed simple bioinformatic analysis of the region and investigated its role in vivo in 2 strains with markedly different virulence profiles (WCH206 of serotype 3, ST180; Menzies5 of serotype 11A, ST662). Deleting and replacing the entire island with an antibiotic resistance cassette caused the virulent serotype 3 strain to become attenuated in a murine pneumonia/sepsis model. Further mutants were constructed and used to show that various components of the island contribute significantly to the fitness of WCH206 in a variety of niches of this model, including the nasopharynx, ears and blood, but especially in the lungs. In addition, the island conferred a competitive advantage in nasopharyngeal colonization for the serotype 11A strain, which was essentially avirulent in the pneumoni