Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Positive and negative control mechanisms of pathogenicity expression in Streptococcus intermedius (#68)

Toshifumi Tomoyasu 1 , Atsushi Tabata 1 , Shinya Chiba 1 , Takahiro Yamasaki 1 , Shingo Kusaka 1 , Nozomi Takeda 1 , Masaaki Tamaoka 1 , Kazuto Ohkura 2 , Robert A Whiley 3 , Hideaki Nagamune 1
  1. Tokushima University Graduate School, Minami-josanjima, TOKUSHIMA PREFECTURE, Japan
  2. Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie Prefecture, JAPAN
  3. Department of Clinical and Diagnostic Oral Sciences, Bart’s and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

【Purpose】Streptococcus intermedius (SI) is an opportunistic pathogen secreting a human-specific cytolysin: intermedilysin (ILY) as a major pathogenic factor. The ily expression is suppressed with LacR: the repressor of lac operon, so that galactose (Gal) up-regulates the ily expression. Moreover, SI can degrade glycans into monosaccharides such as Gal and N-acetylneuraminic acid (NeuNAc) using multisubstrate glycosidase A (MsgA) and neuraminidase (NanA). Therefore, we investigated the pathogenicity regulation via sugars in SI.

【Results and Discussion】 We detected ILY-overproduction in SI strain PC574 cultured in fetal bovine serum (FBS) as compared to the standard medium. FBS-cultured cells also showed higher MsgA and NanA activity although ILY-overproduction in FBS was undetectable in mutants nanA-null and msgA-null. In this study, it was revealed that purified MsgA and NanA produced 2.8 mM Gal and 4.3 mM NeuNAc in FBS which were sufficient to up-regulate the expression of ILY, MsgA and NanA. Interestingly, >10 mM Gal strongly inhibited ILY activity. Conversely, no increase of ILY was observed in human plasma, rather it inhibited the stimulation by FBS. We confirmed that human plasma contains immunoglobulins neutralizing ILY, MsgA, and NanA and results in reduction of cytotoxicity in FBS of S. intermedius toward human cell-line, HepG2. Overall, blood contains factors that stimulate and inhibit ILY expression and activity, which affect monosaccharide production. These results suggest that SI is in symbiosis with human on the balance of pathogenicity control mechanisms via mainly sugars and serious failure in negative control induces SI infectious diseases.