Frontiers in Microbiology (Mar 2022)

The Association Between Onset of Staphylococcal Non-menstrual Toxic Shock Syndrome With Inducibility of Toxic Shock Syndrome Toxin-1 Production

  • Yusuke Taki,
  • Yusuke Taki,
  • Shinya Watanabe,
  • Yusuke Sato’o,
  • Xin-Ee Tan,
  • Hisaya K. Ono,
  • Kotaro Kiga,
  • Yoshifumi Aiba,
  • Teppei Sasahara,
  • Aa Haeruman Azam,
  • Kanate Thitiananpakorn,
  • Srivani Veeranarayanan,
  • Feng-Yu Li,
  • Yuancheng Zhang,
  • Tomofumi Kawaguchi,
  • Sarah Hossain,
  • Maniruzzaman,
  • Dong-Liang Hu,
  • Longzhu Cui

DOI
https://doi.org/10.3389/fmicb.2022.765317
Journal volume & issue
Vol. 13

Abstract

Read online

Non-menstrual toxic shock syndrome (non-mTSS) is a life-threatening disease caused by Staphylococcus aureus strains producing superantigens, such as staphylococcal enterotoxins A, B, C, and toxic shock syndrome toxin-1 (TSST-1). However, little is known about why the TSS cases are rare, although S. aureus strains frequently carry a tst gene, which encodes TSST-1. To answer this question, the amount of TSST-1 produced by 541 clinical isolates was measured in both the presence and absence of serum supplementation to growth media. Then a set of S. aureus strains with similar genetic backgrounds isolated from patients presenting with non-mTSS and those with clinical manifestations other than non-mTSS was compared for their TSST-1 inducibility by human serum, and their whole-genome sequences were determined. Subsequently, the association of mutations identified in the tst promoter of non-mTSS strains with TSST-1 inducibility by human serum was evaluated by constructing promoter replacement mutants and green fluorescent protein (GFP) reporter recombinants. Results showed that 39 out of 541 clinical isolates (7.2%), including strains isolated from non-mTSS patients, had enhanced production of TSST-1 in the presence of serum. TSST-1 inducibility by human serum was more clearly seen in non-mTSS strains of clonal complex (CC)-5. Moreover, the whole-genome sequence analysis identified a set of sequence variations at a putative SarA-binding site of the tst promoter. This sequence variation was proven to be partially responsible for the induction of TSST-1 production by human serum. We conclude that the onset of staphylococcal toxic shock syndrome caused by TSST-1-producing CC-5 strains seem at least partially initiated by serum induction of TSST-1, which is regulated by the mutation of putative SarA-binding site at the tst promoter.

Keywords