Streptococcal Pyrogenic Exotoxin F (SpeF) Causes Permeabilization of Lung Blood Vessels

Abstract

Acute respiration distress syndrome (ARDS) is a typical complication in toxic shock-like syndrome (TSLS) caused byStreptococcus pyogenes. An isolated perfused rat lung model was used to identify the causative agent of ARDS in TSLS in this study. Some crude preparations separated from the culture supernatants ofS. pyogenes isolates caused rapid increases in the weight of perfused lungs, indicating vascular permeabilization. Six samples from M type 1 and 3 isolates from TSLS and pharyngitis patients showed strong permeabilization activity, whereas preparations from isolates of other M types (although the number of isolates examined was limited) were negative. The active substance was purified to a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using various columns, and the N-terminal amino acid sequence was determined. The resultant sequence of eight amino acids was identical to SpeF (mitogenic factor). Moreover, the vascular permeabilization activity of the purified band was abolished with anti-SpeF antiserum prepared by immunizing with the purified SpeF. This activity was also neutralized by the antiserum prepared by immunizing with a synthetic peptide derived from the published SpeF sequence. These results suggested that streptococcal SpeF is a major cause of permeabilization of lung blood vessels and sufficient for the pathogenesis of ARDS under the conditions of TSLS caused by S. pyogenes.

Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases

“…SpeB can promote the spread of bacteria and their products in host tissues by degrading the tissue structure and can also degrade proteins and antimicrobial peptide LL-37 in order to resist immunity ( Walker et al, 2014 ). SpeF is the main cause of pulmonary vascular permeability, which is sufficient to cause acute respiratory distress syndrome under the conditions of toxic shock-like syndrome caused by S. pyogenes ( Matsumoto et al, 1999 ). Among all virulence factors, SAg is of particular concern.…”

Post‐proteomic identification of a novel phage‐encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes

“…It was suggested that they help bacterial spreading by liquefying pus (Tillet et al ., 1948) and that, being mostly phage‐encoded, they may help the induced phages to digest the DNA released during bacterial lysis (Broudy et al ., 2002). One of the best‐characterized streptodornases, DNase B (also known as mitogenic factor, MF, or SpeF), causes permeabilization of lung blood vessels as a complication of toxic shock‐like syndrome (Matsumoto et al ., 1999). Besides DNase B, four GAS proteins with DNase activity have been identified: streptodornase D (SdaD) (Podbielski et al ., 1996), Sdα (Hasegawa et al ., 2002a), mitogenic factor 2 (MF2) or Spd1 (Broudy et al ., 2002), and mitogenic factor 3 (MF3) or Spd3 (Hasegawa et al ., 2002b).…”

Close Correlation of Streptococcal DNase B (sdaB) Alleles with emm Genotypes in Streptococcus pyogenes

“…This was confirmed by western blot analysis with DNase Bspecific antibodies. Western blot analysis was performed as described previously (4) and band intensity of the DNase B protein was measured by an ImageMaster Labscan version 3.00 (Amersham Biosciences Corp., Piscataway, N.J., U.S.A.). DNase B proteins were detected at similar levels of amount in the culture of these strains except the DNase B3 strain (Fig.…”

“…of strains) sdaB allele (No. of strains) 1 (9) sdaB6 (9) 2 (8) sdaB7 (8) 3 (7) sdaB2 (7) 4 (8) sdaB7 (8) 6 (8) sdaB1 (8) 11 (5) sdaB3 (1) sdaB8 (4) 12 (7) sdaB9 (7) 18 (5) sdaB10 (5) 22 (6) sdaB11 (6) 28 (7) sdaB4 (1) sdaB12 (6) 50/62 (1) sdaB13 (1) 87 (1) sdaB5 (1) 89 (5) sdaB14 (5) 94 (6) sdaB15 (6) (83) The protein preparations precipitated with final 10% trichloroacetic acid from each volume of the culture supernatant shown in the left side were subjected to SDS-PAGE and then blotted onto a nitrocellulose membrane and detected with the anti-DNase B serum as described previously (4). Lanes 1 to 3: the protein preparations from emm3 strains with DNase B2, respectively; Lane 4: the protein preparation from an emm11 strain with DNase B3; Lane 5: the protein preparation from an emm28 strain with DNase B4.…”