Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non‐streptococcal toxic shock syndrome transition in the novel‐type Streptococcus pyogenes isolates that lost a salRK

Abstract

Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Mutations in covR/S or rgg, negative regulators, can reportedly modulate the severity of infection in this pathogen. Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as 'novel-type'). In this study, the two novel 'STSS' isolates 10-85stss and 11-171stss were more virulent than the two novel 'non-STSS' isolates 11O-2non and 11T-3non when examined using a mouse model of invasive infection. Genome-sequencing experiments using the three strains 10-85stss , 11-171stss , and 11O-2non detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2non . Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2non , suggesting that the mutation in fabT, but not in covR/S or rgg, is involved in the differential virulence among the novel-type clinical isolates. This type of non-synonymous fabT mutation was also identified in 12 non-STSS isolates (including 11O-2non and 11T-3non ), and most of those 12 isolates showed impaired FabT function.

Complete Genome Sequence of emm 1 Streptococcus pyogenes 10-85, a Strain Isolated from a Patient with Streptococcal Toxic Shock Syndrome in Japan

“…We observed 1,664 protein-coding regions, 18 rRNA operons, and 67 tRNA genes. The gene content matched the previously reported results (11–14).…”

“…S. pyogenes strain 10-85 from an STSS patient is one of the isolates with the deletion (11), and it contained no mutations in covR , covS , and rgg (12). The strain 10-85 is resistant to macrolide and has a conjugative prophage Φ1207.3 (formerly Tn 1207.3 ), which carries the macrolide resistance genes mef (A) and msr (D) (13, 14).…”

“…The S. pyogenes strain 10-85 genome has been previously sequenced, and a total of 27 contigs were obtained (12). To obtain the complete genome sequence, the strain 10-85 genome was resequenced on a PacBio RS II instrument (Pacific Biosciences, Menlo Park, CA) at TaKaRa Bio, Inc. (Shiga, Japan).…”

Enterococcus faecalis Encodes an Atypical Auxiliary Acyl Carrier Protein Required for Efficient Regulation of Fatty Acid Synthesis by Exogenous Fatty Acids

“…Interestingly, fabT mutants have been reported to arise during streptococcal infections (28, 29). For example, in a massive genomic sequencing study of 2,954 S.…”

FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis

“…GAS infections are also responsible for post-infectious complications such as rheumatic arthritis and glomerulonephritis and, altogether, GAS infections are responsible for 517,000 deaths annually worldwide (6,7). In one study, 74 clinical isolates of the same genotype, from either invasive infections (mainly streptococcal toxic shock syndrome), or non-invasive infections, were analyzed (8). fabT point mutations were only detected in noninvasive infections (2 out of 38 isolates).…”