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The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies

Rumpret, Matevž ; Lannergård, Jonas LU ; Kristensen, Bodil M. LU ; Lynskey, Nicola N. ; Bowen, Connor ; Johnsson, Eskil LU ; Nilsson, Olof R. ; Norrby-Teglund, Anna ; Stålhammar-Carlemalm, Margaretha LU and Lindahl, Gunnar LU , et al. (2026) In EMBO Molecular Medicine 18(8). p.3086-3108
Abstract

Vaccine candidates are typically identified through characterization of microbial surface antigens expressed under laboratory conditions. Here, we studied the major human pathogen Streptococcus pyogenes and showed that Slr, a lipoprotein encoded by all strains, is not detected on the bacterial surface during growth in broth but nevertheless is targeted by protective antibodies in vivo, as demonstrated by passive and active immunizations in a mouse model of invasive infection. The expression of Slr is governed by the zinc-controlled regulator AdcR, indicating that zinc depletion triggers surface expression of Slr in vivo. During infection in humans and mice, the antibody response to Slr is comparable to that elicited by the classical M... (More)

Vaccine candidates are typically identified through characterization of microbial surface antigens expressed under laboratory conditions. Here, we studied the major human pathogen Streptococcus pyogenes and showed that Slr, a lipoprotein encoded by all strains, is not detected on the bacterial surface during growth in broth but nevertheless is targeted by protective antibodies in vivo, as demonstrated by passive and active immunizations in a mouse model of invasive infection. The expression of Slr is governed by the zinc-controlled regulator AdcR, indicating that zinc depletion triggers surface expression of Slr in vivo. During infection in humans and mice, the antibody response to Slr is comparable to that elicited by the classical M protein and is, intriguingly, directed almost exclusively against a region with histidine triad (HT) motifs, an outcome that may represent a mechanism of immune escape. For vaccine development, these data focus interest on Slr and other microbial surface proteins selectively expressed in vivo.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
EMBO Molecular Medicine
volume
18
issue
8
pages
23 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:42298213
  • scopus:105041945967
ISSN
1757-4676
DOI
10.1038/s44321-026-00470-0
language
English
LU publication?
yes
id
76b480c4-23a4-4beb-9d3c-3c8230c8946a
date added to LUP
2026-09-16 14:48:57
date last changed
2026-09-17 03:00:03
@article{76b480c4-23a4-4beb-9d3c-3c8230c8946a,
  abstract     = {{<p>Vaccine candidates are typically identified through characterization of microbial surface antigens expressed under laboratory conditions. Here, we studied the major human pathogen Streptococcus pyogenes and showed that Slr, a lipoprotein encoded by all strains, is not detected on the bacterial surface during growth in broth but nevertheless is targeted by protective antibodies in vivo, as demonstrated by passive and active immunizations in a mouse model of invasive infection. The expression of Slr is governed by the zinc-controlled regulator AdcR, indicating that zinc depletion triggers surface expression of Slr in vivo. During infection in humans and mice, the antibody response to Slr is comparable to that elicited by the classical M protein and is, intriguingly, directed almost exclusively against a region with histidine triad (HT) motifs, an outcome that may represent a mechanism of immune escape. For vaccine development, these data focus interest on Slr and other microbial surface proteins selectively expressed in vivo.</p>}},
  author       = {{Rumpret, Matevž and Lannergård, Jonas and Kristensen, Bodil M. and Lynskey, Nicola N. and Bowen, Connor and Johnsson, Eskil and Nilsson, Olof R. and Norrby-Teglund, Anna and Stålhammar-Carlemalm, Margaretha and Lindahl, Gunnar and McCarthy, Alex J.}},
  issn         = {{1757-4676}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{3086--3108}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{The Slr protein of Streptococcus pyogenes is selectively expressed in vivo and is a target for protective antibodies}},
  url          = {{http://dx.doi.org/10.1038/s44321-026-00470-0}},
  doi          = {{10.1038/s44321-026-00470-0}},
  volume       = {{18}},
  year         = {{2026}},
}